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  1. Mutual information reveals multiple structural relaxation mechanisms in a model glass former.

    Science.gov (United States)

    Dunleavy, Andrew J; Wiesner, Karoline; Yamamoto, Ryoichi; Royall, C Patrick

    2015-01-22

    Among the key challenges to our understanding of solidification in the glass transition is that it is accompanied by little apparent change in structure. Recently, geometric motifs have been identified in glassy liquids, but a causal link between these motifs and solidification remains elusive. One 'smoking gun' for such a link would be identical scaling of structural and dynamic lengthscales on approaching the glass transition, but this is highly controversial. Here we introduce an information theoretic approach to determine correlations in displacement for particle relaxation encoded in the initial configuration of a glass-forming liquid. We uncover two populations of particles, one inclined to relax quickly, the other slowly. Each population is correlated with local density and geometric motifs. Our analysis further reveals a dynamic lengthscale similar to that associated with structural properties, which may resolve the discrepancy between structural and dynamic lengthscales.

  2. Kinetic Models of Cyclosporin A in Polar and Apolar Environments Reveal Multiple Congruent Conformational States.

    Science.gov (United States)

    Witek, Jagna; Keller, Bettina G; Blatter, Markus; Meissner, Axel; Wagner, Trixie; Riniker, Sereina

    2016-08-22

    The membrane permeability of cyclic peptides and peptidomimetics, which are generally larger and more complex than typical drug molecules, is likely strongly influenced by the conformational behavior of these compounds in polar and apolar environments. The size and complexity of peptides often limit their bioavailability, but there are known examples of peptide natural products such as cyclosporin A (CsA) that can cross cell membranes by passive diffusion. CsA is an undecapeptide with seven methylated backbone amides. Its crystal structure shows a "closed" twisted β-pleated sheet conformation with four intramolecular hydrogen bonds that is also observed in NMR measurements of CsA in chloroform. When binding to its target cyclophilin, on the other hand, CsA adopts an "open" conformation without intramolecular hydrogen bonds. In this study, we attempted to sample the complete conformational space of CsA in chloroform and in water by molecular dynamics simulations in order to better understand its conformational behavior in these two environments and to rationalize the good membrane permeability of CsA observed experimentally. From 10 μs molecular dynamics simulations in each solvent, Markov state models were constructed to characterize the metastable conformational states. The model in chloroform is compared to nuclear Overhauser effect NMR spectroscopy data reported in this study and taken from the literature. The conformational landscapes in the two solvents show significant overlap but also clearly distinct features.

  3. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

    NARCIS (Netherlands)

    M. Noga (Marek); A. Dane (Adrie); S. Shi (Shanna); A. Attali (Amos); H. van Aken (Hans); E. Suidgeest (Ernst); T. Tuinstra (Tinka); B. Muilwijk (Bas); L. Coulier (Leon); T.M. Luider (Theo); R.M. Reijmers (Rogier); R. Vreeken (Rob); T. Hankemeier (Thomas)

    2012-01-01

    textabstractExperimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC-MS and GC-MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein

  4. An integrated model of multiple-condition ChIP-Seq data reveals predeterminants of Cdx2 binding.

    Directory of Open Access Journals (Sweden)

    Shaun Mahony

    2014-03-01

    Full Text Available Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.

  5. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  6. A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model.

    Science.gov (United States)

    Rudd, Danielle S; Axelsen, Michael; Epping, Eric A; Andreasen, Nancy C; Wassink, Thomas H

    2014-12-01

    Schizophrenia is a chronic and severe psychiatric disorder that is highly heritable. While both common and rare genetic variants contribute to disease risk, many questions still remain about disease etiology. We performed a genome-wide analysis of copy number variants (CNVs) in 166 schizophrenia subjects and 52 psychiatrically healthy controls. First, overall CNV characteristics were compared between cases and controls. The only statistically significant finding was that deletions comprised a greater proportion of CNVs in cases. High interest CNVs were then identified as conservative using the following filtering criteria: (i) known deleterious CNVs; (ii) CNVs > 1 Mb that were novel (not found in a database of control individuals); and (iii) CNVs 1 Mb) or with multiple conservative CNVs. Two case individuals with the highest burden of conservative CNVs also share a recurrent 15q11.2 BP1-2 deletion, indicating a role for a potential multiple-hit CNV model for schizophrenia. In total, we report three 15q11.2 BP1-2 deletion individuals with schizophrenia, adding to a growing body of evidence that this CNV is involved in disease etiology.

  7. A Quantitative Model of Motility Reveals Low-Dimensional Variation in Exploratory Behavior Across Multiple Nematode Species

    Science.gov (United States)

    Helms, Stephen; Avery, Leon; Stephens, Greg; Shimizu, Tom

    2014-03-01

    Animal behavior emerges from many layers of biological organization--from molecular signaling pathways and neuronal networks to mechanical outputs of muscles. In principle, the large number of interconnected variables at each of these layers could imply dynamics that are complex and hard to control or even tinker with. Yet, for organisms to survive in a competitive, ever-changing environment, behavior must readily adapt. We applied quantitative modeling to identify important aspects of behavior in chromadorean nematodes ranging from the lab strain C. elegans N2 to wild strains and distant species. We revealed subtle yet important features such as speed control and heavy-tailed directional changes. We found that the parameters describing this behavioral model varied among individuals and across species in a correlated way that is consistent with a trade-off between exploratory and exploitative behavior.

  8. Modeling human retinal development with patient-specific induced pluripotent stem cells reveals multiple roles for visual system homeobox 2.

    Science.gov (United States)

    Phillips, M Joseph; Perez, Enio T; Martin, Jessica M; Reshel, Samantha T; Wallace, Kyle A; Capowski, Elizabeth E; Singh, Ruchira; Wright, Lynda S; Clark, Eric M; Barney, Patrick M; Stewart, Ron; Dickerson, Sarah J; Miller, Michael J; Percin, E Ferda; Thomson, James A; Gamm, David M

    2014-06-01

    Human induced pluripotent stem cells (hiPSCs) have been shown to differentiate along the retinal lineage in a manner that mimics normal mammalian development. Under certain culture conditions, hiPSCs form optic vesicle-like structures (OVs), which contain proliferating progenitors capable of yielding all neural retina (NR) cell types over time. Such observations imply conserved roles for regulators of retinogenesis in hiPSC-derived cultures and the developing embryo. However, whether and to what extent this assumption holds true has remained largely uninvestigated. We examined the role of a key NR transcription factor, visual system homeobox 2 (VSX2), using hiPSCs derived from a patient with microphthalmia caused by an R200Q mutation in the VSX2 homeodomain region. No differences were noted between (R200Q)VSX2 and sibling control hiPSCs prior to OV generation. Thereafter, (R200Q)VSX2 hiPSC-OVs displayed a significant growth deficit compared to control hiPSC-OVs, as well as increased production of retinal pigmented epithelium at the expense of NR cell derivatives. Furthermore, (R200Q)VSX2 hiPSC-OVs failed to produce bipolar cells, a distinctive feature previously observed in Vsx2 mutant mice. (R200Q)VSX2 hiPSC-OVs also demonstrated delayed photoreceptor maturation, which could be overcome via exogenous expression of wild-type VSX2 at early stages of retinal differentiation. Finally, RNAseq analysis on isolated hiPSC-OVs implicated key transcription factors and extracellular signaling pathways as potential downstream effectors of VSX2-mediated gene regulation. Our results establish hiPSC-OVs as versatile model systems to study retinal development at stages not previously accessible in humans and support the bona fide nature of hiPSC-OV-derived retinal progeny.

  9. Phylogeographic analysis and environmental niche modeling of widespread shrub Rhododendron simsii in China reveals multiple glacial refugia during the last glacial maximum

    Institute of Scientific and Technical Information of China (English)

    Yong LI; Hai-Fei YAN; Xue-Jun GE

    2012-01-01

    The phylogeography of common and widespread species can help us to understand the history of local flora and vegetation.Here,we study the semi-evergreen shrub Rhododendron simsii Planch.,which is found in most areas of current evergreen broad leaved forest in China.Two noncoding chloroplast DNA (cpDNA) regions(rpl20-rps12 and trnL-F) and three amplified fragment length polymorphism (AFLP) primer sets (E-AAC/M-CTA,E-AGC/M-CTA and E-AGG/M-CAT) were used to examine the phylogeographic pattern in relation to past (last glacial maximum) and present distributions based on ecological niche modeling.The cpDNA data revealed four phylogeographic groups (East,South,West,and North groups) corresponding to geographic regions.Molecular dating suggests that lineage diversification within species likely occurred during the mid-to-late Pleistocene.In contrast,the four main cpDNA phylogeographic groups were not supported by the AFLP dataset.The highest likelihood of the AFLP data was obtained when samples were clustered into three groups (K =3).However,these groupings did not correspond to separate geographic regions supported by cpDNA data.Both mismatch distribution analysis and environmental niche modeling (ENM) indicated that multiple glacial refugia were maintained across the range of Rhododendron simsii during the last glacial maximum,contrary to the previous hypothesis that subtropical broad leaved evergreen forests were forced to retreat southward as far as 25°N.The discordance between the patterns revealed by cpDNA and AFLP data indicate that localized postglacial range expansions may facilitate extensive gene flow between the major glacial refugia.

  10. Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

    Directory of Open Access Journals (Sweden)

    Risa Shiraishi

    Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

  11. Behavioural mapping of a pelagic seabird: combining multiple sensors and a hidden Markov model reveals the distribution of at-sea behaviour.

    Science.gov (United States)

    Dean, Ben

    2013-01-06

    The use of miniature data loggers is rapidly increasing our understanding of the movements and habitat preferences of pelagic seabirds. However, objectively interpreting behavioural information from the large volumes of highly detailed data collected by such devices can be challenging. We combined three biologging technologies—global positioning system (GPS), saltwater immersion and time–depth recorders—to build a detailed picture of the at-sea behaviour of the Manx shearwater (Puffinus puffinus) during the breeding season. We used a hidden Markov model to explore discrete states within the combined GPS and immersion data, and found that behaviour could be organized into three principal activities representing (i) sustained direct flight, (ii) sitting on the sea surface, and (iii) foraging, comprising tortuous flight interspersed with periods of immersion. The additional logger data verified that the foraging activity corresponded well to the occurrence of diving. Applying this approach to a large tracking dataset revealed that birds from two different colonies foraged in local waters that were exclusive, but overlapped in one key area: the Irish Sea Front (ISF). We show that the allocation of time to each activity differed between colonies, with birds breeding furthest from the ISF spending the greatest proportion of time engaged in direct flight and the smallest proportion of time engaged in foraging activity. This type of analysis has considerable potential for application in future biologging studies and in other taxa.

  12. Multiplicative LSTM for sequence modelling

    OpenAIRE

    Krause, Ben; Lu, Liang; Murray, Iain; Renals, Steve

    2016-01-01

    This paper introduces multiplicative LSTM, a novel hybrid recurrent neural network architecture for sequence modelling that combines the long short-term memory (LSTM) and multiplicative recurrent neural network architectures. Multiplicative LSTM is motivated by its flexibility to have very different recurrent transition functions for each possible input, which we argue helps make it more expressive in autoregressive density estimation. We show empirically that multiplicative LSTM outperforms ...

  13. Multiplicity description by gluon model

    CERN Document Server

    Kokoulina, E S

    2015-01-01

    Study of high multiplicity events in proton-proton interactions is carried out at the U-70 accelerator (IHEP, Protvino). These events are extremely rare. Usually, Monte Carlo codes underestimate topological cross sections in this region. The gluon dominance model (GDM) was offered to describe them. It is based on QCD and a phenomenological scheme of a hadronization stage. This model indicates a recombination mechanism of hadronization and a gluon fission. Future program of the SVD Collaboration is aimed at studying a long-standing puzzle of excess soft photon yield and its connection with high multiplicity at the U-70 and Nuclotron facility at JINR, Dubna.

  14. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  15. Multiple Model Approaches to Modelling and Control,

    DEFF Research Database (Denmark)

    Why Multiple Models?This book presents a variety of approaches which produce complex models or controllers by piecing together a number of simpler subsystems. Thisdivide-and-conquer strategy is a long-standing and general way of copingwith complexity in engineering systems, nature and human probl...

  16. Experimental study of a multiplicative model of multiple ionospheric reflections

    Science.gov (United States)

    Mirkotan, S. F.; Zhuravlev, S. V.; Kosovtsov, Iu. N.

    1983-04-01

    An important parameter of a partially scattered ionospheric signal is the signal-noise energy parameter beta. A new method for determining beta sub n (where n is the multiplicity of reflection) has been proposed on the basis of the statistical multiplicative model of Mirkotan et al. (1981, 1982). This paper describes an experimental verification of the proposed method; data on beta sub n obtained by the traditional method and by the new method are compared. In addition, the validity of the multiplicative model is evaluated, and features of the mechanism responsible for the multiple scattering of an ionospheric signal are examined.

  17. In vivo models of multiple myeloma (MM).

    Science.gov (United States)

    Sanchez, Eric; Chen, Haiming; Berenson, James R

    2014-06-01

    The development of the plasma cell tumor (PCT) model was the first widely accepted in vivo model of multiple myeloma (MM). Potter and colleagues used this chemically induced PCT model to study the pathophysiology of malignant plasma cells and also used it to screen anti-MM agents. Two decades later the C57BL/KaLwRij mouse strain was found to spontaneously develop MM. Testing of pamidronate using this endogenously arising MM model revealed significant reductions in MM-associated bone disease, which was subsequently confirmed in human trials in MM patients. Transgenic models have also been developed in which the MM is localized in the bone marrow causing lytic bone lesions. Experiments in a transgenic model showed that a new oral proteasome inhibitor was effective at reducing MM burden. A clinical trial later confirmed this observation and validated the model. The xenograft model has been used to grow human MM in immunocompromised mice. The xenograft models of MM have been very useful in optimizing drug schedules and doses, which have helped in the treatments given to MM patients. However, in vivo models have been criticized for having a low clinical predictive power of new chemical entities (NCEs). Despite this, the knowledge gained from in vivo models of MM has without a doubt benefited MM patients.

  18. Genesis of tropical cyclone Nargis revealed by multiple satellite observations

    Science.gov (United States)

    Kikuchi, Kazuyoshi; Wang, Bin; Fudeyasu, Hironori

    2009-03-01

    Tropical cyclone (TC) Nargis recently battered Myanmar on May 2 2008 is one of the most deadly tropical storms in history. Nargis was initiated by an abnormally strong intraseasonal westerly event associated with Madden-Julian oscillation (MJO) in the eastern Indian Ocean. An incipient cyclonic disturbance emerged as an emanation of Rossby wave-induced vortex when the intraseasonal convective anomaly reached the Maritime Continent. The northeastward movement of MJO convection facilitated further development of the disturbance. The incipient disturbance became a tropical disturbance (TD) with a central warm-core structure on April 26. The further development from the TD to TC formation on April 28 is characterized by two distinctive stages: a radial contraction followed by a rapid intensification. The processes responsible for contraction and rapid intensification are discussed by diagnosis of multiple satellite data. This proposed new scenario is instrumental for understanding how a major TC develops in the northern Indian Ocean.

  19. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    Science.gov (United States)

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  20. Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement

    Directory of Open Access Journals (Sweden)

    Aicha Slassi Sennou

    2014-01-01

    Full Text Available Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day. This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.

  1. Multiple scattering Model in GEANT4

    CERN Document Server

    Urbàn, L

    2002-01-01

    We present a new multiple scattering (MSC) model to simulate the multiple scattering of charged particles in matter. This model does not use the Moliere formalism, it is based on the more complete Lewis theory. The model simulates the scattering of the particle after a given step, computes the path length correction and the lateral displacement as well.

  2. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  3. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    An array of epidemiological results and databases on test animal indicate that risk of cancer and atherosclerosis can be up- or down-regulated by diet through a range of 200%. Other factors contribute incrementally and include the natural terrestrial environment and various human activities that jointly produce complex exposures to endotoxin-producing microorganisms, ionizing radiations, and chemicals. Ordinary personal habits and simple physical irritants have been demonstrated to affect the immune response and risk of disease. There tends to be poor statistical correlation of long-term risk with single agent exposures incurred throughout working careers. However, Agency recommendations for control of hazardous exposures to humans has been substance-specific instead of contextually realistic even though there is consistent evidence for common mechanisms of toxicological and carcinogenic action. That behavior seems to be best explained by molecular stresses from cellular oxygen metabolism and phagocytosis of antigenic invasion as well as breakdown of normal metabolic compounds associated with homeostatic- and injury-related renewal of cells. There is continually mounting evidence that marrow stroma, comprised largely of monocyte-macrophages and fibroblasts, is important to phagocytic and cytokinetic response, but the complex action of the immune process is difficult to infer from first-principle logic or biomarkers of toxic injury. The many diverse database studies all seem to implicate two important processes, i.e., the univalent reduction of molecular oxygen and breakdown of aginuine, an amino acid, by hydrolysis or digestion of protein which is attendant to normal antigen-antibody action. This behavior indicates that protection guidelines and risk coefficients should be context dependent to include reference considerations of the composite action of parameters that mediate oxygen metabolism. A logic of this type permits the realistic common-scale modeling of

  4. Multiple Imputation Strategies for Multiple Group Structural Equation Models

    Science.gov (United States)

    Enders, Craig K.; Gottschall, Amanda C.

    2011-01-01

    Although structural equation modeling software packages use maximum likelihood estimation by default, there are situations where one might prefer to use multiple imputation to handle missing data rather than maximum likelihood estimation (e.g., when incorporating auxiliary variables). The selection of variables is one of the nuances associated…

  5. Dynamical modelling of coordinated multiple robot systems

    Science.gov (United States)

    Hayati, Samad

    1987-01-01

    The state of the art in the modeling of the dynamics of coordinated multiple robot manipulators is summarized and various problems related to this subject are discussed. It is recognized that dynamics modeling is a component used in the design of controllers for multiple cooperating robots. As such, the discussion addresses some problems related to the control of multiple robots. The techniques used to date in the modeling of closed kinematic chains are summarized. Various efforts made to date for the control of coordinated multiple manipulators is summarized.

  6. Massive parallel IGHV gene sequencing reveals a germinal center pathway in origins of human multiple myeloma.

    Science.gov (United States)

    Cowan, Graeme; Weston-Bell, Nicola J; Bryant, Dean; Seckinger, Anja; Hose, Dirk; Zojer, Niklas; Sahota, Surinder S

    2015-05-30

    Human multiple myeloma (MM) is characterized by accumulation of malignant terminally differentiated plasma cells (PCs) in the bone marrow (BM), raising the question when during maturation neoplastic transformation begins. Immunoglobulin IGHV genes carry imprints of clonal tumor history, delineating somatic hypermutation (SHM) events that generally occur in the germinal center (GC). Here, we examine MM-derived IGHV genes using massive parallel deep sequencing, comparing them with profiles in normal BM PCs. In 4/4 presentation IgG MM, monoclonal tumor-derived IGHV sequences revealed significant evidence for intraclonal variation (ICV) in mutation patterns. IGHV sequences of 2/2 normal PC IgG populations revealed dominant oligoclonal expansions, each expansion also displaying mutational ICV. Clonal expansions in MM and in normal BM PCs reveal common IGHV features. In such MM, the data fit a model of tumor origins in which neoplastic transformation is initiated in a GC B-cell committed to terminal differentiation but still targeted by on-going SHM. Strikingly, the data parallel IGHV clonal sequences in some monoclonal gammopathy of undetermined significance (MGUS) known to display on-going SHM imprints. Since MGUS generally precedes MM, these data suggest origins of MGUS and MM with IGHV gene mutational ICV from the same GC B-cell, arising via a distinctive pathway.

  7. Multiplicity Control in Structural Equation Modeling

    Science.gov (United States)

    Cribbie, Robert A.

    2007-01-01

    Researchers conducting structural equation modeling analyses rarely, if ever, control for the inflated probability of Type I errors when evaluating the statistical significance of multiple parameters in a model. In this study, the Type I error control, power and true model rates of famsilywise and false discovery rate controlling procedures were…

  8. Multiple Model Approaches to Modelling and Control,

    DEFF Research Database (Denmark)

    on the ease with which prior knowledge can be incorporated. It is interesting to note that researchers in Control Theory, Neural Networks,Statistics, Artificial Intelligence and Fuzzy Logic have more or less independently developed very similar modelling methods, calling them Local ModelNetworks, Operating...... of introduction of existing knowledge, as well as the ease of model interpretation. This book attempts to outlinemuch of the common ground between the various approaches, encouraging the transfer of ideas.Recent progress in algorithms and analysis is presented, with constructive algorithms for automated model...

  9. Mapping vulnerability of multiple aquifers using multiple models and fuzzy logic to objectively derive model structures.

    Science.gov (United States)

    Nadiri, Ata Allah; Sedghi, Zahra; Khatibi, Rahman; Gharekhani, Maryam

    2017-09-01

    Driven by contamination risks, mapping Vulnerability Indices (VI) of multiple aquifers (both unconfined and confined) is investigated by integrating the basic DRASTIC framework with multiple models overarched by Artificial Neural Networks (ANN). The DRASTIC framework is a proactive tool to assess VI values using the data from the hydrosphere, lithosphere and anthroposphere. However, a research case arises for the application of multiple models on the ground of poor determination coefficients between the VI values and non-point anthropogenic contaminants. The paper formulates SCFL models, which are derived from the multiple model philosophy of Supervised Committee (SC) machines and Fuzzy Logic (FL) and hence SCFL as their integration. The Fuzzy Logic-based (FL) models include: Sugeno Fuzzy Logic (SFL), Mamdani Fuzzy Logic (MFL), Larsen Fuzzy Logic (LFL) models. The basic DRASTIC framework uses prescribed rating and weighting values based on expert judgment but the four FL-based models (SFL, MFL, LFL and SCFL) derive their values as per internal strategy within these models. The paper reports that FL and multiple models improve considerably on the correlation between the modeled vulnerability indices and observed nitrate-N values and as such it provides evidence that the SCFL multiple models can be an alternative to the basic framework even for multiple aquifers. The study area with multiple aquifers is in Varzeqan plain, East Azerbaijan, northwest Iran. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Phylogeography of the widespread African puff adder (Bitis arietans) reveals multiple Pleistocene refugia in southern Africa.

    Science.gov (United States)

    Barlow, Axel; Baker, Karis; Hendry, Catriona R; Peppin, Lindsay; Phelps, Tony; Tolley, Krystal A; Wüster, Catharine E; Wüster, Wolfgang

    2013-02-01

    Evidence from numerous Pan-African savannah mammals indicates that open-habitat refugia existed in Africa during the Pleistocene, isolated by expanding tropical forests during warm and humid interglacial periods. However, comparative data from other taxonomic groups are currently lacking. We present a phylogeographic investigation of the African puff adder (Bitis arietans), a snake that occurs in open-habitat formations throughout sub-Saharan Africa. Multiple parapatric mitochondrial clades occur across the current distribution of B. arietans, including a widespread southern African clade that is subdivided into four separate clades. We investigated the historical processes responsible for generating these phylogeographic patterns in southern Africa using species distribution modelling and genetic approaches. Our results show that interior regions of South Africa became largely inhospitable for B. arietans during glacial maxima, whereas coastal and more northerly areas remained habitable. This corresponds well with the locations of refugia inferred from mitochondrial data using a continuous phylogeographic diffusion model. Analysis of data from five anonymous nuclear loci revealed broadly similar patterns to mtDNA. Secondary admixture was detected between previously isolated refugial populations. In some cases, this is limited to individuals occurring near mitochondrial clade contact zones, but in other cases, more extensive admixture is evident. Overall, our study reveals a complex history of refugial isolation and secondary expansion for puff adders and a mosaic of isolated refugia in southern Africa. We also identify key differences between the processes that drove isolation in B. arietans and those hypothesized for sympatric savannah mammals.

  11. Multiplicative earthquake likelihood models incorporating strain rates

    Science.gov (United States)

    Rhoades, D. A.; Christophersen, A.; Gerstenberger, M. C.

    2017-01-01

    SUMMARYWe examine the potential for strain-rate variables to improve long-term earthquake likelihood models. We derive a set of multiplicative hybrid earthquake likelihood models in which cell rates in a spatially uniform baseline model are scaled using combinations of covariates derived from earthquake catalogue data, fault data, and strain-rates for the New Zealand region. Three components of the strain rate estimated from GPS data over the period 1991-2011 are considered: the shear, rotational and dilatational strain rates. The hybrid model parameters are optimised for earthquakes of M 5 and greater over the period 1987-2006 and tested on earthquakes from the period 2012-2015, which is independent of the strain rate estimates. The shear strain rate is overall the most informative individual covariate, as indicated by Molchan error diagrams as well as multiplicative modelling. Most models including strain rates are significantly more informative than the best models excluding strain rates in both the fitting and testing period. A hybrid that combines the shear and dilatational strain rates with a smoothed seismicity covariate is the most informative model in the fitting period, and a simpler model without the dilatational strain rate is the most informative in the testing period. These results have implications for probabilistic seismic hazard analysis and can be used to improve the background model component of medium-term and short-term earthquake forecasting models.

  12. Discrete choice models with multiplicative error terms

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Bierlaire, Michel

    2009-01-01

    differences. We develop some properties of this type of model and show that in several cases the change from an additive to a multiplicative formulation, maintaining a specification of V, may lead to a large improvement in fit, sometimes larger than that gained from introducing random coefficients in V....

  13. A Multiple Model Approach to Modeling Based on LPF Algorithm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Input-output data fitting methods are often used for unknown-structure nonlinear system modeling. Based on model-on-demand tactics, a multiple model approach to modeling for nonlinear systems is presented. The basic idea is to find out, from vast historical system input-output data sets, some data sets matching with the current working point, then to develop a local model using Local Polynomial Fitting (LPF) algorithm. With the change of working points, multiple local models are built, which realize the exact modeling for the global system. By comparing to other methods, the simulation results show good performance for its simple, effective and reliable estimation.``

  14. Multiple models adaptive feedforward decoupling controller

    Institute of Scientific and Technical Information of China (English)

    Wang Xin; Li Shaoyuan; Wang Zhongjie

    2005-01-01

    When the parameters of the system change abruptly, a new multivariable adaptive feedforward decoupling controller using multiple models is presented to improve the transient response. The system models are composed of multiple fixed models, one free-running adaptive model and one re-initialized adaptive model. The fixed models are used to provide initial control to the process. The re-initialized adaptive model can be reinitialized as the selected model to improve the adaptation speed. The free-running adaptive controller is added to guarantee the overall system stability. At each instant, the best system model is selected according to the switching index and the corresponding controller is designed. During the controller design, the interaction is viewed as the measurable disturbance and eliminated by the choice of the weighting polynomial matrix. It not only eliminates the steady-state error but also decouples the system dynamically. The global convergence is obtained and several simulation examples are presented to illustrate the effectiveness of the proposed controller.

  15. Realistic face modeling based on multiple deformations

    Institute of Scientific and Technical Information of China (English)

    GONG Xun; WANG Guo-yin

    2007-01-01

    On the basis of the assumption that the human face belongs to a linear class, a multiple-deformation model is proposed to recover face shape from a few points on a single 2D image. Compared to the conventional methods, this study has the following advantages. First, the proposed modified 3D sparse deforming model is a noniterative approach that can compute global translation efficiently and accurately. Subsequently, the overfitting problem can be alleviated based on the proposed multiple deformation model. Finally, by keeping the main features, the texture generated is realistic. The comparison results show that this novel method outperforms the existing methods by using ground truth data and that realistic 3D faces can be recovered efficiently from a single photograph.

  16. Comparisons of Caenorhabditis Fucosyltransferase Mutants Reveal a Multiplicity of Isomeric N-Glycan Structures.

    Science.gov (United States)

    Yan, Shi; Jin, Chunsheng; Wilson, Iain B H; Paschinger, Katharina

    2015-12-01

    Recent studies have shown a remarkable degree of plasticity in the N-glycome of the model nematode Caenorhabditis elegans; ablation of glycosylation-relevant genes can result in radically altered N-glycan profiles despite only minor biological phenotypic effects. Up to four fucose residues and five different linkages of fucose are known on the N-glycans of C. elegans. Due to the complexity in the wild type, we established three mutant strains defective in two core fucosyltransferases each (fut-1;fut-6, fut-1;fut-8, and fut-6;fut-8). Enzymatically released N-glycans were subject to HPLC and MALDI-TOF MS/MS, in combination with various treatments, to verify structural details. The N-glycome of the fut-1;fut-6 mutant was the most complex of the three double-mutant strains due to the extension of the core α1,6-fucose as well as the presence of fucose on the bisecting galactose. In contrast, maximally two fucoses were found on N-glycans of the fut-1;fut-8 and fut-6;fut-8 strains. The different locations and capping of fucose meant that up to 13 isomeric structures, many highly galactosylated, were determined for some single masses. These data not only show the high variability of the N-glycomic capacity of a "simple" nematode but also exemplify the need for multiple approaches to reveal individual glycan structures within complex invertebrate glycomes.

  17. Model for Dynamic Multiple of CPPI Strategy

    Directory of Open Access Journals (Sweden)

    Guangyuan Xing

    2014-01-01

    Full Text Available Focusing on the parameter “Multiple” of CPPI strategy, this study proposes a dynamic setting model of multiple for gap risk management purpose. First, CPPI gap risk is measured as the probability that the value loss of active asset exceeds its allowed maximum drop determined by a given multiple setting. Moreover, according to the statistical estimation using SV-EVT approach, a dynamic choice of multiple is detailed as a function of time-varying asset volatility, expected loss, and the possibility of occurrence of extreme events in the active asset returns illustrated empirically on Shanghai composite index data. This study not only enriches the literature of dynamic proportion portfolio insurance, but also provides a practical reference for CPPI investors to choose a moderate risky exposure achieving gap risk management, which promotes CPPI’s application in emerging capital market.

  18. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    Science.gov (United States)

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  19. Variable bit rate video traffic modeling by multiplicative multifractal model

    Institute of Scientific and Technical Information of China (English)

    Huang Xiaodong; Zhou Yuanhua; Zhang Rongfu

    2006-01-01

    Multiplicative multifractal process could well model video traffic. The multiplier distributions in the multiplicative multifractal model for video traffic are investigated and it is found that Gaussian is not suitable for describing the multipliers on the small time scales. A new statistical distribution-symmetric Pareto distribution is introduced. It is applied instead of Gaussian for the multipliers on those scales. Based on that, the algorithm is updated so that symmetric pareto distribution and Gaussian distribution are used to model video traffic but on different time scales. The simulation results demonstrate that the algorithm could model video traffic more accurately.

  20. Application of Multiple Evaluation Models in Brazil

    Directory of Open Access Journals (Sweden)

    Rafael Victal Saliba

    2008-07-01

    Full Text Available Based on two different samples, this article tests the performance of a number of Value Drivers commonly used for evaluating companies by finance practitioners, through simple regression models of cross-section type which estimate the parameters associated to each Value Driver, denominated Market Multiples. We are able to diagnose the behavior of several multiples in the period 1994-2004, with an outlook also on the particularities of the economic activities performed by the sample companies (and their impacts on the performance through a subsequent analysis with segregation of companies in the sample by sectors. Extrapolating simple multiples evaluation standards from analysts of the main financial institutions in Brazil, we find that adjusting the ratio formulation to allow for an intercept does not provide satisfactory results in terms of pricing errors reduction. Results found, in spite of evidencing certain relative and absolute superiority among the multiples, may not be generically representative, given samples limitation.

  1. Incremental activity modeling in multiple disjoint cameras.

    Science.gov (United States)

    Loy, Chen Change; Xiang, Tao; Gong, Shaogang

    2012-09-01

    Activity modeling and unusual event detection in a network of cameras is challenging, particularly when the camera views are not overlapped. We show that it is possible to detect unusual events in multiple disjoint cameras as context-incoherent patterns through incremental learning of time delayed dependencies between distributed local activities observed within and across camera views. Specifically, we model multicamera activities using a Time Delayed Probabilistic Graphical Model (TD-PGM) with different nodes representing activities in different decomposed regions from different views and the directed links between nodes encoding their time delayed dependencies. To deal with visual context changes, we formulate a novel incremental learning method for modeling time delayed dependencies that change over time. We validate the effectiveness of the proposed approach using a synthetic data set and videos captured from a camera network installed at a busy underground station.

  2. Phylogenomic and structural modeling analyses of the PsbP superfamily reveal multiple small segment additions in the evolution of photosystem II-associated PsbP protein in green plants.

    Science.gov (United States)

    Sato, Naoki

    2010-07-01

    PsbP is a thylakoid lumen protein involved in oxygen evolution in photosystem II (PSII) in green plants. Genomic analysis identified a number of PsbP homologs in plants, algae, and cyanobacteria. To analyze the transition of cyanobacterial PsbO/U/V complex to PsbO/P/Q complex in green plants, the evolutionary history of the PsbP superfamily was reconstructed. Phylogenetic analyses suggested that PsbP homologs be classified into eight major families (A-H), which were also characterized by specific insertion/deletion of short segments, as found by sequence alignment and homology modeling. Family A represented authentic PsbP proteins involved in oxygen evolution. The cyanobacterial PsbP and plant/algal PPL (Family H), having the simplest structure, should be considered as the root of all other families of PsbP, which subsequently gained various short, family-specific structural motifs during diversification of PsbP families. Interestingly, segments specific to Family A proteins were found arranged as a ring surrounding the modeled Arabidopsis PsbP protein. These results suggest that Family A-specific additions of short segments played a decisive role in the transition of PsbO/U/V to PsbO/P/Q complex in green plants. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Structural model analysis of multiple quantitative traits.

    Directory of Open Access Journals (Sweden)

    Renhua Li

    2006-07-01

    Full Text Available We introduce a method for the analysis of multilocus, multitrait genetic data that provides an intuitive and precise characterization of genetic architecture. We show that it is possible to infer the magnitude and direction of causal relationships among multiple correlated phenotypes and illustrate the technique using body composition and bone density data from mouse intercross populations. Using these techniques we are able to distinguish genetic loci that affect adiposity from those that affect overall body size and thus reveal a shortcoming of standardized measures such as body mass index that are widely used in obesity research. The identification of causal networks sheds light on the nature of genetic heterogeneity and pleiotropy in complex genetic systems.

  4. Xenon and iodine reveal multiple distinct exotic xenon components in Efremovka "nanodiamonds"

    Science.gov (United States)

    Gilmour, J. D.; Holland, G.; Verchovsky, A. B.; Fisenko, A. V.; Crowther, S. A.; Turner, G.

    2016-03-01

    We identify new xenon components in a nanodiamond-rich residue from the reduced CV3 chondrite Efremovka. We demonstrate for the first time that these, and the previously identified xenon components Xe-P3 and Xe-P6, are associated with elevated I/Xe ratios. The 129I/127I ratio associated with xenon loss from these presolar compositions during processing on planetesimals in the early solar system was (0.369 ± 0.019) × 10-4, a factor of 3-4 lower than the canonical value. This suggests either incorporation of iodine into carbonaceous grains before the last input of freshly synthesized 129I to the solar system's precursor material, or loss of noble gases during processing of planetesimals around 30 Myr after solar system formation. The xenon/iodine ratios and model closure ages were revealed by laser step pyrolysis analysis of a neutron-irradiated, coarse-grained nanodiamond separate. Three distinct low temperature compositions are identified by characteristic I/Xe ratios and 136Xe/132Xe ratios. There is some evidence of multiple compositions with distinct I/Xe ratios in the higher temperature releases associated with Xe-P6. The presence of iodine alongside Q-Xe and these components in nanodiamonds constrains the pathway by which extreme volatiles entered the solid phase and may facilitate the identification of their carriers. There is no detectable iodine contribution to the presolar Xe-HL component, which is released at intermediate temperatures; this suggests a distinct trapping process. Releases associated with the other components all include significant contributions of 128Xe produced from iodine by neutron capture during reactor irradiation. We propose a revised model relating the origin of Xe-P3 (which exhibits an s-process deficit) through a ;Q-process; to the Q component (which makes the dominant contribution to the heavy noble gas budget of primitive material). The Q-process incorporates noble gases and iodine into specific carbonaceous phases with mass

  5. Asteroid Models from Multiple Data Sources

    CERN Document Server

    Durech, J; Delbo, M; Kaasalainen, M; Viikinkoski, M

    2015-01-01

    In the past decade, hundreds of asteroid shape models have been derived using the lightcurve inversion method. At the same time, a new framework of 3-D shape modeling based on the combined analysis of widely different data sources such as optical lightcurves, disk-resolved images, stellar occultation timings, mid-infrared thermal radiometry, optical interferometry, and radar delay-Doppler data, has been developed. This multi-data approach allows the determination of most of the physical and surface properties of asteroids in a single, coherent inversion, with spectacular results. We review the main results of asteroid lightcurve inversion and also recent advances in multi-data modeling. We show that models based on remote sensing data were confirmed by spacecraft encounters with asteroids, and we discuss how the multiplication of highly detailed 3-D models will help to refine our general knowledge of the asteroid population. The physical and surface properties of asteroids, i.e., their spin, 3-D shape, densit...

  6. Mixtures of multiplicative cascade models in geochemistry

    Directory of Open Access Journals (Sweden)

    F. P. Agterberg

    2007-05-01

    Full Text Available Multifractal modeling of geochemical map data can help to explain the nature of frequency distributions of element concentration values for small rock samples and their spatial covariance structure. Useful frequency distribution models are the lognormal and Pareto distributions which plot as straight lines on logarithmic probability and log-log paper, respectively. The model of de Wijs is a simple multiplicative cascade resulting in discrete logbinomial distribution that closely approximates the lognormal. In this model, smaller blocks resulting from dividing larger blocks into parts have concentration values with constant ratios that are scale-independent. The approach can be modified by adopting random variables for these ratios. Other modifications include a single cascade model with ratio parameters that depend on magnitude of concentration value. The Turcotte model, which is another variant of the model of de Wijs, results in a Pareto distribution. Often a single straight line on logarithmic probability or log-log paper does not provide a good fit to observed data and two or more distributions should be fitted. For example, geochemical background and anomalies (extremely high values have separate frequency distributions for concentration values and for local singularity coefficients. Mixtures of distributions can be simulated by adding the results of separate cascade models. Regardless of properties of background, an unbiased estimate can be obtained of the parameter of the Pareto distribution characterizing anomalies in the upper tail of the element concentration frequency distribution or lower tail of the local singularity distribution. Computer simulation experiments and practical examples are used to illustrate the approach.

  7. HUBBLE SPACE TELESCOPE REVEALS MULTIPLE SUB-GIANT BRANCH IN EIGHT GLOBULAR CLUSTERS

    Energy Technology Data Exchange (ETDEWEB)

    Piotto, G.; Nascimbeni, V. [Dipartimento di Astronomia, Universita di Padova, Vicolo dell' Osservatorio 3, I-35122 Padova (Italy); Milone, A. P.; Aparicio, A. [Instituto de Astrofisica de Canarias, E-38200 La Laguna, Tenerife, Canary Islands (Spain); Anderson, J.; Bellini, A. [Space Telescope Science Institute, 3800 San Martin Drive, Baltimore, MD 21218 (United States); Bedin, L. R. [INAF-Osservatorio Astronomico di Padova, Vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Cassisi, S. [INAF-Osservatorio Astronomico di Collurania, via Mentore Maggini, I-64100 Teramo (Italy); Marino, A. F., E-mail: giampaolo.piotto@unipd.it, E-mail: luigi.bedin@oapd.inaf.it, E-mail: milone@iac.es, E-mail: aparicio@iac.es, E-mail: jayander@stsci.edu, E-mail: bellini@stsci.edu, E-mail: cassisi@oa-teramo.inaf.it, E-mail: amarino@MPA-Garching.MPG.DE [Max Planck Institute for Astrophysics, Postfach 1317, D-85741 Garching (Germany)

    2012-11-20

    In the last few years many globular clusters (GCs) have revealed complex color-magnitude diagrams, with the presence of multiple main sequences (MSs), broad or multiple sub-giant branches (SGBs) and MS turnoffs, and broad or split red giant branches (RGBs). After a careful correction for differential reddening, high-accuracy photometry with the Hubble Space Telescope (HST) presented in this paper reveals a broadened or even split SGB in five additional Milky Way GCs: NGC 362, NGC 5286, NGC 6656, NGC 6715, and NGC 7089. In addition, we confirm (with new and archival HST data) the presence of a split SGB in 47 Tuc, NGC 1851, and NGC 6388. The fraction of faint SGB stars with respect to the entire SGB population varies from one cluster to another and ranges from {approx}0.03 for NGC 362 to {approx}0.50 for NGC 6715. The average magnitude difference between the bright SGB and the faint SGB is almost the same at different wavelengths. This peculiarity is consistent with the presence of two groups of stars with either an age difference of about 1-2 Gyr or a significant difference in their overall C+N+O content.

  8. The relationship between psoriasis and depression: A multiple mediation model.

    Science.gov (United States)

    Łakuta, Patryk; Marcinkiewicz, Kamil; Bergler-Czop, Beata; Brzezińska-Wcisło, Ligia

    2016-12-01

    This study examined the relationship between psoriasis and depression, proposing a multiple mediation model to analyse the relationship. A total of 193 patients with psoriasis aged 20-67 years completed the Beck Depression Inventory, the Stigmatization Scale, the Appearance Schemas Inventory-Revised, and the Body Emotions Scale. The Body Surface Area index was used to assess severity of psoriasis. Serial multiple mediation analysis revealed that experiences of stigmatization, maladaptive beliefs about appearance and its salience to one's self-evaluation, and negative emotional attitudes towards the body, jointly, sequentially mediated the relationship between the presence of skin lesions of psoriasis and depressive symptoms. These results highlight the importance of the associations between stigmatization and cognitive and affective aspects of body image in relation to depression in patients with psoriasis. We suggest that prevention and intervention programs for psoriasis patients that target body image enhancement would be worthy of further research.

  9. Airport choice model in multiple airport regions

    Directory of Open Access Journals (Sweden)

    Claudia Muñoz

    2017-02-01

    Full Text Available Purpose: This study aims to analyze travel choices made by air transportation users in multi airport regions because it is a crucial component when planning passenger redistribution policies. The purpose of this study is to find a utility function which makes it possible to know the variables that influence users’ choice of the airports on routes to the main cities in the Colombian territory. Design/methodology/approach: This research generates a Multinomial Logit Model (MNL, which is based on the theory of maximizing utility, and it is based on the data obtained on revealed and stated preference surveys applied to users who reside in the metropolitan area of Aburrá Valley (Colombia. This zone is the only one in the Colombian territory which has two neighboring airports for domestic flights. The airports included in the modeling process were Enrique Olaya Herrera (EOH Airport and José María Córdova (JMC Airport. Several structure models were tested, and the MNL proved to be the most significant revealing the common variables that affect passenger airport choice include the airfare, the price to travel the airport, and the time to get to the airport. Findings and Originality/value: The airport choice model which was calibrated corresponds to a valid powerful tool used to calculate the probability of each analyzed airport of being chosen for domestic flights in the Colombian territory. This is done bearing in mind specific characteristic of each of the attributes contained in the utility function. In addition, these probabilities will be used to calculate future market shares of the two airports considered in this study, and this will be done generating a support tool for airport and airline marketing policies.

  10. Dealing with Multiple Solutions in Structural Vector Autoregressive Models.

    Science.gov (United States)

    Beltz, Adriene M; Molenaar, Peter C M

    2016-01-01

    Structural vector autoregressive models (VARs) hold great potential for psychological science, particularly for time series data analysis. They capture the magnitude, direction of influence, and temporal (lagged and contemporaneous) nature of relations among variables. Unified structural equation modeling (uSEM) is an optimal structural VAR instantiation, according to large-scale simulation studies, and it is implemented within an SEM framework. However, little is known about the uniqueness of uSEM results. Thus, the goal of this study was to investigate whether multiple solutions result from uSEM analysis and, if so, to demonstrate ways to select an optimal solution. This was accomplished with two simulated data sets, an empirical data set concerning children's dyadic play, and modifications to the group iterative multiple model estimation (GIMME) program, which implements uSEMs with group- and individual-level relations in a data-driven manner. Results revealed multiple solutions when there were large contemporaneous relations among variables. Results also verified several ways to select the correct solution when the complete solution set was generated, such as the use of cross-validation, maximum standardized residuals, and information criteria. This work has immediate and direct implications for the analysis of time series data and for the inferences drawn from those data concerning human behavior.

  11. Multiple Temperature Model for Near Continuum Flows

    Energy Technology Data Exchange (ETDEWEB)

    XU, Kun; Liu, Hongwei [Hong Kong University of Science and Technology, Kowloon (Hong Kong); Jiang, Jianzheng [Chinese Academy ofSciences, Beijing (China)

    2007-09-15

    In the near continuum flow regime, the flow may have different translational temperatures in different directions. It is well known that for increasingly rarefied flow fields, the predictions from continuum formulation, such as the Navier-Stokes equations, lose accuracy. These inaccuracies may be partially due to the single temperature assumption in the Navier-Stokes equations. Here, based on the gas-kinetic Bhatnagar-Gross-Krook (BGK) equation, a multitranslational temperature model is proposed and used in the flow calculations. In order to fix all three translational temperatures, two constraints are additionally proposed to model the energy exchange in different directions. Based on the multiple temperature assumption, the Navier-Stokes relation between the stress and strain is replaced by the temperature relaxation term, and the Navier-Stokes assumption is recovered only in the limiting case when the flow is close to the equilibrium with the same temperature in different directions. In order to validate the current model, both the Couette and Poiseuille flows are studied in the transition flow regime.

  12. A model of interacting multiple choices of continuous opinions

    CERN Document Server

    Chou, C -I

    2016-01-01

    We present a model of interacting multiple choices of opinions. At each step of the process, a listener is persuaded by his/her neighbour, the lobbyist, to modify his/her opinion on two different choices of event. Whether or not the listener will be convinced by the lobbyist depends on the difference between his/her opinion with that of the lobbyist, and with that of the revealed social opinion (the social pressure). If the listener is convinced, he/she will modify his/her opinion and update his/her revealed preference, and proceed to persuade his/her next neighbour. If the listener is not convinced by the lobbyist, he/she will retain his/her revealed preference, and try to persuade the lobbyist to change his/her opinion. In this case, the direction of opinion propagation is reversed. A consensus is reached when all the revealed preference is the same. Our numerical results show that consensus can always be attained in this model. However, the time needed to achieve consensus, or the so-called convergence tim...

  13. TIME SERIES FORECASTING WITH MULTIPLE CANDIDATE MODELS: SELECTING OR COMBINING?

    Institute of Scientific and Technical Information of China (English)

    YU Lean; WANG Shouyang; K. K. Lai; Y.Nakamori

    2005-01-01

    Various mathematical models have been commonly used in time series analysis and forecasting. In these processes, academic researchers and business practitioners often come up against two important problems. One is whether to select an appropriate modeling approach for prediction purposes or to combine these different individual approaches into a single forecast for the different/dissimilar modeling approaches. Another is whether to select the best candidate model for forecasting or to mix the various candidate models with different parameters into a new forecast for the same/similar modeling approaches. In this study, we propose a set of computational procedures to solve the above two issues via two judgmental criteria. Meanwhile, in view of the problems presented in the literature, a novel modeling technique is also proposed to overcome the drawbacks of existing combined forecasting methods. To verify the efficiency and reliability of the proposed procedure and modeling technique, the simulations and real data examples are conducted in this study.The results obtained reveal that the proposed procedure and modeling technique can be used as a feasible solution for time series forecasting with multiple candidate models.

  14. Multiple Retrieval Models and Regression Models for Prior Art Search

    CERN Document Server

    Lopez, Patrice

    2009-01-01

    This paper presents the system called PATATRAS (PATent and Article Tracking, Retrieval and AnalysiS) realized for the IP track of CLEF 2009. Our approach presents three main characteristics: 1. The usage of multiple retrieval models (KL, Okapi) and term index definitions (lemma, phrase, concept) for the three languages considered in the present track (English, French, German) producing ten different sets of ranked results. 2. The merging of the different results based on multiple regression models using an additional validation set created from the patent collection. 3. The exploitation of patent metadata and of the citation structures for creating restricted initial working sets of patents and for producing a final re-ranking regression model. As we exploit specific metadata of the patent documents and the citation relations only at the creation of initial working sets and during the final post ranking step, our architecture remains generic and easy to extend.

  15. In vivo models of multiple system atrophy.

    Science.gov (United States)

    Fernagut, Pierre-Olivier; Ghorayeb, Imad; Diguet, Elsa; Tison, François

    2005-08-01

    Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

  16. Modeling and characterization of multiple coupled lines

    Science.gov (United States)

    Tripathi, Alok

    1999-10-01

    A configuration-oriented circuit model for multiple coupled lines in an inhomogeneous medium is developed and presented in this thesis. This circuit model consists of a network of uncoupled transmission lines and is readily modeled with simulation tools like LIBRA© and SPICE ©. It provides an equivalent circuit representation which is simple and topologically meaningful as compared to the model based on modal decomposition. The configuration-oriented model is derived by decomposing the immittance matrices associated with an n coupled line 2n-port system. Time- and frequency- domain simulations of typical coupled line multiports are included to exemplify the utility of the model. The model is useful for the simulation and design of general single and multilayer coupled line components, such as filters and couplers, and for the investigation of signal integrity issues including crosstalk in interconnects associated with high speed digital and mixed signal electronic modules and packages. It is shown that multiconductor lossless structures in an inhomogeneous medium can be characterized by multiport time-domain reflection (MR) measurements. A synthesis technique of an equivalent lossless (non-dispersive) uniform multiconductor n coupled lines (UMCL) 2n-port system from the measured discrete time-domain reflection response is presented. This procedure is based on the decomposition of the characteristic immittance matrices of the UMCL in terms of partial mode immittance matrices. The decomposition scheme leads to the discrete transition matrix function of a UMCL 2n-port system. This in turn establishes a relationship between the normal-mode parameters of the UMCL and the measured impulse reflection and transmission response. Equivalence between the synthesis procedure presented in this thesis and the solution of a special form of an algebraic Riccati matrix equation whose solution can lead to the normal-mode parameters and a real termination network is illustrated. In

  17. Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Hongying; Takagi, Akira [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Kayano, Hidekazu [Department of Pathology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Koyama, Isamu [Department of Digestive and General Surgery, Saitama International Medical Center, Faculty of Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Morisseau, Christophe; Hammock, Bruce D. [Department of Entomology and Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616-8584 (United States); Akatsuka, Toshitaka, E-mail: akatsuka@saitama-med.ac.jp [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan)

    2012-04-01

    In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside both cell types, but the most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells. -- Highlights: ► We examine expression of five mEH epitopes in human cells. ► Remarkable differences exist between hepatocytes and PBMC. ► mEH expression in cell lines differs depending on several factors. ► Some glioblastoma cell lines reveal marked surface expression of mEH. ► Topology of mEH on the cell

  18. Mathematical Modeling of Loop Heat Pipes with Multiple Capillary Pumps and Multiple Condensers. Part 1; Stead State Stimulations

    Science.gov (United States)

    Hoang, Triem T.; OConnell, Tamara; Ku, Jentung

    2004-01-01

    Loop Heat Pipes (LHPs) have proven themselves as reliable and robust heat transport devices for spacecraft thermal control systems. So far, the LHPs in earth-orbit satellites perform very well as expected. Conventional LHPs usually consist of a single capillary pump for heat acquisition and a single condenser for heat rejection. Multiple pump/multiple condenser LHPs have shown to function very well in ground testing. Nevertheless, the test results of a dual pump/condenser LHP also revealed that the dual LHP behaved in a complicated manner due to the interaction between the pumps and condensers. Thus it is redundant to say that more research is needed before they are ready for 0-g deployment. One research area that perhaps compels immediate attention is the analytical modeling of LHPs, particularly the transient phenomena. Modeling a single pump/single condenser LHP is difficult enough. Only a handful of computer codes are available for both steady state and transient simulations of conventional LHPs. No previous effort was made to develop an analytical model (or even a complete theory) to predict the operational behavior of the multiple pump/multiple condenser LHP systems. The current research project offered a basic theory of the multiple pump/multiple condenser LHP operation. From it, a computer code was developed to predict the LHP saturation temperature in accordance with the system operating and environmental conditions.

  19. Identification of Demand Models of Multiple Purchases

    OpenAIRE

    Itai Sher; Kyoo il Kim

    2012-01-01

    We study the nonparametric identification of distributions of utility functions in a multiple purchase setting with a finite number of consumers. Each utility function takes as arguments subsets or, alternatively, quantities of the multiple goods. We exploit mathematical insights from auction theory to generically identify the distribution of utility functions. We use price variation and aggregate data on the sales of each product, but not on individual level purchases or the total sales of b...

  20. Multiple bases of human intelligence revealed by cortical thickness and neural activation.

    Science.gov (United States)

    Choi, Yu Yong; Shamosh, Noah A; Cho, Sun Hee; DeYoung, Colin G; Lee, Min Joo; Lee, Jong-Min; Kim, Sun I; Cho, Zang-Hee; Kim, Kyungjin; Gray, Jeremy R; Lee, Kun Ho

    2008-10-08

    We hypothesized that individual differences in intelligence (Spearman's g) are supported by multiple brain regions, and in particular that fluid (gF) and crystallized (gC) components of intelligence are related to brain function and structure with a distinct profile of association across brain regions. In 225 healthy young adults scanned with structural and functional magnetic resonance imaging sequences, regions of interest (ROIs) were defined on the basis of a correlation between g and either brain structure or brain function. In these ROIs, gC was more strongly related to structure (cortical thickness) than function, whereas gF was more strongly related to function (blood oxygenation level-dependent signal during reasoning) than structure. We further validated this finding by generating a neurometric prediction model of intelligence quotient (IQ) that explained 50% of variance in IQ in an independent sample. The data compel a nuanced view of the neurobiology of intelligence, providing the most persuasive evidence to date for theories emphasizing multiple distributed brain regions differing in function.

  1. The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways.

    Science.gov (United States)

    Lim, Megan S; Carlson, Mary L; Crockett, David K; Fillmore, G Chris; Abbott, David R; Elenitoba-Johnson, Olaotan F; Tripp, Sheryl R; Rassidakis, George Z; Medeiros, L Jeffrey; Szankasi, Philippe; Elenitoba-Johnson, Kojo S J

    2009-08-20

    Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is a key oncogenic event in the pathogenesis of most anaplastic large cell lymphomas (ALCLs). The proteomic network alterations produced by this aberration remain largely uncharacterized. Using a mass spectrometry (MS)-driven approach to identify changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ribosome synthesis, survival, apoptosis evasion, angiogenesis, and cytoarchitectural organization. MS-based findings were confirmed using Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas. A subset of the proteins distinguished NPM/ALK-positive ALCLs from NPM/ALK-negative ALCLs and Hodgkin lymphoma. The multiple NPM/ALK-deregulated pathways identified by MS analysis also predicted novel biologic effects of NPM/ALK expression. In this regard, we showed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44ERK, and FRAP/mTOR signaling pathways. These findings reveal that the NPM/ALK alteration affects diverse cellular pathways, and provide novel insights into NPM/ALK-positive ALCL pathobiology. Our studies carry important implications for the use of MS-driven approaches for the elucidation of neoplastic pathobiology, the identification of novel diagnostic biomarkers, and pathogenetically relevant therapeutic targets.

  2. Novel centrosomal protein reveals the presence of multiple centrosomes in turkey (Meleagris gallopavo) bnbn binucleated erythrocytes.

    Science.gov (United States)

    Woods, C M; Zhu, J; Coleman, T; Bloom, S E; Lazarides, E

    1995-02-01

    The phenotype of the bnbn hemolytic anemia mutation in the domestic turkey is manifested as binucleation specifically in the definitive erythrocyte lineage, most likely as the consequence of anomolous centrosomal activity (Bloom et al., 1970; Searle and Bloom, 1979). Here we have identified in turkey two variants of the novel, centrosomally-associated erythroid-specific protein p23. One variant is Ca(2+)-sensitive and is highly homologous to its chick counterpart (Zhu et al., 1995, accompanying paper). The other, p21 is a truncated form resulting from a 62 amino acid deletion from the 3' end and a 40 amino acid insertion at the 5' end, and appears to lack Ca(2+)-sensitivity. These proteins are localized at the marginal band, centrosomes and nuclear membrane of differentiated erythrocytes. Anti-p23/p21 immunofluorescence revealed the presence of multiple centrosomes in bnbn erythrocytes. We therefore undertook a detailed genetic analysis to determine whether the p21 variant represented the bn mutation. Initial tests of normal BnBn and mutant bnbn individuals suggested that the p23/p21 proteins might be encoded by the Bn/bn genes. However, further genetic tests demonstrated independent segregation for these two genetic loci. Thus, these proteins are encoded by the heretofore undescribed genes, p23/p21, mapping to an autosomal locus in the turkey genome.

  3. Phylogeny of a genomically diverse group of elymus (poaceae allopolyploids reveals multiple levels of reticulation.

    Directory of Open Access Journals (Sweden)

    Roberta J Mason-Gamer

    Full Text Available The grass tribe Triticeae (=Hordeeae comprises only about 300 species, but it is well known for the economically important crop plants wheat, barley, and rye. The group is also recognized as a fascinating example of evolutionary complexity, with a history shaped by numerous events of auto- and allopolyploidy and apparent introgression involving diploids and polyploids. The genus Elymus comprises a heterogeneous collection of allopolyploid genome combinations, all of which include at least one set of homoeologs, designated St, derived from Pseudoroegneria. The current analysis includes a geographically and genomically diverse collection of 21 tetraploid Elymus species, and a single hexaploid species. Diploid and polyploid relationships were estimated using four molecular data sets, including one that combines two regions of the chloroplast genome, and three from unlinked nuclear genes: phosphoenolpyruvate carboxylase, β-amylase, and granule-bound starch synthase I. Four gene trees were generated using maximum likelihood, and the phylogenetic placement of the polyploid sequences reveals extensive reticulation beyond allopolyploidy alone. The trees were interpreted with reference to numerous phenomena known to complicate allopolyploid phylogenies, and introgression was identified as a major factor in their history. The work illustrates the interpretation of complicated phylogenetic results through the sequential consideration of numerous possible explanations, and the results highlight the value of careful inspection of multiple independent molecular phylogenetic estimates, with particular focus on the differences among them.

  4. Phylogeny of a genomically diverse group of elymus (poaceae) allopolyploids reveals multiple levels of reticulation.

    Science.gov (United States)

    Mason-Gamer, Roberta J

    2013-01-01

    The grass tribe Triticeae (=Hordeeae) comprises only about 300 species, but it is well known for the economically important crop plants wheat, barley, and rye. The group is also recognized as a fascinating example of evolutionary complexity, with a history shaped by numerous events of auto- and allopolyploidy and apparent introgression involving diploids and polyploids. The genus Elymus comprises a heterogeneous collection of allopolyploid genome combinations, all of which include at least one set of homoeologs, designated St, derived from Pseudoroegneria. The current analysis includes a geographically and genomically diverse collection of 21 tetraploid Elymus species, and a single hexaploid species. Diploid and polyploid relationships were estimated using four molecular data sets, including one that combines two regions of the chloroplast genome, and three from unlinked nuclear genes: phosphoenolpyruvate carboxylase, β-amylase, and granule-bound starch synthase I. Four gene trees were generated using maximum likelihood, and the phylogenetic placement of the polyploid sequences reveals extensive reticulation beyond allopolyploidy alone. The trees were interpreted with reference to numerous phenomena known to complicate allopolyploid phylogenies, and introgression was identified as a major factor in their history. The work illustrates the interpretation of complicated phylogenetic results through the sequential consideration of numerous possible explanations, and the results highlight the value of careful inspection of multiple independent molecular phylogenetic estimates, with particular focus on the differences among them.

  5. Explaining clinical behaviors using multiple theoretical models.

    Science.gov (United States)

    Eccles, Martin P; Grimshaw, Jeremy M; MacLennan, Graeme; Bonetti, Debbie; Glidewell, Liz; Pitts, Nigel B; Steen, Nick; Thomas, Ruth; Walker, Anne; Johnston, Marie

    2012-10-17

    , the mean construct scores were above the mid-point on the scale with median values across the five behaviors generally being above four out of seven and the range being from 1.53 to 6.01. Across all of the theories, the highest proportion of the variance explained was always for intention and the lowest was for behavior. The Knowledge-Attitudes-Behavior Model performed poorly across all behaviors and dependent variables; CSSRM also performed poorly. For TPB, SCT, II, and LT across the five behaviors, we predicted median R2 of 25% to 42.6% for intention, 6.2% to 16% for behavioral simulation, and 2.4% to 6.3% for behavior. We operationalized multiple theories measuring across five behaviors. Continuing challenges that emerge from our work are: better specification of behaviors, better operationalization of theories; how best to appropriately extend the range of theories; further assessment of the value of theories in different settings and groups; exploring the implications of these methods for the management of chronic diseases; and moving to experimental designs to allow an understanding of behavior change.

  6. Explaining clinical behaviors using multiple theoretical models

    Directory of Open Access Journals (Sweden)

    Eccles Martin P

    2012-10-01

    the five surveys. For the predictor variables, the mean construct scores were above the mid-point on the scale with median values across the five behaviors generally being above four out of seven and the range being from 1.53 to 6.01. Across all of the theories, the highest proportion of the variance explained was always for intention and the lowest was for behavior. The Knowledge-Attitudes-Behavior Model performed poorly across all behaviors and dependent variables; CSSRM also performed poorly. For TPB, SCT, II, and LT across the five behaviors, we predicted median R2 of 25% to 42.6% for intention, 6.2% to 16% for behavioral simulation, and 2.4% to 6.3% for behavior. Conclusions We operationalized multiple theories measuring across five behaviors. Continuing challenges that emerge from our work are: better specification of behaviors, better operationalization of theories; how best to appropriately extend the range of theories; further assessment of the value of theories in different settings and groups; exploring the implications of these methods for the management of chronic diseases; and moving to experimental designs to allow an understanding of behavior change.

  7. Multiple Lac-mediated loops revealed by Bayesian statistics and tethered particle motion

    CERN Document Server

    Johnson, Stephanie; Phillips, Rob; Wiggins, Chris H; Lindén, Martin

    2014-01-01

    The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcriptional regulation, the number and conformations of loop structures accessible to LacI remain unclear, though the importance of multiple co-existing loops has been implicated in interactions between LacI and other cellular regulators of gene expression. To probe this issue, we have developed a new analysis method for tethered particle motion (TPM), a versatile and commonly-used in vitro single-molecule technique. Our method, vbTPM, is based on a variational Bayes treatment of hidden Markov models. It learns the number of distinct states (i.e., DNA-protein conformations) directly from TPM data with better resolution than existing methods, while easily correcting for common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated loops, we are able to resolve three distinct loop structures, more than previously reported at ...

  8. Affine LIBOR Models with Multiple Curves

    DEFF Research Database (Denmark)

    Grbac, Zorana; Papapantoleon, Antonis; Schoenmakers, John

    2015-01-01

    We introduce a multiple curve framework that combines tractable dynamics and semianalytic pricing formulas with positive interest rates and basis spreads. Negative rates and positive spreads can also be accommodated in this framework. The dynamics of overnight indexed swap and LIBOR rates...... with dependent LIBOR rates is developed that allows for an efficient and accurate calibration to a system of caplet prices....

  9. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    Science.gov (United States)

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  10. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  11. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  12. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Science.gov (United States)

    Benitez, Cecil M; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H Efsun; Zhang, Jiajing; Dekker, Joseph D; Tucker, Haley O; Chang, Howard Y; Kim, Seung K

    2014-10-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  13. A Unified Mutual Coupling Model for Multiple Antenna Systems

    Institute of Scientific and Technical Information of China (English)

    WU Yu-jiang; NIE Zai-ping

    2006-01-01

    A unified mutual coupling model for multiple antenna communication systems based on moment methods is proposed. This model combines antenna coupling and RF front-end circuit coupling, thus providing a more accurate and complete analysis of the mutual coupling effect on multiple antenna systems.

  14. Analysis and application of opinion model with multiple topic interactions

    Science.gov (United States)

    Xiong, Fei; Liu, Yun; Wang, Liang; Wang, Ximeng

    2017-08-01

    To reveal heterogeneous behaviors of opinion evolution in different scenarios, we propose an opinion model with topic interactions. Individual opinions and topic features are represented by a multidimensional vector. We measure an agent's action towards a specific topic by the product of opinion and topic feature. When pairs of agents interact for a topic, their actions are introduced to opinion updates with bounded confidence. Simulation results show that a transition from a disordered state to a consensus state occurs at a critical point of the tolerance threshold, which depends on the opinion dimension. The critical point increases as the dimension of opinions increases. Multiple topics promote opinion interactions and lead to the formation of macroscopic opinion clusters. In addition, more topics accelerate the evolutionary process and weaken the effect of network topology. We use two sets of large-scale real data to evaluate the model, and the results prove its effectiveness in characterizing a real evolutionary process. Our model achieves high performance in individual action prediction and even outperforms state-of-the-art methods. Meanwhile, our model has much smaller computational complexity. This paper provides a demonstration for possible practical applications of theoretical opinion dynamics.

  15. State-shared model for multiple-input multiple-output systems

    Institute of Scientific and Technical Information of China (English)

    Zhenhua TIAN; Karlene A. HOO

    2005-01-01

    This work proposes a method to construct a state-shared model for multiple-input multiple-output (MIMO)systems. A state-shared model is defined as a linear time invariant state-space structure that is driven by measurement signals-the plant outputs and the manipulated variables, but shared by different multiple input/output models. The genesis of the state-shared model is based on a particular reduced non-minimal realization. Any such realization necessarily fulfills the requirement that the output of the state-shared model is an asymptotically correct estimate of the output of the plant, if the process model is selected appropriately. The approach is demonstrated on a nonlinear MIMO system- a physiological model of calcium fluxes that controls muscle contraction and relaxation in human cardiac myocytes.

  16. Modeling Multiple Risks: Hidden Domain of Attraction

    CERN Document Server

    Mitra, Abhimanyu

    2011-01-01

    Hidden regular variation is a sub-model of multivariate regular variation and facilitates accurate estimation of joint tail probabilities. We generalize the model of hidden regular variation to what we call hidden domain of attraction. We exhibit examples that illustrate the need for a more general model and discuss detection and estimation techniques.

  17. Multiple-membership multiple-classification models for social network and group dependences

    OpenAIRE

    Tranmer, Mark; Steel, David; Browne, William J

    2014-01-01

    The social network literature on network dependences has largely ignored other sources of dependence, such as the school that a student attends, or the area in which an individual lives. The multilevel modelling literature on school and area dependences has, in turn, largely ignored social networks. To bridge this divide, a multiple-membership multiple-classification modelling approach for jointly investigating social network and group dependences is presented. This allows social network and ...

  18. Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points.

    Science.gov (United States)

    Vainieri, Maria L; Blagborough, Andrew M; MacLean, Adam L; Haltalli, Myriam L R; Ruivo, Nicola; Fletcher, Helen A; Stumpf, Michael P H; Sinden, Robert E; Celso, Cristina Lo

    2016-06-01

    Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1(+) progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host.

  19. A Dirty Model for Multiple Sparse Regression

    CERN Document Server

    Jalali, Ali; Sanghavi, Sujay

    2011-01-01

    Sparse linear regression -- finding an unknown vector from linear measurements -- is now known to be possible with fewer samples than variables, via methods like the LASSO. We consider the multiple sparse linear regression problem, where several related vectors -- with partially shared support sets -- have to be recovered. A natural question in this setting is whether one can use the sharing to further decrease the overall number of samples required. A line of recent research has studied the use of \\ell_1/\\ell_q norm block-regularizations with q>1 for such problems; however these could actually perform worse in sample complexity -- vis a vis solving each problem separately ignoring sharing -- depending on the level of sharing. We present a new method for multiple sparse linear regression that can leverage support and parameter overlap when it exists, but not pay a penalty when it does not. A very simple idea: we decompose the parameters into two components and regularize these differently. We show both theore...

  20. Hair length, facial attractiveness, personality attribution: A multiple fitness model of hairdressing

    OpenAIRE

    Bereczkei, Tamas; Mesko, Norbert

    2007-01-01

    Multiple Fitness Model states that attractiveness varies across multiple dimensions, with each feature representing a different aspect of mate value. In the present study, male raters judged the attractiveness of young females with neotenous and mature facial features, with various hair lengths. Results revealed that the physical appearance of long-haired women was rated high, regardless of their facial attractiveness being valued high or low. Women rated as most attractive were those whose f...

  1. Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization

    CSIR Research Space (South Africa)

    Gcebe, N

    2017-04-01

    Full Text Available Journal of Systematic and Evolutionary Microbiology: DOI 10.1099/ijsem.0.001678 Mycobacterium malmesburyense sp. nov., a non-tuberculous species of the genus Mycobacterium revealed by multiple gene sequence characterization Gcebe N Rutten V Gey...

  2. SDG and qualitative trend based model multiple scale validation

    Science.gov (United States)

    Gao, Dong; Xu, Xin; Yin, Jianjin; Zhang, Hongyu; Zhang, Beike

    2017-09-01

    Verification, Validation and Accreditation (VV&A) is key technology of simulation and modelling. For the traditional model validation methods, the completeness is weak; it is carried out in one scale; it depends on human experience. The SDG (Signed Directed Graph) and qualitative trend based multiple scale validation is proposed. First the SDG model is built and qualitative trends are added to the model. And then complete testing scenarios are produced by positive inference. The multiple scale validation is carried out by comparing the testing scenarios with outputs of simulation model in different scales. Finally, the effectiveness is proved by carrying out validation for a reactor model.

  3. Multiple View Stereo by Reflectance Modeling

    DEFF Research Database (Denmark)

    Kim, Sujung; Kim, Seong Dae; Dahl, Anders Lindbjerg

    2012-01-01

    we argue that a visual metric based on a surface reflectance model should be founded on more observations than the degrees of freedom (dof) of the reflectance model. If (partly) specular surfaces are to be handled, this implies a model with at least two dof. In this paper, we propose to construct...... visual metrics of more than one dof using the DAISY methodology, which compares favorably to the state of the art in the experiments carried out. These experiments are based on a novel data set of eight scenes with diffuse and specular surfaces and accompanying ground truth. The performance of six...

  4. A single predator multiple prey model with prey mutation

    Science.gov (United States)

    Mullan, Rory; Abernethy, Gavin M.; Glass, David H.; McCartney, Mark

    2016-11-01

    A multiple species predator-prey model is expanded with the introduction of a coupled map lattice for the prey, allowing the prey to mutate discretely into other prey species. The model is examined in its single predator, multiple mutating prey form. Two unimodal maps are used for the underlying dynamics of the prey species, with different predation strategies being used. Conclusions are drawn on how varying the control parameters of the model governs the overall behaviour and survival of the species. It is observed that in such a complex system, with multiple mutating prey, a large range of non-linear dynamics is possible.

  5. Statistical selection of multiple-input multiple-output nonlinear dynamic models of spike train transformation.

    Science.gov (United States)

    Song, Dong; Chan, Rosa H M; Marmarelis, Vasilis Z; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

    2007-01-01

    Multiple-input multiple-output nonlinear dynamic model of spike train to spike train transformations was previously formulated for hippocampal-cortical prostheses. This paper further described the statistical methods of selecting significant inputs (self-terms) and interactions between inputs (cross-terms) of this Volterra kernel-based model. In our approach, model structure was determined by progressively adding self-terms and cross-terms using a forward stepwise model selection technique. Model coefficients were then pruned based on Wald test. Results showed that the reduced kernel models, which contained much fewer coefficients than the full Volterra kernel model, gave good fits to the novel data. These models could be used to analyze the functional interactions between neurons during behavior.

  6. Infinite multiple membership relational modeling for complex networks

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel Nørgaard; Hansen, Lars Kai

    2011-01-01

    Learning latent structure in complex networks has become an important problem fueled by many types of networked data originating from practically all fields of science. In this paper, we propose a new non-parametric Bayesian multiple-membership latent feature model for networks. Contrary to exist......Learning latent structure in complex networks has become an important problem fueled by many types of networked data originating from practically all fields of science. In this paper, we propose a new non-parametric Bayesian multiple-membership latent feature model for networks. Contrary...... to existing multiplemembership models that scale quadratically in the number of vertices the proposed model scales linearly in the number of links admitting multiple-membership analysis in large scale networks. We demonstrate a connection between the single membership relational model and multiple membership...

  7. ID Model Construction and Validation: A Multiple Intelligences Case

    Science.gov (United States)

    Tracey, Monica W.; Richey, Rita C.

    2007-01-01

    This is a report of a developmental research study that aimed to construct and validate an instructional design (ID) model that incorporates the theory and practice of multiple intelligences (MI). The study consisted of three phases. In phase one, the theoretical foundations of multiple Intelligences and ID were examined to guide the development…

  8. Multiple Social Networks, Data Models and Measures for

    DEFF Research Database (Denmark)

    Magnani, Matteo; Rossi, Luca

    2017-01-01

    Multiple Social Network Analysis is a discipline defining models, measures, methodologies, and algorithms to study multiple social networks together as a single social system. It is particularly valuable when the networks are interconnected, e.g., the same actors are present in more than one...... network....

  9. Enhanced understanding of the terrestrial carbon cycle through multiple constraints in model-data-integration approaches

    Science.gov (United States)

    Carvalhais, N.; Forkel, M.; Oijen, M. V.; Keenan, T. F.; MacBean, N.; Rolinski, S.; Peylin, P. P.; Schuermann, G. J.; Zaehle, S.; Reichstein, M.

    2015-12-01

    The representation of exchanges of carbon, water and energy between the land surface and the atmosphere still reveals significant model limitations in explaining temporal and spatial variability. Despite agreement between models for contemporaneous periods, prognostic simulations reveal a strong between-model divergence regarding the role of the land surface in the global carbon cycle. The integration of multiple data-streams in inverse modelling approaches for parameterization and model evaluation, ultimately leads to model improvement. Here we explore multiple-constraint approaches ranging from in situ to regional and global spatial scales. Constraints include stocks and fluxes of water and carbon. We show that integrating multiple datasets contributes to a better representation of ecosystem dynamics in different models, from forest and dynamic vegetation models to land surface schemes. At site scale, model-data comparisons reveal substantial differences in the modelled temporal dynamics of carbon stocks and turnover times and their relationships with climate, especially at annual scales. Inter-annual variability remains a problem for all models, even after parameter optimization. At regional and global scales, the integration of multiple data-streams to constrain albedo, phenology and primary productivity patterns yields a significant improvement in regional simulations of vegetation dynamics, from seasons to longer-term trends. The role of environmental controls and vegetation dynamics in explaining recent trends in the amplitude of the seasonal cycle of atmospheric CO2 is evaluated using an improved dynamic vegetation model. We conclude by identifying major challenges in model-data-integration: to explore the information content in longer time series; avoid confounding effects of missing processes on parameter estimation; set up cost functions for multivariate-data integration; quantification of uncertainties arising from data bias, model structure, and

  10. Modelling of rate effects at multiple scales

    DEFF Research Database (Denmark)

    Pedersen, R.R.; Simone, A.; Sluys, L. J.

    2008-01-01

    At the macro- and meso-scales a rate dependent constitutive model is used in which visco-elasticity is coupled to visco-plasticity and damage. A viscous length scale effect is introduced to control the size of the fracture process zone. By comparison of the widths of the fracture process zone......, the length scale in the meso-model and the macro-model can be coupled. In this fashion, a bridging of length scales can be established. A computational analysis of  a Split Hopkinson bar test at medium and high impact load is carried out at macro-scale and meso-scale including information from  the micro-scale....

  11. Control design approaches for nonlinear systems using multiple models

    Institute of Scientific and Technical Information of China (English)

    Junyong ZHAI; Shumin FEI; Feipeng DA

    2007-01-01

    It is difficult to realize control for some complex nonlinear systems operated in different operating regions.Based on developing local models for different operating regions of the process, a novel algorithm using multiple models is proposed. It utilizes dynamic model bank to establish multiple local models, and their membership functions are defined according to respective regions. Then the nonlinear system is approximated to a weighted combination of the local models.The stability of the nonlinear system is proven. Finally, simulations are given to demonstrate the validity of the proposed method.

  12. Animal model of human disease. Multiple myeloma

    NARCIS (Netherlands)

    Radl, J.; Croese, J.W.; Zurcher, C.; Enden-Vieveen, M.H.M. van den; Leeuw, A.M. de

    1988-01-01

    Animal models of spontaneous and induced plasmacytomas in some inbred strains of mice have proven to be useful tools for different studies on tumorigenesis and immunoregulation. Their wide applicability and the fact that after their intravenous transplantation, the recipient mice developed bone

  13. Mathematical modeling on bacterial resistance to multiple antibiotics caused by spontaneous mutations.

    Science.gov (United States)

    Ibargüen-Mondragón, Eduardo; Mosquera, Saulo; Cerón, Miller; Burbano-Rosero, Edith Mariela; Hidalgo-Bonilla, Sandra P; Esteva, Lourdes; Romero-Leitón, Jhoana P

    2014-03-01

    We formulate a mathematical model that describes the population dynamics of bacteria exposed to multiple antibiotics simultaneously, assuming that acquisition of resistance is through mutations due to antibiotic exposure. Qualitative analysis reveals the existence of a free-bacteria equilibrium, resistant-bacteria equilibrium and an endemic equilibrium where both bacteria coexist.

  14. Study of Self-Organization Model of Multiple Mobile Robot

    OpenAIRE

    Li Shu-qin; Ceng Xian-yi; Xia De-shen

    2006-01-01

    A good organization model of multiple mobile robot should be able to improve the efficiency of the system, reduce the complication of robot interactions, and detract the difficulty of computation. From the sociology aspect of topology, structure and organization, this paper studies the multiple mobile robot organization formation and running mechanism in the dynamic, complicated and unknown environment. It presents and describes in detail a Hierarchical- Web Recursive Organization Model (HWRO...

  15. Teaching students to apply multiple physical modeling methods

    NARCIS (Netherlands)

    Wiegers, T.; Verlinden, J.C.; Vergeest, J.S.M.

    2014-01-01

    Design students should be able to explore a variety of shapes before elaborating one particular shape. Current modelling courses don’t address this issue. We developed the course Rapid Modelling, which teaches students to explore multiple shape models in a short time, applying different methods and

  16. A model for multiple scattering in GEANT4

    CERN Document Server

    Urbán, László

    2006-01-01

    We present a model to simulate the multiple scattering of charged particles in matter. The model is based on Lewis theory; it does not use the Moliere formalism. It simulates the scattering of a charged particle after a given step, computes the path length correction and the lateral displacement as well. This model is used in GEANT4.

  17. MULTIPLE IMPUTATION OF MISSING DATA IN SUSTAINABLE DEVELOPMENT MODELLING

    OpenAIRE

    Roberto Benedetti; Rita Lima; Alessandro Pandimiglio

    2006-01-01

    A multiple imputation technique is proposed to measure sustainable development using models of structural equations (LISREL) for the treatment of missing data. The reliability of such technique is verified comparing the estimation model with missing data to the estimation model with imputed data. The results show that the missing data problem significantly affect the estimation.

  18. Teaching students to apply multiple physical modeling methods

    NARCIS (Netherlands)

    Wiegers, T.; Verlinden, J.C.; Vergeest, J.S.M.

    2014-01-01

    Design students should be able to explore a variety of shapes before elaborating one particular shape. Current modelling courses don’t address this issue. We developed the course Rapid Modelling, which teaches students to explore multiple shape models in a short time, applying different methods and

  19. Insights revealed by rodent models of sugar binge eating.

    Science.gov (United States)

    Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

    2015-12-01

    Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

  20. Green communication: The enabler to multiple business models

    DEFF Research Database (Denmark)

    Lindgren, Peter; Clemmensen, Suberia; Taran, Yariv

    2010-01-01

    Companies stand at the forefront of a new business model reality with new potentials - that will change their basic understanding and practice of running their business models radically. One of the drivers to this change is green communication, its strong relation to green business models and its...... possibility to enable lower energy consumption. This paper shows how green communication enables innovation of green business models and multiple business models running simultaneously in different markets to different customers....

  1. A Methodological Self-Study of Quantitizing: Negotiating Meaning and Revealing Multiplicity

    Science.gov (United States)

    Seltzer-Kelly, Deborah; Westwood, Sean J.; Pena-Guzman, David M.

    2012-01-01

    This inquiry developed during the process of "quantitizing" qualitative data the authors had gathered for a mixed methods curriculum efficacy study. Rather than providing the intended rigor to their data coding process, their use of an intercoder reliability metric prompted their investigation of the multiplicity and messiness that, as they…

  2. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    Science.gov (United States)

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Random field model reveals structure of the protein recombinational landscape.

    Directory of Open Access Journals (Sweden)

    Philip A Romero

    Full Text Available We are interested in how intragenic recombination contributes to the evolution of proteins and how this mechanism complements and enhances the diversity generated by random mutation. Experiments have revealed that proteins are highly tolerant to recombination with homologous sequences (mutation by recombination is conservative; more surprisingly, they have also shown that homologous sequence fragments make largely additive contributions to biophysical properties such as stability. Here, we develop a random field model to describe the statistical features of the subset of protein space accessible by recombination, which we refer to as the recombinational landscape. This model shows quantitative agreement with experimental results compiled from eight libraries of proteins that were generated by recombining gene fragments from homologous proteins. The model reveals a recombinational landscape that is highly enriched in functional sequences, with properties dominated by a large-scale additive structure. It also quantifies the relative contributions of parent sequence identity, crossover locations, and protein fold to the tolerance of proteins to recombination. Intragenic recombination explores a unique subset of sequence space that promotes rapid molecular diversification and functional adaptation.

  4. Entrepreneurial intention modeling using hierarchical multiple regression

    Directory of Open Access Journals (Sweden)

    Marina Jeger

    2014-12-01

    Full Text Available The goal of this study is to identify the contribution of effectuation dimensions to the predictive power of the entrepreneurial intention model over and above that which can be accounted for by other predictors selected and confirmed in previous studies. As is often the case in social and behavioral studies, some variables are likely to be highly correlated with each other. Therefore, the relative amount of variance in the criterion variable explained by each of the predictors depends on several factors such as the order of variable entry and sample specifics. The results show the modest predictive power of two dimensions of effectuation prior to the introduction of the theory of planned behavior elements. The article highlights the main advantages of applying hierarchical regression in social sciences as well as in the specific context of entrepreneurial intention formation, and addresses some of the potential pitfalls that this type of analysis entails.

  5. Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior.

    Science.gov (United States)

    Nautiyal, Katherine M; Wall, Melanie M; Wang, Shuai; Magalong, Valerie M; Ahmari, Susanne E; Balsam, Peter D; Blanco, Carlos; Hen, René

    2017-01-18

    Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.Neuropsychopharmacology advance online publication, 18 January 2017; doi:10.1038/npp.2016.277.

  6. Boron isotopes reveal multiple metasomatic events in the mantle beneath the eastern North China Craton

    Science.gov (United States)

    Li, Hong-Yan; Zhou, Zhou; Ryan, Jeffrey G.; Wei, Gang-Jian; Xu, Yi-Gang

    2016-12-01

    Linkages inferred between the geochemical heterogeneity of the mantle beneath eastern Eurasia and the stagnant Pacific slab documented geophysically in its mantle transition zone are as yet not clearly characterized. In this paper we report new elemental and isotopic data for boron (B) on a suite of well-characterized Cenozoic basalts (alkali basalts, basanites and nephelinites), with ocean island basalt (OIB)-like trace element signatures from western Shandong of the eastern North China Craton (NCC). Correlations between major elements (e.g., FeOT versus SiO2), trace elements (e.g., CeN/PbN versus BaN/ThN) and radiogenic isotopes (e.g., 206Pb/204Pb versus 87Sr/86Sr) suggest these basalts are derived via the mixing of melts from two mantle components: a fluid mobile element (FME; such as Ba, K, Pb and Sr) enriched component, which is most evident in the alkali basalts, and a FME depleted mantle component that is more evident in the basanites and nephelinites. The alkali basalts in this study have lower B concentrations (1.4-2.2 μg/g) but higher δ11B (-4.9 to -1.4) values than the basanites and nephelinites (B = 2.1-5.0 μg/g; δ11B = -6.9 to -3.9), and all the samples have nearly constant B/Nb ratios between 0.03 and 0.07, similar to the observed range in B/Nb for intraplate lavas. Our high-SiO2 samples have higher δ11B than that of our low SiO2 samples, indicating that the B isotopic differences among our samples do not result from the addition of a continental crustal component in the mantle source, or direct crustal assimilation during the eruption process. The positive B versus Nb correlation suggests the B isotopic compositions of the western Shandong basalts primarily reflect the pre-eruptive compositions of their mantle sources. Correlations among B, Nd and Sr isotope signatures of the western Shandong basalts differ from those among basalts from plume settings (e.g., Azores and Hawaii), and are inconsistent with models suggesting single-step metasomatic

  7. Demand Model Combining Stated And Revealed Preference Data

    Directory of Open Access Journals (Sweden)

    Luciana Londero Brandli

    2007-10-01

    Full Text Available The revealed and stated preference methods have been contributing a lot for the development of the econometric literature in the attempt of determining the variables that influence the individual decision in a choice process. This article combines preference data, with the objective of obtaining the advantages of the complementarity of the forces and frankness of both types of data. The approach involves the estimate of a model only with RP data, only with SP data and combining RP and SP data. The application is in the housing market, where it is observed, through the literature, that most of the papers of the consumer's choice has restricted the only one approaches. The utility functions obtained show the relative importance of the attributes, the tendency of behavior through the signs and its significance statistical. The results analysis of the models indicates differences and similarities about the attribute’s behavior.

  8. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    Science.gov (United States)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  9. Molecular Code Division Multiple Access: Gaussian Mixture Modeling

    Science.gov (United States)

    Zamiri-Jafarian, Yeganeh

    Communications between nano-devices is an emerging research field in nanotechnology. Molecular Communication (MC), which is a bio-inspired paradigm, is a promising technique for communication in nano-network. In MC, molecules are administered to exchange information among nano-devices. Due to the nature of molecular signals, traditional communication methods can't be directly applied to the MC framework. The objective of this thesis is to present novel diffusion-based MC methods when multi nano-devices communicate with each other in the same environment. A new channel model and detection technique, along with a molecular-based access method, are proposed in here for communication between asynchronous users. In this work, the received molecular signal is modeled as a Gaussian mixture distribution when the MC system undergoes Brownian noise and inter-symbol interference (ISI). This novel approach demonstrates a suitable modeling for diffusion-based MC system. Using the proposed Gaussian mixture model, a simple receiver is designed by minimizing the error probability. To determine an optimum detection threshold, an iterative algorithm is derived which minimizes a linear approximation of the error probability function. Also, a memory-based receiver is proposed to improve the performance of the MC system by considering previously detected symbols in obtaining the threshold value. Numerical evaluations reveal that theoretical analysis of the bit error rate (BER) performance based on the Gaussian mixture model match simulation results very closely. Furthermore, in this thesis, molecular code division multiple access (MCDMA) is proposed to overcome the inter-user interference (IUI) caused by asynchronous users communicating in a shared propagation environment. Based on the selected molecular codes, a chip detection scheme with an adaptable threshold value is developed for the MCDMA system when the proposed Gaussian mixture model is considered. Results indicate that the

  10. An Ant-Based Model for Multiple Sequence Alignment

    CERN Document Server

    Guinand, Frédéric

    2008-01-01

    Multiple sequence alignment is a key process in today's biology, and finding a relevant alignment of several sequences is much more challenging than just optimizing some improbable evaluation functions. Our approach for addressing multiple sequence alignment focuses on the building of structures in a new graph model: the factor graph model. This model relies on block-based formulation of the original problem, formulation that seems to be one of the most suitable ways for capturing evolutionary aspects of alignment. The structures are implicitly built by a colony of ants laying down pheromones in the factor graphs, according to relations between blocks belonging to the different sequences.

  11. Evolving Four Part Harmony Using a Multiple Worlds Model

    DEFF Research Database (Denmark)

    Scirea, Marco; Brown, Joseph Alexander

    2015-01-01

    This application of the Multiple Worlds Model examines a collaborative fitness model for generating four part harmonies. In this model we have multiple populations and the fitness of the individuals is based on the ability of a member from each population to work with the members of other...... populations. We present the result of two experiments: the generation of compositions, given a static voice line, both in a constrained and unconstrained harmonic framework. The remaining three voices are evolved using this collaborative fitness function, which looks for a number of classical composition...

  12. Efficient Adoption and Assessment of Multiple Process Improvement Reference Models

    Directory of Open Access Journals (Sweden)

    Simona Jeners

    2013-06-01

    Full Text Available A variety of reference models such as CMMI, COBIT or ITIL support IT organizations to improve their processes. These process improvement reference models (IRMs cover different domains such as IT development, IT Services or IT Governance but also share some similarities. As there are organizations that address multiple domains and need to coordinate their processes in their improvement we present MoSaIC, an approach to support organizations to efficiently adopt and conform to multiple IRMs. Our solution realizes a semantic integration of IRMs based on common meta-models. The resulting IRM integration model enables organizations to efficiently implement and asses multiple IRMs and to benefit from synergy effects.

  13. A methodology to calibrate pedestrian walker models using multiple objectives

    NARCIS (Netherlands)

    Campanella, M.C.; Daamen, W.; Hoogendoorn, S.P.

    2012-01-01

    The application of walker models to simulate real situations require accuracy in several traffic situations. One strategy to obtain a generic model is to calibrate the parameters in several situations using multiple-objective functions in the optimization process. In this paper, we propose a general

  14. Immersed boundary lattice Boltzmann model based on multiple relaxation times.

    Science.gov (United States)

    Lu, Jianhua; Han, Haifeng; Shi, Baochang; Guo, Zhaoli

    2012-01-01

    As an alterative version of the lattice Boltzmann models, the multiple relaxation time (MRT) lattice Boltzmann model introduces much less numerical boundary slip than the single relaxation time (SRT) lattice Boltzmann model if some special relationship between the relaxation time parameters is chosen. On the other hand, most current versions of the immersed boundary lattice Boltzmann method, which was first introduced by Feng and improved by many other authors, suffer from numerical boundary slip as has been investigated by Le and Zhang. To reduce such a numerical boundary slip, an immerse boundary lattice Boltzmann model based on multiple relaxation times is proposed in this paper. A special formula is given between two relaxation time parameters in the model. A rigorous analysis and the numerical experiments carried out show that the numerical boundary slip reduces dramatically by using the present model compared to the single-relaxation-time-based model.

  15. Multiple QoS modeling and algorithm in computational grid

    Institute of Scientific and Technical Information of China (English)

    Li Chunlin; Feng Meilai; Li Layuan

    2007-01-01

    Multiple QoS modeling and algorithm in grid system is considered.Grid QoS requirements can be formulated as a utility function for each task as a weighted sum of its each dimensional QoS utility functions.Multiple QoS constraint resource scheduling optimization in computational grid is distributed to two subproblems: optimization of grid user and grid resource provider.Grid QoS scheduling can be achieved by solving sub problems via an iterative algorithm.

  16. Modeling considerations for using expression data from multiple species.

    Science.gov (United States)

    Siewert, Elizabeth; Kechris, Katerina J

    2013-10-15

    Although genome-wide expression data sets from multiple species are now more commonly generated, there have been few studies on how to best integrate this type of correlated data into models. Starting with a single-species, linear regression model that predicts transcription factor binding sites as a case study, we investigated how best to take into account the correlated expression data when extending this model to multiple species. Using a multivariate regression model, we accounted for the phylogenetic relationships among the species in two ways: (i) a repeated-measures model, where the error term is constrained; and (ii) a Bayesian hierarchical model, where the prior distributions of the regression coefficients are constrained. We show that both multiple-species models improve predictive performance over the single-species model. When compared with each other, the repeated-measures model outperformed the Bayesian model. We suggest a possible explanation for the better performance of the model with the constrained error term. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  18. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes.

    Science.gov (United States)

    Paraboschi, Elvezia Maria; Cardamone, Giulia; Rimoldi, Valeria; Gemmati, Donato; Spreafico, Marta; Duga, Stefano; Soldà, Giulia; Asselta, Rosanna

    2015-09-30

    Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  19. Multiple aspects of northern hemispheric wintertime cold extremes as revealed by Markov chain analysis

    Science.gov (United States)

    Kim, Hye-Sil; Choi, Yong-Sang; Kim, Joo-Hong; Kim, WonMoo

    2017-02-01

    High-impact cold extremes have continued to bring devastating socioeconomic losses in recent years. In order to explain the exposure to cold extremes more comprehensively, this study investigates multiple aspects of boreal winter cold extremes, i.e., frequency, persistence, and entropy (Markovian descriptors). Cold extremes are defined by the bottom 10th percentile of daily minimum temperatures during 1950-2014 over the northern hemisphere. The spatial and temporal distributions of Markovian descriptors during 65 years are examined. Climatological mean fields show the spatial coincidence of higher frequency, shorter persistence, and higher entropy of cold extremes, and vice versa. In regard to the temporal variations over six representative regions of North America, Europe, and Asia, all regions share a decreasing tendency of frequency with the increases in regional winter mean temperature. By contrast, persistence and entropy show their intrinsic decadal variability depending on regions irrespective of the regional temperature variability, which give different information from frequency. Therefore, the exposure to cold extremes would not simply decrease with regional warming. Rather these results indicate that the descriptors with multiple aspects of the extremes would be needed to embrace the topical features as well as the holistic nature of cold extremes.

  20. AgMIP Training in Multiple Crop Models and Tools

    Science.gov (United States)

    Boote, Kenneth J.; Porter, Cheryl H.; Hargreaves, John; Hoogenboom, Gerrit; Thornburn, Peter; Mutter, Carolyn

    2015-01-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) has the goal of using multiple crop models to evaluate climate impacts on agricultural production and food security in developed and developing countries. There are several major limitations that must be overcome to achieve this goal, including the need to train AgMIP regional research team (RRT) crop modelers to use models other than the ones they are currently familiar with, plus the need to harmonize and interconvert the disparate input file formats used for the various models. Two activities were followed to address these shortcomings among AgMIP RRTs to enable them to use multiple models to evaluate climate impacts on crop production and food security. We designed and conducted courses in which participants trained on two different sets of crop models, with emphasis on the model of least experience. In a second activity, the AgMIP IT group created templates for inputting data on soils, management, weather, and crops into AgMIP harmonized databases, and developed translation tools for converting the harmonized data into files that are ready for multiple crop model simulations. The strategies for creating and conducting the multi-model course and developing entry and translation tools are reviewed in this chapter.

  1. Genetic analysis reveals multiple parentage in captive reared eastern hellbender salamanders (Cryptobranchus alleganiensis).

    Science.gov (United States)

    Unger, Shem D; Williams, Rod N

    2015-11-01

    Information on the parentage of captive reared clutches is vital for conservation head-starting programs. Molecular methods, such as genotyping individuals with hyper-variable markers, can elucidate the genealogical contribution of captive-reared, reintroduced individuals to native populations. In this study, we used 12 polymorphic microsatellite loci to infer parentage of a clutch of 18 eastern hellbenders collected from a single nest from Buffalo Creek, West Virginia, subsequently reared in captivity, and used for translocations in Indiana. Collectively, these markers successfully detected the presence of multiple parentage for this species of conservation concern presently used in captive management programs in zoos across many states. This study highlights the need for genetic analysis of captive reared clutches used in translocations to minimize the loss of genetic diversity and potential for genetic swamping at release sites.

  2. Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.

    Science.gov (United States)

    Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

    2014-12-19

    Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution.

  3. Dissecting the Multiple Myeloma-bone microenvironment reveals new therapeutic opportunities

    Science.gov (United States)

    Shay, G; Hazlehurst, L; Lynch, CC

    2015-01-01

    Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease. PMID:26423531

  4. Microstructural abnormalities in the trigeminal nerves of patients with trigeminal neuralgia revealed by multiple diffusion metrics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Beijing Key laboratory of MRI and Brain Informatics, Beijing (China); Li, Jiping [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Duan, Yunyun; Zhang, Mo [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Li, Yongjie [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Yuqing, E-mail: yuqzhang@sohu.com [Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2013-05-15

    Objective: To investigate microstructural tissue changes of trigeminal nerve (TGN) in patients with unilateral trigeminal neuralgia (TN) by multiple diffusion metrics, and correlate the diffusion indexes with the clinical variables. Methods: 16 patients with TN and 6 healthy controls (HC) were recruited into our study. All participants were imaged with a 3.0 T system with three-dimension time-of-flight (TOF) magnetic resonance angiography and fluid attenuated inversion recovery (FLAIR) DTI-sequence. We placed regions of interest over the root entry zone of the TGN and measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). The mean values of FA, MD, AD and RD were compared between the affected and unaffected sides in the same patient, and to HC values. The correlation between the side-to-side diffusion metric difference and clinical variables (disease duration and visual analogy scale, VAS) was further explored. Results: Compared with the unaffected side and HC, the affected side showed significantly decreased FA and increased RD; however, no significant changes of AD were found. A trend toward significantly increased MD was identified on the affected side comparing with the unaffected side. We also found the significant correlation between the FA reduction and VAS of pain (r = −0.55, p = 0.03). Conclusion: DTI can quantitatively assess the microstructural abnormalities of the affected TGN in patients with TN. Our results suggest demyelination without significant axonal injury is the essential pathological basis of the affected TGN by multiple diffusion metrics. The correlation between FA reduction and VAS suggests FA as a potential objective MRI biomarker to correlate with clinical severity.

  5. Modeling microstructural evolution of multiple texture components during recrystallization

    DEFF Research Database (Denmark)

    Vandermeer, R.A.; Juul Jensen, D.

    1994-01-01

    using stereological point and lineal measurements of microstructural properties in combination with EBSP analysis for orientation determinations. The potential of the models to describe the observed recrystallization behavior of heavily cold-rolled commercial aluminum was demonstrated. A successful MPM......Models were formulated in an effort to characterize recrystallization in materials with multiple texture components. The models are based on a microstructural path methodology (MPM). Experimentally the microstructural evolution of conmmercial aluminum during recrystallization was characterized...

  6. Multiple comparisons in genetic association studies: a hierarchical modeling approach.

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2014-02-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).

  7. Manifold learning for object tracking with multiple nonlinear models.

    Science.gov (United States)

    Nascimento, Jacinto C; Silva, Jorge G; Marques, Jorge S; Lemos, Joao M

    2014-04-01

    This paper presents a novel manifold learning algorithm for high-dimensional data sets. The scope of the application focuses on the problem of motion tracking in video sequences. The framework presented is twofold. First, it is assumed that the samples are time ordered, providing valuable information that is not presented in the current methodologies. Second, the manifold topology comprises multiple charts, which contrasts to the most current methods that assume one single chart, being overly restrictive. The proposed algorithm, Gaussian process multiple local models (GP-MLM), can deal with arbitrary manifold topology by decomposing the manifold into multiple local models that are probabilistic combined using Gaussian process regression. In addition, the paper presents a multiple filter architecture where standard filtering techniques are integrated within the GP-MLM. The proposed approach exhibits comparable performance of state-of-the-art trackers, namely multiple model data association and deep belief networks, and compares favorably with Gaussian process latent variable models. Extensive experiments are presented using real video data, including a publicly available database of lip sequences and left ventricle ultrasound images, in which the GP-MLM achieves state of the art results.

  8. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

    Directory of Open Access Journals (Sweden)

    Lewei Duan

    2013-01-01

    Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

  9. The visual pulvinar in tree shrews I. Multiple subdivisions revealed through acetylcholinesterase and Cat-301 chemoarchitecture.

    Science.gov (United States)

    Lyon, David C; Jain, Neeraj; Kaas, Jon H

    2003-12-22

    Tree shrews are highly visual mammals closely related to primates. They have a large visual pulvinar complex, but its organization and relation to visual cortex is only partly known. We processed brain sections through the pulvinar with seven different procedures in an effort to reveal histologically distinct compartments. The results revealed three major subdivisions. A dorsal subdivision, Pd, stains darkly for acetylcholinesterase (AChE) and occupies the dorsoposterior one-third of the pulvinar complex. A ventral subdivision, Pv, stains darkly when processed with the Cat-301 antibody and occupies the ventroanterior fifth of the pulvinar complex along the brachium of the superior colliculus. Unexpectedly, part of Pv is ventral to the brachium. A large central subdivision, Pc, stains moderately dark for AChE and cytochrome oxidase (CO), and very light for Cat-301. Pc includes about half of the pulvinar complex, with parts on both sides of the brachium of the superior colliculus. These architectonic results demonstrate that the pulvinar complex of tree shrews is larger and has more subdivisions than previously described. The complex resembles the pulvinar of primates by having a portion ventral to the brachium and by having histochemically distinct nuclei; the number of nuclei is less than in primates, however.

  10. Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

    Directory of Open Access Journals (Sweden)

    Sosef Marc SM

    2008-12-01

    Full Text Available Abstract Background Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1 a single break-up followed by a long isolation or 2 multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties. Results Our results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years – Myr coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times. Conclusion Molecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance

  11. Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning.

    Science.gov (United States)

    Frank, Michael J; Moustafa, Ahmed A; Haughey, Heather M; Curran, Tim; Hutchison, Kent E

    2007-10-09

    What are the genetic and neural components that support adaptive learning from positive and negative outcomes? Here, we show with genetic analyses that three independent dopaminergic mechanisms contribute to reward and avoidance learning in humans. A polymorphism in the DARPP-32 gene, associated with striatal dopamine function, predicted relatively better probabilistic reward learning. Conversely, the C957T polymorphism of the DRD2 gene, associated with striatal D2 receptor function, predicted the degree to which participants learned to avoid choices that had been probabilistically associated with negative outcomes. The Val/Met polymorphism of the COMT gene, associated with prefrontal cortical dopamine function, predicted participants' ability to rapidly adapt behavior on a trial-to-trial basis. These findings support a neurocomputational dissociation between striatal and prefrontal dopaminergic mechanisms in reinforcement learning. Computational maximum likelihood analyses reveal independent gene effects on three reinforcement learning parameters that can explain the observed dissociations.

  12. Cutting Edge: Il-1 Receptor-Associated Kinase 4 Structures Reveal Novel Features And Multiple Conformations

    Energy Technology Data Exchange (ETDEWEB)

    Kuglstatter, A.; Villasenor, A.G.; Shaw, D.; Lee, S.W.; Tsing, S.; Niu, L.; Song, K.W.; Barnett, J.W.; Browner, M.F.

    2007-07-09

    L-1R-associated kinase (IRAK)4 plays a central role in innate and adaptive immunity, and is a crucial component in IL-1/TLR signaling. We have determined the crystal structures of the apo and ligand-bound forms of human IRAK4 kinase domain. These structures reveal several features that provide opportunities for the design of selective IRAK4 inhibitors. The N-terminal lobe of the IRAK4 kinase domain is structurally distinctive due to a loop insertion after an extended N-terminal helix. The gatekeeper residue is a tyrosine, a unique feature of the IRAK family. The IRAK4 structures also provide insights into the regulation of its activity. In the apo structure, two conformations coexist, differing in the relative orientation of the two kinase lobes and the position of helix C. In the presence of an ATP analog only one conformation is observed, indicating that this is the active conformation.

  13. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.

    Science.gov (United States)

    Umezu, K; Sugawara, N; Chen, C; Haber, J E; Kolodner, R D

    1998-03-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10(4) to 10(5) times increased sensitivity to these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO-induced double-strand break at MAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages.

  14. Multiple-stage ambiguity in motion perception reveals global computation of local motion directions.

    Science.gov (United States)

    Rider, Andrew T; Nishida, Shin'ya; Johnston, Alan

    2016-12-01

    The motion of a 1D image feature, such as a line, seen through a small aperture, or the small receptive field of a neural motion sensor, is underconstrained, and it is not possible to derive the true motion direction from a single local measurement. This is referred to as the aperture problem. How the visual system solves the aperture problem is a fundamental question in visual motion research. In the estimation of motion vectors through integration of ambiguous local motion measurements at different positions, conventional theories assume that the object motion is a rigid translation, with motion signals sharing a common motion vector within the spatial region over which the aperture problem is solved. However, this strategy fails for global rotation. Here we show that the human visual system can estimate global rotation directly through spatial pooling of locally ambiguous measurements, without an intervening step that computes local motion vectors. We designed a novel ambiguous global flow stimulus, which is globally as well as locally ambiguous. The global ambiguity implies that the stimulus is simultaneously consistent with both a global rigid translation and an infinite number of global rigid rotations. By the standard view, the motion should always be seen as a global translation, but it appears to shift from translation to rotation as observers shift fixation. This finding indicates that the visual system can estimate local vectors using a global rotation constraint, and suggests that local motion ambiguity may not be resolved until consistencies with multiple global motion patterns are assessed.

  15. Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.

    Directory of Open Access Journals (Sweden)

    Andrea Trochine

    2014-05-01

    Full Text Available The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn. Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi.

  16. Ecosystem service tradeoff analysis reveals the value of marine spatial planning for multiple ocean uses.

    Science.gov (United States)

    White, Crow; Halpern, Benjamin S; Kappel, Carrie V

    2012-03-20

    Marine spatial planning (MSP) is an emerging responsibility of resource managers around the United States and elsewhere. A key proposed advantage of MSP is that it makes tradeoffs in resource use and sector (stakeholder group) values explicit, but doing so requires tools to assess tradeoffs. We extended tradeoff analyses from economics to simultaneously assess multiple ecosystem services and the values they provide to sectors using a robust, quantitative, and transparent framework. We used the framework to assess potential conflicts among offshore wind energy, commercial fishing, and whale-watching sectors in Massachusetts and identify and quantify the value from choosing optimal wind farm designs that minimize conflicts among these sectors. Most notably, we show that using MSP over conventional planning could prevent >$1 million dollars in losses to the incumbent fishery and whale-watching sectors and could generate >$10 billion in extra value to the energy sector. The value of MSP increased with the greater the number of sectors considered and the larger the area under management. Importantly, the framework can be applied even when sectors are not measured in dollars (e.g., conservation). Making tradeoffs explicit improves transparency in decision-making, helps avoid unnecessary conflicts attributable to perceived but weak tradeoffs, and focuses debate on finding the most efficient solutions to mitigate real tradeoffs and maximize sector values. Our analysis demonstrates the utility, feasibility, and value of MSP and provides timely support for the management transitions needed for society to address the challenges of an increasingly crowded ocean environment.

  17. Comparison of multiplicative heterogeneous variance adjustment models for genetic evaluations.

    Science.gov (United States)

    Márkus, Sz; Mäntysaari, E A; Strandén, I; Eriksson, J-Å; Lidauer, M H

    2014-06-01

    Two heterogeneous variance adjustment methods and two variance models were compared in a simulation study. The method used for heterogeneous variance adjustment in the Nordic test-day model, which is a multiplicative method based on Meuwissen (J. Dairy Sci., 79, 1996, 310), was compared with a restricted multiplicative method where the fixed effects were not scaled. Both methods were tested with two different variance models, one with a herd-year and the other with a herd-year-month random effect. The simulation study was built on two field data sets from Swedish Red dairy cattle herds. For both data sets, 200 herds with test-day observations over a 12-year period were sampled. For one data set, herds were sampled randomly, while for the other, each herd was required to have at least 10 first-calving cows per year. The simulations supported the applicability of both methods and models, but the multiplicative mixed model was more sensitive in the case of small strata sizes. Estimation of variance components for the variance models resulted in different parameter estimates, depending on the applied heterogeneous variance adjustment method and variance model combination. Our analyses showed that the assumption of a first-order autoregressive correlation structure between random-effect levels is reasonable when within-herd heterogeneity is modelled by year classes, but less appropriate for within-herd heterogeneity by month classes. Of the studied alternatives, the multiplicative method and a variance model with a random herd-year effect were found most suitable for the Nordic test-day model for dairy cattle evaluation.

  18. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    Directory of Open Access Journals (Sweden)

    Schwend Tyler

    2009-11-01

    Full Text Available Abstract Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC. Genetic studies in zebrafish and mice have established that the Hedgehog (Hh-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE, which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia 12. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1 for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1. Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to

  19. Fine-root responses to fertilization reveal multiple nutrient limitation in a lowland tropical forest.

    Science.gov (United States)

    Wurzburger, Nina; Wright, S Joseph

    2015-08-01

    Questions remain as to which soil nutrients limit primary production in tropical forests. Phosphorus (P) has long been considered the primary limiting element in lowland forests, but recent evidence demonstrates substantial heterogeneity in response to nutrient addition, highlighting a need to understand and diagnose nutrient limitation across diverse forests. Fine-root characteristics including their abundance, functional traits, and mycorrhizal symbionts can be highly responsive to changes in soil nutrients and may help to diagnose nutrient limitation. Here, we document the response of fine roots to long-term nitrogen (N), P, and potassium (K) fertilization in a lowland forest in Panama. Because this experiment has demonstrated that N and K together limit tree growth and P limits fine litter production, we hypothesized that fine roots would also respond to nutrient addition. Specifically we hypothesized that N, P, and K addition would reduce the biomass, diameter, tissue density, and mycorrhizal colonization of fine roots, and increase nutrient concentration in root tissue. Most morphological root traits responded to the single addition of K and the paired addition of N and P, with the greatest response to all three nutrients combined. The addition of N, P, and K together reduced fine-root biomass, length, and tissue density, and increased specific root length, whereas root diameter remained unchanged. Nitrogen addition did not alter root N concentration, but P and K addition increased root P and K concentration, respectively. Mycorrhizal colonization of fine roots declined with N, increased with P, and was unresponsive to K addition. Although plant species composition remains unchanged after 14 years of fertilization, fine-root characteristics responded to N, P, and K addition, providing some of the strongest stand-level responses in this experiment. Multiple soil nutrients regulate fine-root abundance, morphological and chemical traits, and their association

  20. Multiple ITS copies reveal extensive hybridization within Rheum (Polygonaceae, a genus that has undergone rapid radiation.

    Directory of Open Access Journals (Sweden)

    Dongshi Wan

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  1. Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Elisa Schneider

    Full Text Available Neuromyelitis optica (NMO and relapsing-remitting multiple sclerosis (RRMS are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL while rare data are available on deeper intra-retinal layers.To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD and RRMS with focus on the influence of a previous optic neuritis (ON.We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC. Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA was assessed.NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema.Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.

  2. A Collaborative Scheduling Model for the Supply-Hub with Multiple Suppliers and Multiple Manufacturers

    Directory of Open Access Journals (Sweden)

    Guo Li

    2014-01-01

    Full Text Available This paper investigates a collaborative scheduling model in the assembly system, wherein multiple suppliers have to deliver their components to the multiple manufacturers under the operation of Supply-Hub. We first develop two different scenarios to examine the impact of Supply-Hub. One is that suppliers and manufacturers make their decisions separately, and the other is that the Supply-Hub makes joint decisions with collaborative scheduling. The results show that our scheduling model with the Supply-Hub is a NP-complete problem, therefore, we propose an auto-adapted differential evolution algorithm to solve this problem. Moreover, we illustrate that the performance of collaborative scheduling by the Supply-Hub is superior to separate decision made by each manufacturer and supplier. Furthermore, we also show that the algorithm proposed has good convergence and reliability, which can be applicable to more complicated supply chain environment.

  3. Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms.

    Directory of Open Access Journals (Sweden)

    Sara Kangaspeska

    Full Text Available RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60% of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts.

  4. Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control

    Energy Technology Data Exchange (ETDEWEB)

    Burke, Jason R.; Hura, Greg L.; Rubin, Seth M. (UCSC); (LBNL)

    2012-07-18

    Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins. We present the first structures of phosphorylated Rb that reveal the mechanism of its inactivation. S608 phosphorylation orders a flexible 'pocket' domain loop such that it mimics and directly blocks E2F transactivation domain (E2F{sup TD}) binding. T373 phosphorylation induces a global conformational change that associates the pocket and N-terminal domains (RbN). This first multidomain Rb structure demonstrates a novel role for RbN in allosterically inhibiting the E2F{sup TD}-pocket association and protein binding to the pocket 'LxCxE' site. Together, these structures detail the regulatory mechanism for a canonical growth-repressive complex and provide a novel example of how multisite Cdk phosphorylation induces diverse structural changes to influence cell cycle signaling.

  5. Multiple commodities in statistical microeconomics: Model and market

    Science.gov (United States)

    Baaquie, Belal E.; Yu, Miao; Du, Xin

    2016-11-01

    A statistical generalization of microeconomics has been made in Baaquie (2013). In Baaquie et al. (2015), the market behavior of single commodities was analyzed and it was shown that market data provides strong support for the statistical microeconomic description of commodity prices. The case of multiple commodities is studied and a parsimonious generalization of the single commodity model is made for the multiple commodities case. Market data shows that the generalization can accurately model the simultaneous correlation functions of up to four commodities. To accurately model five or more commodities, further terms have to be included in the model. This study shows that the statistical microeconomics approach is a comprehensive and complete formulation of microeconomics, and which is independent to the mainstream formulation of microeconomics.

  6. 3D scene modeling from multiple range views

    Science.gov (United States)

    Sequeira, Vitor; Goncalves, Joao G. M.; Ribeiro, M. Isabel

    1995-09-01

    This paper presents a new 3D scene analysis system that automatically reconstructs the 3D geometric model of real-world scenes from multiple range images acquired by a laser range finder on board of a mobile robot. The reconstruction is achieved through an integrated procedure including range data acquisition, geometrical feature extraction, registration, and integration of multiple views. Different descriptions of the final 3D scene model are obtained: a polygonal triangular mesh, a surface description in terms of planar and biquadratics surfaces, and a 3D boundary representation. Relevant experimental results from the complete 3D scene modeling are presented. Direct applications of this technique include 3D reconstruction and/or update of architectual or industrial plans into a CAD model, design verification of buildings, navigation of autonomous robots, and input to virtual reality systems.

  7. Particle multiplicities and particle ratios in excluded volume model

    CERN Document Server

    Mishra, M

    2008-01-01

    One of the most surprising results is to find that a consistent description of all the experimental results on particle multiplicities and particle ratios obtained from the lowest AGS to the highest RHIC energies is possible within the framework of a thermal statistical model. We propose here a thermodynamically consistent excluded-volume model involving an interacting multi-component hadron gas. We find that the energy dependence of the total multiplicities of strange and non-strange hadrons obtained in this model agrees closely with the experimental results. It indicates that the freeze out volume of the fireball is uniformly the same for all the particles. We have also compared the variation of the particle ratios such as $/, /, K^{-}/K^{+}, \\bar{p}/p, \\bar{\\Lambda}/\\Lambda, \\bar{\\Xi}/\\Xi, \\bar{\\Omega}/\\Omega, /, /, /$ and $/$ with respect to the center-of-mass energy as predicted by our model with the recent experimental data.

  8. A Survey of Health Care Models that Encompass Multiple Departments

    NARCIS (Netherlands)

    Vanberkel, Peter T.; Boucherie, Richardus J.; Hans, Elias W.; Hurink, Johann L.; Litvak, Nelli

    2009-01-01

    In this survey we review quantitative health care models to illustrate the extent to which they encompass multiple hospital departments. The paper provides general overviews of the relationships that exists between major hospital departments and describes how these relationships are accounted for by

  9. A survey of health care models that encompass multiple departments

    NARCIS (Netherlands)

    Vanberkel, P.T.; Boucherie, Richardus J.; Hans, Elias W.; Hurink, Johann L.; Litvak, Nelli

    2009-01-01

    In this survey we review quantitative health care models to illustrate the extent to which they encompass multiple hospital departments. The paper provides general overviews of the relationships that exists between major hospital departments and describes how these relationships are accounted for by

  10. EAE : imperfect but useful models of multiple sclerosis

    NARCIS (Netherlands)

    't Hart, Bert A.; Gran, Bruno; Weissert, Robert

    2011-01-01

    The high failure rate of immunotherapies in multiple sclerosis (MS) clinical trials demonstrates problems in translating new treatment concepts from animal models to the patient. One main reason for this 'immunotherapy gap' is the usage of immunologically immature, microbiologically clean and geneti

  11. Multiple-Model Adaptive Switching Control for Uncertain Multivariable Systems

    NARCIS (Netherlands)

    Baldi, Simone; Battistelli, Giorgio; Mari, Daniele; Mosca, Edoardo; Tesi, Pietro

    2011-01-01

    This paper addresses the problem of controlling an uncertain multi-input multi-output (MIMO) system by means of adaptive switching control schemes. In particular, the paper aims at extending the approach of multiple-model unfalsified adaptive switched control, so far restricted to single-input singl

  12. Geant4 models for simulation of multiple scattering

    CERN Document Server

    Ivanchenko, V N; Maire, M; Urban, L

    2010-01-01

    Recent progress in development of single and multiple scattering models within the Geant4 toolkit is presented. Different options available to users are discussed. The comparisons with the data are shown. The trade of precision versus CPU performance is discussed with the focus on LHC detectors simulation

  13. Fraction Multiplication and Division Models: A Practitioner Reference Paper

    Science.gov (United States)

    Ervin, Heather K.

    2017-01-01

    It is well documented in literature that rational number is an important area of understanding in mathematics. Therefore, it follows that teachers and students need to have an understanding of rational number and related concepts such as fraction multiplication and division. This practitioner reference paper examines models that are important to…

  14. Multiple Imputation of Predictor Variables Using Generalized Additive Models

    NARCIS (Netherlands)

    de Jong, Roel; van Buuren, Stef; Spiess, Martin

    2016-01-01

    The sensitivity of multiple imputation methods to deviations from their distributional assumptions is investigated using simulations, where the parameters of scientific interest are the coefficients of a linear regression model, and values in predictor variables are missing at random. The performanc

  15. Coast-wide recruitment dynamics of Olympia oysters reveal limited synchrony and multiple predictors of failure.

    Science.gov (United States)

    Wasson, Kerstin; Hughes, Brent B; Berriman, John S; Chang, Andrew L; Deck, Anna K; Dinnel, Paul A; Endris, Charlie; Espinoza, Michael; Dudas, Sarah; Ferner, Matthew C; Grosholz, Edwin D; Kimbro, David; Ruesink, Jennifer L; Trimble, Alan C; Vander Schaaf, Dick; Zabin, Chela J; Zacherl, Danielle C

    2016-12-01

    Recruitment of new propagules into a population can be a critical determinant of adult density. We examined recruitment dynamics in the Olympia oyster (Ostrea lurida), a species occurring almost entirely in estuaries. We investigated spatial scales of interannual synchrony across 37 sites in eight estuaries along 2,500 km of Pacific North American coastline, predicting that high vs. low recruitment years would coincide among neighboring estuaries due to shared exposure to regional oceanographic factors. Such synchrony in recruitment has been found for many marine species and some migratory estuarine species, but has never been examined across estuaries in a species that can complete its entire life cycle within the same estuary. To inform ongoing restoration efforts for Olympia oysters, which have declined in abundance in many estuaries, we also investigated predictors of recruitment failure. We found striking contrasts in absolute recruitment rate and frequency of recruitment failure among sites, estuaries, and years. Although we found a positive relationship between upwelling and recruitment, there was little evidence of synchrony in recruitment among estuaries along the coast, and only limited synchrony of sites within estuaries, suggesting recruitment rates are affected more strongly by local dynamics within estuaries than by regional oceanographic factors operating at scales encompassing multiple estuaries. This highlights the importance of local wetland and watershed management for the demography of oysters, and perhaps other species that can complete their entire life cycle within estuaries. Estuaries with more homogeneous environmental conditions had greater synchrony among sites, and this led to the potential for estuary-wide failure when all sites had no recruitment in the same year. Environmental heterogeneity within estuaries may thus buffer against estuary-wide recruitment failure, analogous to the portfolio effect for diversity. Recruitment failure

  16. Multiple measures reveal antiretroviral adherence successes and challenges in HIV-infected Ugandan children.

    Directory of Open Access Journals (Sweden)

    Jessica E Haberer

    Full Text Available BACKGROUND: Adherence to HIV antiretroviral therapy (ART among children in developing settings is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS. Interruptions in MEMS adherence of ≥ 48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = -0.25, p = 0.04. Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6-5.5; p = 0.001, liquid formulation use (AOR 1.4, 95%CI 1.0-2.0; p = 0.04, and caregiver's alcohol use (AOR 3.1, 95%CI 1.8-5.2; p<0.0001. Child's use of co-trimoxazole (AOR 0.5, 95%CI 0.4-0.9; p = 0.009, caregiver's use of ART (AOR 0.6, 95%CI 0.4-0.9; p = 0.03, possible caregiver depression (AOR 0.6, 95%CI 0.4-0.8; p = 0.001, and caregiver feeling ashamed of child's HIV status (AOR 0.5, 95%CI 0.3-0.6; p<0.0001 were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5-11.5; p = 0.009 and caregiver's alcohol use (AOR 5.5, 95%CI 2.8-10.7; p<0.0001 were associated with ≥ 48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1-0.99; p = 0.049 and increasing assets (AOR 0.7, 95%CI 0.6-0.9; p = 0.0007 were protective against these interruptions. CONCLUSIONS/SIGNIFICANCE: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and

  17. Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes.

    Directory of Open Access Journals (Sweden)

    Wayne Chadwick

    Full Text Available The central nervous system normally functions at O(2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O(2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O(2 tensions compared to the cell culture standard of 20% O(2, to investigate their ability to sense and translate this O(2 information to transcriptional activity. Variance of ambient O(2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O(2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O(2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O(2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

  18. Kinetic analyses reveal multiple steps in forming TonB-FhuA complexes from Escherichia coli.

    Science.gov (United States)

    Khursigara, Cezar M; De Crescenzo, Gregory; Pawelek, Peter D; Coulton, James W

    2005-03-08

    FhuA, an outer membrane receptor of Escherichia coli, facilitates transport of hydroxamate siderophores and siderophore-antibiotic conjugates. The cytoplasmic membrane complex TonB-ExbB-ExbD provides energy for transport via the proton motive force. This energy is transduced by protein-protein interactions between TonB and FhuA, but the molecular determinants of these interactions remain uncharacterized. Our analyses of FhuA and two recombinant TonB species by surface plasmon resonance revealed that TonB undergoes a kinetically limiting rearrangement upon initial interaction with FhuA: an intermediate TonB-FhuA complex of 1:1 stoichiometry was detected. The intermediate then recruits a second TonB protein. Addition of ferricrocin, a FhuA-specific ligand, enhanced amounts of the 2:1 complex but was not essential for its formation. To assess the role of the cork domain of FhuA in forming a 2:1 TonB-FhuA complex, we tested a FhuA deletion (residues 21-128) for its ability to interact with TonB. Analytical ultracentrifugation demonstrated that deletion of this region of the cork domain resulted in a 1:1 complex. Furthermore, the high-affinity 2:1 complex requires the N-terminal region of TonB. Together these in vitro experiments establish that TonB-FhuA interactions require sequential steps of kinetically limiting rearrangements. Additionally, domains that contribute to complex formation were identified in TonB and in FhuA.

  19. Historical comparisons reveal multiple drivers of decadal change of an ecosystem engineer at the range edge.

    Science.gov (United States)

    Firth, Louise B; Mieszkowska, Nova; Grant, Lisa M; Bush, Laura E; Davies, Andrew J; Frost, Matthew T; Moschella, Paula S; Burrows, Michael T; Cunningham, Paul N; Dye, Stephen R; Hawkins, Stephen J

    2015-08-01

    Biogenic reefs are important for habitat provision and coastal protection. Long-term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi-quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of

  20. Integrative taxonomy of root-knot nematodes reveals multiple independent origins of mitotic parthenogenesis

    Science.gov (United States)

    Janssen, Toon; Karssen, Gerrit; Topalović, Olivera; Coyne, Danny; Bert, Wim

    2017-01-01

    During sampling of several Coffea arabica plantations in Tanzania severe root galling, caused by a root-knot nematode was observed. From pure cultures, morphology and morphometrics of juveniles and females matched perfectly with Meloidogyne africana, whereas morphology of the males matched identically with those of Meloidogyne decalineata. Based on their Cox1 sequence, however, the recovered juveniles, females and males were confirmed to belong to the same species, creating a taxonomic conundrum. Adding further to this puzzle, re-examination of M. oteifae type material showed insufficient morphological evidence to maintain its status as a separate species. Consequently, M. decalineata and M. oteifae are synonymized with M. africana, which is herewith redescribed based on results of light and scanning electron microscopy, ribosomal and mitochondrial DNA sequences, isozyme electrophoresis, along with bionomic and cytogenetic features. Multi-gene phylogenetic analysis placed M. africana outside of the three major clades, together with M. coffeicola, M. ichinohei and M. camelliae. This phylogenetic position was confirmed by several morphological features, including cellular structure of the spermatheca, egg mass position, perineal pattern and head shape. Moreover, M. africana was found to be a polyphagous species, demonstrating that “early-branching” Meloidogyne spp. are not as oligophagous as had previously been assumed. Cytogenetic information indicates M. africana (2n = 21) and M. ardenensis (2n = 51–54) to be a triploid mitotic parthenogenetic species, revealing at least four independent origins of mitotic parthenogenesis within the genus Meloidogyne. Furthermore, M. mali (n = 12) was found to reproduce by amphimixis, indicating that amphimictic species with a limited number of chromosomes are widespread in the genus, potentially reflecting the ancestral state of the genus. The wide variation in chromosome numbers and associated changes in reproduction modes

  1. Multiple-relaxation-time model for the correct thermohydrodynamic equations.

    Science.gov (United States)

    Zheng, Lin; Shi, Baochang; Guo, Zhaoli

    2008-08-01

    A coupling lattice Boltzmann equation (LBE) model with multiple relaxation times is proposed for thermal flows with viscous heat dissipation and compression work. In this model the fixed Prandtl number and the viscous dissipation problems in the energy equation, which exist in most of the LBE models, are successfully overcome. The model is validated by simulating the two-dimensional Couette flow, thermal Poiseuille flow, and the natural convection flow in a square cavity. It is found that the numerical results agree well with the analytical solutions and/or other numerical results.

  2. Infinite Multiple Membership Relational Modeling for Complex Networks

    DEFF Research Database (Denmark)

    Mørup, Morten; Schmidt, Mikkel Nørgaard; Hansen, Lars Kai

    Learning latent structure in complex networks has become an important problem fueled by many types of networked data originating from practically all fields of science. In this paper, we propose a new non-parametric Bayesian multiplemembership latent feature model for networks. Contrary to existing...... multiplemembership models that scale quadratically in the number of vertices the proposedmodel scales linearly in the number of links admittingmultiple-membership analysis in large scale networks. We demonstrate a connection between the single membership relational model and multiple membership models and show...

  3. Incorporating Student Mobility in Achievement Growth Modeling: A Cross-Classified Multiple Membership Growth Curve Model

    Science.gov (United States)

    Grady, Matthew W.; Beretvas, S. Natasha

    2010-01-01

    Multiple membership random effects models (MMREMs) have been developed for use in situations where individuals are members of multiple higher level organizational units. Despite their availability and the frequency with which multiple membership structures are encountered, no studies have extended the MMREM approach to hierarchical growth curve…

  4. Multiple ontologies in action: composite annotations for biosimulation models.

    Science.gov (United States)

    Gennari, John H; Neal, Maxwell L; Galdzicki, Michal; Cook, Daniel L

    2011-02-01

    There now exists a rich set of ontologies that provide detailed semantics for biological entities of interest. However, there is not (nor should there be) a single source ontology that provides all the necessary semantics for describing biological phenomena. In the domain of physiological biosimulation models, researchers use annotations to convey semantics, and many of these annotations require the use of multiple reference ontologies. Therefore, we have developed the idea of composite annotations that access multiple ontologies to capture the physics-based meaning of model variables. These composite annotations provide the semantic expressivity needed to disambiguate the often-complex features of biosimulation models, and can be used to assist with model merging and interoperability. In this paper, we demonstrate the utility of composite annotations for model merging by describing their use within SemGen, our semantics-based model composition software. More broadly, if orthogonal reference ontologies are to meet their full potential, users need tools and methods to connect and link these ontologies. Our composite annotations and the SemGen tool provide one mechanism for leveraging multiple reference ontologies.

  5. ABCC transporters mediate insect resistance to multiple Bt toxins revealed by bulk segregant analysis.

    Science.gov (United States)

    Park, Youngjin; González-Martínez, Rosa M; Navarro-Cerrillo, Gloria; Chakroun, Maissa; Kim, Yonggyun; Ziarsolo, Pello; Blanca, Jose; Cañizares, Joaquin; Ferré, Juan; Herrero, Salvador

    2014-06-09

    Relatively recent evidence indicates that ABCC2 transporters play a main role in the mode of action of Bacillus thuringiensis (Bt) Cry1A-type proteins. Mapping of major Cry1A resistance genes has linked resistance to the ABCC2 locus in Heliothis virescens, Plutella xylostella, Trichoplusia ni and Bombyx mori, and mutations in this gene have been found in three of these Bt-resistant strains. We have used a colony of Spodoptera exigua (Xen-R) highly resistant to a Bt commercial bioinsecticide to identify regions in the S. exigua genome containing loci for major resistance genes by using bulk segregant analysis (BSA). Results reveal a region containing three genes from the ABCC family (ABBC1, ABBC2 and ABBC3) and a mutation in one of them (ABBC2) as responsible for the resistance of S. exigua to the Bt commercial product and to its key Spodoptera-active ingredients, Cry1Ca. In contrast to all previously described mutations in ABCC2 genes that directly or indirectly affect the extracellular domains of the membrane protein, the ABCC2 mutation found in S. exigua affects an intracellular domain involved in ATP binding. Functional analyses of ABBC2 and ABBC3 support the role of both proteins in the mode of action of Bt toxins in S. exigua. Partial silencing of these genes with dsRNA decreased the susceptibility of wild type larvae to both Cry1Ac and Cry1Ca. In addition, reduction of ABBC2 and ABBC3 expression negatively affected some fitness components and induced up-regulation of arylphorin and repat5, genes that respond to Bt intoxication and that are found constitutively up-regulated in the Xen-R strain. The current results show the involvement of different members of the ABCC family in the mode of action of B. thuringiensis proteins and expand the role of the ABCC2 transporter in B. thuringiensis resistance beyond the Cry1A family of proteins to include Cry1Ca.

  6. Generative models: Human embryonic stem cells and multiple modeling relations.

    Science.gov (United States)

    Fagan, Melinda Bonnie

    2016-04-01

    Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Weibull model of multiplicity distribution in hadron-hadron collisions

    Science.gov (United States)

    Dash, Sadhana; Nandi, Basanta K.; Sett, Priyanka

    2016-06-01

    We introduce the use of the Weibull distribution as a simple parametrization of charged particle multiplicities in hadron-hadron collisions at all available energies, ranging from ISR energies to the most recent LHC energies. In statistics, the Weibull distribution has wide applicability in natural processes that involve fragmentation processes. This provides a natural connection to the available state-of-the-art models for multiparticle production in hadron-hadron collisions, which involve QCD parton fragmentation and hadronization. The Weibull distribution describes the multiplicity data at the most recent LHC energies better than the single negative binomial distribution.

  8. Dynamic force spectroscopy on multiple bonds: experiments and model

    CERN Document Server

    Erdmann, T; Nassoy, P; Schwarz, U S

    2007-01-01

    We probe the dynamic strength of multiple biotin-streptavidin adhesion bonds under linear loading using the biomembrane force probe setup for dynamic force spectroscopy. Measured rupture force histograms are compared to results from a master equation model for the stochastic dynamics of bond rupture under load. This allows us to extract the distribution of the number of initially closed bonds. We also extract the molecular parameters of the adhesion bonds, in good agreement with earlier results from single bond experiments. Our analysis shows that the peaks in the measured histograms are not simple multiples of the single bond values, but follow from a superposition procedure which generates different peak positions.

  9. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    Directory of Open Access Journals (Sweden)

    Jörger Katharina M

    2012-12-01

    Full Text Available Abstract Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH. In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC, statistical parsimony, Bayesian Species Delineation (BPP and Automatic Barcode Gap Discovery (ABGD. The secondary species hypothesis (SSH is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’, resulting in the discovery of a radiation of (at least 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically

  10. DNA barcoding reveals the coral “laboratory-rat”, Stylophora pistillata encompasses multiple identities

    Science.gov (United States)

    Keshavmurthy, Shashank; Yang, Sung-Yin; Alamaru, Ada; Chuang, Yao-Yang; Pichon, Michel; Obura, David; Fontana, Silvia; De Palmas, Stephane; Stefani, Fabrizio; Benzoni, Francesca; MacDonald, Angus; Noreen, Annika M. E.; Chen, Chienshun; Wallace, Carden C.; Pillay, Ruby Moothein; Denis, Vianney; Amri, Affendi Yang; Reimer, James D.; Mezaki, Takuma; Sheppard, Charles; Loya, Yossi; Abelson, Avidor; Mohammed, Mohammed Suleiman; Baker, Andrew C.; Mostafavi, Pargol Ghavam; Suharsono, Budiyanto A.; Chen, Chaolun Allen

    2013-01-01

    Stylophora pistillata is a widely used coral “lab-rat” species with highly variable morphology and a broad biogeographic range (Red Sea to western central Pacific). Here we show, by analysing Cytochorme Oxidase I sequences, from 241 samples across this range, that this taxon in fact comprises four deeply divergent clades corresponding to the Pacific-Western Australia, Chagos-Madagascar-South Africa, Gulf of Aden-Zanzibar-Madagascar, and Red Sea-Persian/Arabian Gulf-Kenya. On the basis of the fossil record of Stylophora, these four clades diverged from one another 51.5-29.6 Mya, i.e., long before the closure of the Tethyan connection between the tropical Indo-West Pacific and Atlantic in the early Miocene (16–24 Mya) and should be recognised as four distinct species. These findings have implications for comparative ecological and/or physiological studies carried out using Stylophora pistillata as a model species, and highlight the fact that phenotypic plasticity, thought to be common in scleractinian corals, can mask significant genetic variation. PMID:23519209

  11. Phenotypic landscape inference reveals multiple evolutionary paths to C4 photosynthesis.

    Science.gov (United States)

    Williams, Ben P; Johnston, Iain G; Covshoff, Sarah; Hibberd, Julian M

    2013-09-28

    C4 photosynthesis has independently evolved from the ancestral C3 pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C3, C4, or intermediate C3-C4 forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C4 phenotype evolved. The alternative evolutionary histories underlying the appearance of C4 photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C4 trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait. DOI:http://dx.doi.org/10.7554/eLife.00961.001.

  12. Hybrid Methods Reveal Multiple Flexibly Linked DNA Polymerases within the Bacteriophage T7 Replisome.

    Science.gov (United States)

    Wallen, Jamie R; Zhang, Hao; Weis, Caroline; Cui, Weidong; Foster, Brittni M; Ho, Chris M W; Hammel, Michal; Tainer, John A; Gross, Michael L; Ellenberger, Tom

    2017-01-03

    The physical organization of DNA enzymes at a replication fork enables efficient copying of two antiparallel DNA strands, yet dynamic protein interactions within the replication complex complicate replisome structural studies. We employed a combination of crystallographic, native mass spectrometry and small-angle X-ray scattering experiments to capture alternative structures of a model replication system encoded by bacteriophage T7. Two molecules of DNA polymerase bind the ring-shaped primase-helicase in a conserved orientation and provide structural insight into how the acidic C-terminal tail of the primase-helicase contacts the DNA polymerase to facilitate loading of the polymerase onto DNA. A third DNA polymerase binds the ring in an offset manner that may enable polymerase exchange during replication. Alternative polymerase binding modes are also detected by small-angle X-ray scattering with DNA substrates present. Our collective results unveil complex motions within T7 replisome higher-order structures that are underpinned by multivalent protein-protein interactions with functional implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. DNA barcoding reveals the coral "laboratory-rat", Stylophora pistillata encompasses multiple identities.

    Science.gov (United States)

    Keshavmurthy, Shashank; Yang, Sung-Yin; Alamaru, Ada; Chuang, Yao-Yang; Pichon, Michel; Obura, David; Fontana, Silvia; De Palmas, Stephane; Stefani, Fabrizio; Benzoni, Francesca; MacDonald, Angus; Noreen, Annika M E; Chen, Chienshun; Wallace, Carden C; Pillay, Ruby Moothein; Denis, Vianney; Amri, Affendi Yang; Reimer, James D; Mezaki, Takuma; Sheppard, Charles; Loya, Yossi; Abelson, Avidor; Mohammed, Mohammed Suleiman; Baker, Andrew C; Mostafavi, Pargol Ghavam; Suharsono, Budiyanto A; Chen, Chaolun Allen

    2013-01-01

    Stylophora pistillata is a widely used coral "lab-rat" species with highly variable morphology and a broad biogeographic range (Red Sea to western central Pacific). Here we show, by analysing Cytochorme Oxidase I sequences, from 241 samples across this range, that this taxon in fact comprises four deeply divergent clades corresponding to the Pacific-Western Australia, Chagos-Madagascar-South Africa, Gulf of Aden-Zanzibar-Madagascar, and Red Sea-Persian/Arabian Gulf-Kenya. On the basis of the fossil record of Stylophora, these four clades diverged from one another 51.5-29.6 Mya, i.e., long before the closure of the Tethyan connection between the tropical Indo-West Pacific and Atlantic in the early Miocene (16-24 Mya) and should be recognised as four distinct species. These findings have implications for comparative ecological and/or physiological studies carried out using Stylophora pistillata as a model species, and highlight the fact that phenotypic plasticity, thought to be common in scleractinian corals, can mask significant genetic variation.

  14. Conservation genomics reveals multiple evolutionary units within Bell’s Vireo (Vireo bellii).

    Science.gov (United States)

    Klicka, Luke B.; Kus, Barbara E.; Title, Pascal O.; Burns, Kevin J.

    2016-01-01

    The Bell’s Vireo (Vireo bellii) is a widespread North American species of bird that has declined since the mid-1960s primarily due to habitat modification. Throughout its range, Bell’s Vireo populations are regulated under varying degrees of protection; however, the species has never been characterized genetically. Therefore, the current taxonomy used to guide management decisions may misrepresent the true evolutionary history for the species. We sequenced 86 individuals for ND2 and genotyped 48 individuals for genome-wide SNPs to identify distinct lineages within Bell’s Vireo. Phylogenetic analyses uncovered two distinct clades that are separated in the arid southwestern United States, near the border of the Chihuahuan and Sonoran Deserts. These clades diverged from each other approximately 1.11–2.04 mya. The timing of diversification, geographic location, and niche modeling of the east/west divergence suggest vicariance as a mode of diversification for these two lineages. Analyses of the SNP dataset provided additional resolution and indicated the Least Bell’s Vireo populations are a distinct evolutionary lineage. Our genetic evidence, together with information from morphology and behavior, suggests that the Bell’s Vireo complex involves two species, each containing two separate subspecies. This new information has implications for the federal, state and other listing status of Bell’s Vireo throughout its range.

  15. Multi-gene phylogenetic analysis reveals the multiple origin and evolution of mangrove physiological traits through exaptation

    Science.gov (United States)

    Sahu, Sunil Kumar; Singh, Reena; Kathiresan, Kandasamy

    2016-12-01

    Mangroves are taxonomically diverse group of salt-tolerant, mainly arboreal, flowering plants that grow in tropical and sub-tropical regions and have adapted themselves to thrive in such obdurate surroundings. While evolution is often understood exclusively in terms of adaptation, innovation often begins when a feature adapted for one function is co-opted for a different purpose and the co-opted features are called exaptations. Thus, one of the fundamental issues is what features of mangroves have evolved through exaptation. We attempt to address these questions through molecular phylogenetic approach using chloroplast and nuclear markers. First, we determined if these mangroves specific traits have evolved multiple times in the phylogeny. Once the multiple origins were established, we then looked at related non-mangrove species for characters that could have been co-opted by mangrove species. We also assessed the efficacy of these molecular sequences in distinguishing mangroves at the species level. This study revealed the multiple origin of mangroves and shed light on the ancestral characters that might have led certain lineages of plants to adapt to estuarine conditions and also traces the evolutionary history of mangroves and hitherto unexplained theory that mangroves traits (aerial roots and viviparous propagules) evolved as a result of exaptation rather than adaptation to saline habitats.

  16. Neuroprotection in a novel mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Katie Lidster

    Full Text Available Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment.

  17. Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways.

    Directory of Open Access Journals (Sweden)

    Debajyoti Ghosh

    Full Text Available Several studies have identified genes that are differentially expressed in atopic dermatitis (AD compared to normal skin. However, there is also considerable variation in the list of differentially expressed genes (DEGs reported by different groups and the exact cause of AD is still not fully understood. Using a rank-based approach, we analyzed gene expression data from five different microarray studies, comprising a total of 127 samples and more than 250,000 transcripts. A total of 89 AD gene expression signatures '89ADGES', including FLG gene, were identified to show dysregulation consistently across these studies. Using a Support Vector Machine, we showed that the '89ADGES' discriminates AD from normal skin with 98% predictive accuracy. Functional annotation of these genes implicated their roles in immune responses (e.g., betadefensin, microseminoprotein, keratinocyte differentiation/epidermal development (e.g., FLG, CORIN, AQP, LOR, KRT16, inflammation (e.g., IL37, IL27RA, CCL18 and lipid metabolism (e.g., AKR1B10, FAD7, FAR2. Subsequently, we validated a subset of signature genes using quantitative PCR in a mouse model. Using a bioinformatic approach, we identified keratinocyte pathway over-represented (P = <0.0006 among the 89 signature genes. Keratinocytes are known to play a major role in barrier function due to their location in the epidermis. Our result suggests that besides immune- mediated pathway, skin barrier pathways such as the keratinocyte differentiation pathway play a key role in AD pathogenesis. A better understanding of the role of keratinocytes in AD will be important for developing novel "barrier therapy" for this disease.

  18. More ways than one: ERPs reveal multiple familiarity signals in the word frequency mirror effect.

    Science.gov (United States)

    Bridger, Emma K; Bader, Regine; Mecklinger, Axel

    2014-05-01

    Recent dual-process models of the word frequency mirror effect place absolute familiarity, an item׳s baseline familiarity at a given time point, as responsible for false alarm differences and recollection for hit rate differences between high and low frequency items. One of the earliest dual-process propositions, however, posits an additional relative familiarity mechanism which is sensitive to recent presentation but relative to the absolute familiarity of a particular item (Mandler, 1980). In this study, it was possible to map these three mechanisms onto known event-related potential (ERP) effects in an old/new recognition task with high and low frequency words. Contrasts between ERPs elicited by high and low frequency new items were assumed to index absolute familiarity, and the distribution of this effect from 300 to 600ms was topographically distinct from a temporally-overlapping midfrontally-distributed old/new effect which was larger for low than high frequency words, as would be expected from a relative familiarity mechanism. A later left parietal old/new effect, strongly linked to recollection, was only present for low frequency items. These frequency-sensitive amplitude differences for both old/new effects disappeared in a second recognition task in which old/new decisions were made under a time constraint, although the posterior absolute familiarity effect remained unaffected by the speeding of responses. The data support the assertion that three distinct recognition processes are affected by word frequency in recognition memory tasks, and the qualitatively distinct distributions associated with the two familiarity contrasts support the presence of two cognitively distinct familiarity mechanisms.

  19. Manipulation of Karyotype in Caenorhabditis elegans Reveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis.

    Science.gov (United States)

    Roelens, Baptiste; Schvarzstein, Mara; Villeneuve, Anne M

    2015-12-01

    Meiotic chromosome segregation requires pairwise association between homologs, stabilized by the synaptonemal complex (SC). Here, we investigate factors contributing to pairwise synapsis by investigating meiosis in polyploid worms. We devised a strategy, based on transient inhibition of cohesin function, to generate polyploid derivatives of virtually any Caenorhabditis elegans strain. We exploited this strategy to investigate the contribution of recombination to pairwise synapsis in tetraploid and triploid worms. In otherwise wild-type polyploids, chromosomes first sort into homolog groups, then multipartner interactions mature into exclusive pairwise associations. Pairwise synapsis associations still form in recombination-deficient tetraploids, confirming a propensity for synapsis to occur in a strictly pairwise manner. However, the transition from multipartner to pairwise association was perturbed in recombination-deficient triploids, implying a role for recombination in promoting this transition when three partners compete for synapsis. To evaluate the basis of synapsis partner preference, we generated polyploid worms heterozygous for normal sequence and rearranged chromosomes sharing the same pairing center (PC). Tetraploid worms had no detectable preference for identical partners, indicating that PC-adjacent homology drives partner choice in this context. In contrast, triploid worms exhibited a clear preference for identical partners, indicating that homology outside the PC region can influence partner choice. Together, our findings, suggest a two-phase model for C. elegans synapsis: an early phase, in which initial synapsis interactions are driven primarily by recombination-independent assessment of homology near PCs and by a propensity for pairwise SC assembly, and a later phase in which mature synaptic interactions are promoted by recombination.

  20. Multiplicative models for survival percentiles: estimating percentile ratios and multiplicative interaction in the metric of time

    Directory of Open Access Journals (Sweden)

    Andrea Bellavia

    2016-09-01

    Full Text Available Evaluating percentiles of survival was proposed as a possible method to analyze time-to-event outcomes. This approach sets the cumulative risk of the event of interest to a specific proportion and evaluates the time by which this proportion is attainedIn this context, exposure-outcome associations can be expressed in terms of differences in survival percentiles, expressing the difference in survival time by which different subgroups of the study population experience the same proportion of events, or in terms of percentile ratios, expressing the strength of the exposure in accelerating the time to the event. Additive models for conditional survival percentiles have been introduced, and their use to estimate multivariable-adjusted percentile differences, and additive interaction on the metric of time has been described. On the other hand, the percentile ratio has never been fully described, neither statistical methods have been presented for its models-based estimation. To bridge this gap, we provide a detailed presentation of the percentile ratio as a relative measure to assess exposure-outcome associations in the context of time-to-event analysis, discussing its interpretation and advantages. We then introduce multiplicative statistical models for conditional survival percentiles, and present their use in estimating percentile ratios and multiplicative interactions in the metric of time. The introduction of multiplicative models for survival percentiles allows researchers to apply this approach in a large variety of context where multivariable adjustment is required, enriching the potentials of the percentile approach as a flexible and valuable tool to evaluate time-to-event outcomes in medical research.

  1. Forecasting relativistic electron flux using dynamic multiple regression models

    Directory of Open Access Journals (Sweden)

    H.-L. Wei

    2011-02-01

    Full Text Available The forecast of high energy electron fluxes in the radiation belts is important because the exposure of modern spacecraft to high energy particles can result in significant damage to onboard systems. A comprehensive physical model of processes related to electron energisation that can be used for such a forecast has not yet been developed. In the present paper a systems identification approach is exploited to deduce a dynamic multiple regression model that can be used to predict the daily maximum of high energy electron fluxes at geosynchronous orbit from data. It is shown that the model developed provides reliable predictions.

  2. Modeling transcriptional networks in Drosophila development at multiple scales.

    Science.gov (United States)

    Wunderlich, Zeba; DePace, Angela H

    2011-12-01

    Quantitative models of developmental processes can provide insights at multiple scales. Ultimately, models may be particularly informative for key questions about network level behavior during development such as how does the system respond to environmental perturbation, or operate reliably in different genetic backgrounds? The transcriptional networks that pattern the Drosophila embryo have been the subject of numerous quantitative experimental studies coupled to modeling frameworks in recent years. In this review, we describe three studies that consider these networks at different levels of molecular detail and therefore result in different types of insights. We also discuss other developmental transcriptional networks operating in Drosophila, with the goal of highlighting what additional insights they may provide.

  3. S-UTD-CH model in multiple diffractions

    Science.gov (United States)

    Baris Tabakcioglu, Mehmet

    2016-05-01

    The propagation of electromagnetic waves in empty space is an extremely simplified case. Thus, the significant question is how an electromagnetic wave propagates in an environment with obstacles such as buildings, trees or hills. Electromagnetic waves are partially reflected and partially diffracted from these obstacles. To predict the relative path loss of electromagnetic waves at the receiving position, many electromagnetic-wave propagation models have been proposed. These propagation models can be classified into models based on numerical integration and those based on ray tracing. Uniform theory of diffraction (UTD) and slope-UTD (S-UTD) models are ray-tracing-based propagation models and are briefly explained in this paper. In addition, detailed information is provided about the improved slope UTD model, which is called the S-UTD with Convex Hull (S-UTD-CH) model. The fundamentals of the S-UTD-CH model are the S-UTD, convex hull and Fresnel zone concept. In particular, the S-UTD-CH model can be applied to multiple diffraction scenarios in the transition region. Moreover, the S-UTD-CH model is considered an optimum model in terms of its accuracy and calculation or computation time. Widespread simulation results are provided to compare the models based on theoretical rays in terms of prediction accuracy and computation time. To compare these models, different operation frequencies and transmitting antenna heights are considered by using a high-performance computing technique.

  4. Scenario-based modeling for multiple allocation hub location problem under disruption risk: multiple cuts Benders decomposition approach

    Science.gov (United States)

    Yahyaei, Mohsen; Bashiri, Mahdi

    2017-03-01

    The hub location problem arises in a variety of domains such as transportation and telecommunication systems. In many real-world situations, hub facilities are subject to disruption. This paper deals with the multiple allocation hub location problem in the presence of facilities failure. To model the problem, a two-stage stochastic formulation is developed. In the proposed model, the number of scenarios grows exponentially with the number of facilities. To alleviate this issue, two approaches are applied simultaneously. The first approach is to apply sample average approximation to approximate the two stochastic problem via sampling. Then, by applying the multiple cuts Benders decomposition approach, computational performance is enhanced. Numerical studies show the effective performance of the SAA in terms of optimality gap for small problem instances with numerous scenarios. Moreover, performance of multi-cut Benders decomposition is assessed through comparison with the classic version and the computational results reveal the superiority of the multi-cut approach regarding the computational time and number of iterations.

  5. Global Sensitivity Analysis for Multiple Scenarios and Models of Nitrogen Processes

    Science.gov (United States)

    Chen, Z.; Shi, L.; Ye, M.

    2015-12-01

    Modeling nitrogen process in soil is a long-lasting challenge partly because of the uncertainties from parameters, models and scenarios. It may be difficult to identify a suitable model and its corresponding parameters.This study assesses the global sensitivity indices for parameters of multiple models and scenarios on nitrogen processes. The majority of existing nitrogen dynamics models consider nitrification and denitrification as a first-order decay process or a Michaelis-Menten model, while various reduction functions are used to reflect the impact of environmental soil conditions. To determine the model uncertainty, 9 alternative models were designed based on NP2D model in this study. These models have the similar descriptions of nitrogen process but are different in the cal reduction functions of soil water and temperature. A global sensitivity analysis of each models under various scenarios was evaluated. Results show that in our synthetic cases of nitrogen transport and transformation, the global sensitivity indices vary between each models and scenarios. Larger indices for parameters of nitrification are obtained than the ones of denitrification in 6 models, while an inverse relationship is revealed in the rest 3 models. Parameters of soil temperature reduction functions are more sensitive than those of soil water reduction functions. When the soil water and temperature increase separately or together, parameters of denitrification gain their sensitivity, but the indices for parameters of soil temperature reduction functions decrease simultaneously. Our results indicate that identifying important parameters may be biased if ignoring the model and scenario uncertainties. This problem can be resolved by using the global sensitivity indices for multiple models and multiple scenarios. The new indices is useful to determine the relative contributions from different models and scenarios.

  6. A PDP model of the simultaneous perception of multiple objects

    Science.gov (United States)

    Henderson, Cynthia M.; McClelland, James L.

    2011-06-01

    Illusory conjunctions in normal and simultanagnosic subjects are two instances where the visual features of multiple objects are incorrectly 'bound' together. A connectionist model explores how multiple objects could be perceived correctly in normal subjects given sufficient time, but could give rise to illusory conjunctions with damage or time pressure. In this model, perception of two objects benefits from lateral connections between hidden layers modelling aspects of the ventral and dorsal visual pathways. As with simultanagnosia, simulations of dorsal lesions impair multi-object recognition. In contrast, a large ventral lesion has minimal effect on dorsal functioning, akin to dissociations between simple object manipulation (retained in visual form agnosia and semantic dementia) and object discrimination (impaired in these disorders) [Hodges, J.R., Bozeat, S., Lambon Ralph, M.A., Patterson, K., and Spatt, J. (2000), 'The Role of Conceptual Knowledge: Evidence from Semantic Dementia', Brain, 123, 1913-1925; Milner, A.D., and Goodale, M.A. (2006), The Visual Brain in Action (2nd ed.), New York: Oxford]. It is hoped that the functioning of this model might suggest potential processes underlying dorsal and ventral contributions to the correct perception of multiple objects.

  7. A Multiple Reaction Modelling Framework for Microbial Electrochemical Technologies

    Science.gov (United States)

    Oyetunde, Tolutola; Sarma, Priyangshu M.; Ahmad, Farrukh; Rodríguez, Jorge

    2017-01-01

    A mathematical model for the theoretical evaluation of microbial electrochemical technologies (METs) is presented that incorporates a detailed physico-chemical framework, includes multiple reactions (both at the electrodes and in the bulk phase) and involves a variety of microbial functional groups. The model is applied to two theoretical case studies: (i) A microbial electrolysis cell (MEC) for continuous anodic volatile fatty acids (VFA) oxidation and cathodic VFA reduction to alcohols, for which the theoretical system response to changes in applied voltage and VFA feed ratio (anode-to-cathode) as well as membrane type are investigated. This case involves multiple parallel electrode reactions in both anode and cathode compartments; (ii) A microbial fuel cell (MFC) for cathodic perchlorate reduction, in which the theoretical impact of feed flow rates and concentrations on the overall system performance are investigated. This case involves multiple electrode reactions in series in the cathode compartment. The model structure captures interactions between important system variables based on first principles and provides a platform for the dynamic description of METs involving electrode reactions both in parallel and in series and in both MFC and MEC configurations. Such a theoretical modelling approach, largely based on first principles, appears promising in the development and testing of MET control and optimization strategies. PMID:28054959

  8. An integrated modelling framework for neural circuits with multiple neuromodulators

    Science.gov (United States)

    Vemana, Vinith

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

  9. A Multiple Model Approach to Modeling Based on Fuzzy Support Vector Machines

    Institute of Scientific and Technical Information of China (English)

    冯瑞; 张艳珠; 宋春林; 邵惠鹤

    2003-01-01

    A new multiple models(MM) approach was proposed to model complex industrial process by using Fuzzy Support Vector Machines (F SVMs). By applying the proposed approach to a pH neutralization titration experi-ment, F_SVMs MM not only provides satisfactory approximation and generalization property, but also achieves superior performance to USOCPN multiple modeling method and single modeling method based on standard SVMs.

  10. Modelling of Yeast Mating Reveals Robustness Strategies for Cell-Cell Interactions.

    Directory of Open Access Journals (Sweden)

    Weitao Chen

    2016-07-01

    Full Text Available Mating of budding yeast cells is a model system for studying cell-cell interactions. Haploid yeast cells secrete mating pheromones that are sensed by the partner which responds by growing a mating projection toward the source. The two projections meet and fuse to form the diploid. Successful mating relies on precise coordination of dynamic extracellular signals, signaling pathways, and cell shape changes in a noisy background. It remains elusive how cells mate accurately and efficiently in a natural multi-cell environment. Here we present the first stochastic model of multiple mating cells whose morphologies are driven by pheromone gradients and intracellular signals. Our novel computational framework encompassed a moving boundary method for modeling both a-cells and α-cells and their cell shape changes, the extracellular diffusion of mating pheromones dynamically coupled with cell polarization, and both external and internal noise. Quantification of mating efficiency was developed and tested for different model parameters. Computer simulations revealed important robustness strategies for mating in the presence of noise. These strategies included the polarized secretion of pheromone, the presence of the α-factor protease Bar1, and the regulation of sensing sensitivity; all were consistent with data in the literature. In addition, we investigated mating discrimination, the ability of an a-cell to distinguish between α-cells either making or not making α-factor, and mating competition, in which multiple a-cells compete to mate with one α-cell. Our simulations were consistent with previous experimental results. Moreover, we performed a combination of simulations and experiments to estimate the diffusion rate of the pheromone a-factor. In summary, we constructed a framework for simulating yeast mating with multiple cells in a noisy environment, and used this framework to reproduce mating behaviors and to identify strategies for robust cell

  11. Heterogeneity in DNA multiple alignments: modeling, inference, and applications in motif finding.

    Science.gov (United States)

    Chen, Gong; Zhou, Qing

    2010-09-01

    Transcription factors bind sequence-specific sites in DNA to regulate gene transcription. Identifying transcription factor binding sites (TFBSs) is an important step for understanding gene regulation. Although sophisticated in modeling TFBSs and their combinatorial patterns, computational methods for TFBS detection and motif finding often make oversimplified homogeneous model assumptions for background sequences. Since nucleotide base composition varies across genomic regions, it is expected to be helpful for motif finding to incorporate the heterogeneity into background modeling. When sequences from multiple species are utilized, variation in evolutionary conservation violates the common assumption of an identical conservation level in multiple alignments. To handle both types of heterogeneity, we propose a generative model in which a segmented Markov chain is used to partition a multiple alignment into regions of homogeneous nucleotide base composition and a hidden Markov model (HMM) is employed to account for different conservation levels. Bayesian inference on the model is developed via Gibbs sampling with dynamic programming recursions. Simulation studies and empirical evidence from biological data sets reveal the dramatic effect of background modeling on motif finding, and demonstrate that the proposed approach is able to achieve substantial improvements over commonly used background models.

  12. Multiple flux difference effect in the lattice hydrodynamic model

    Institute of Scientific and Technical Information of China (English)

    Wang Tao; Gao Zi-You; Zhao Xiao-Mei

    2012-01-01

    Considering the effect of multiple flux difference,an extended lattice model is proposed to improve the stability of traffic flow.The stability condition of the new model is obtained by using linear stability theory.The theoretical analysis result shows that considering the flux difference effect ahead can stabilize traffic flow.The nonlinear analysis is also conducted by using a reductive perturbation method.The modified KdV (mKdV) equation near the critical point is derived and the kink-antikink solution is obtained from the mKdV equation.Numerical simulation results show that the multiple flux difference effect can suppress the traffic jam considerably,which is in line with the analytical result.

  13. Weibull model of Multiplicity Distribution in hadron-hadron collisions

    CERN Document Server

    Dash, Sadhana

    2014-01-01

    We introduce the Weibull distribution as a simple parametrization of charged particle multiplicities in hadron-hadron collisions at all available energies, ranging from ISR energies to the most recent LHC energies. In statistics, the Weibull distribution has wide applicability in natural processes involving fragmentation processes. This gives a natural connection to the available state-of-the-art models for multi-particle production in hadron hadron collisions involving QCD parton fragmentation and hadronization.

  14. Impact of festival factor on electric quantity multiplication forecast model

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This research aims to improve the forecasting precision of electric quantity. It is discovered that the total electricity consumption considerably increased during the Spring Festival by the analysis of the electric quantity time series from 2002 to 2007 in Shandong province. The festival factor is ascertained to be one of the important seasonal factors affecting the electric quantity fluctuations, and the multiplication model for forecasting is improved by introducing corresponding variables and parameters...

  15. Multiple Potts Models Coupled to Two-Dimensional Quantum Gravity

    CERN Document Server

    Baillie, C F

    1992-01-01

    We perform Monte Carlo simulations using the Wolff cluster algorithm of {\\it multiple} $q=2,3,4$ state Potts models on dynamical phi-cubed graphs of spherical topology in order to investigate the $c>1$ region of two-dimensional quantum gravity. Contrary to naive expectation we find no obvious signs of pathological behaviour for $c>1$. We discuss the results in the light of suggestions that have been made for a modified DDK ansatz for $c>1$.

  16. Multiple Potts models coupled to two-dimensional quantum gravity

    Science.gov (United States)

    Baillie, C. F.; Johnston, D. A.

    1992-07-01

    We perform Monte Carlo simulations using the Wolff cluster algorithm of multiple q=2, 3, 4 state Potts models on dynamical phi-cubed graphs of spherical topology in order to investigate the c>1 region of two-dimensional quantum gravity. Contrary to naive expectation we find no obvious signs of pathological behaviour for c>1. We discuss the results in the light of suggestions that have been made for a modified DDK ansatz for c>1.

  17. A galaxy-halo model for multiple cosmological tracers

    Science.gov (United States)

    Bull, Philip

    2017-10-01

    The information extracted from large galaxy surveys with the likes of DES, DESI, Euclid, LSST, SKA, and WFIRST will be greatly enhanced if the resultant galaxy catalogues can be cross-correlated with one another. Predicting the nature of the information gain, and developing the tools to realize it, depends on establishing a consistent model of how the galaxies detected by each survey trace the same underlying matter distribution. Existing analytic methods, such as halo occupation distribution modelling, are not well suited for this task, and can suffer from ambiguities and tuning issues when applied to multiple tracers. In this paper, we take the first step towards constructing an alternative that provides a common model for the connection between galaxies and dark matter haloes across a wide range of wavelengths (and thus tracer populations). This is based on a chain of parametrized statistical distributions that model the connection between (i) halo mass and bulk physical properties of galaxies, such as star formation rate; and (ii) those same physical properties and a variety of emission processes. The result is a flexible parametric model that allows analytic halo model calculations of one-point functions to be carried out for multiple tracers, as well as providing semi realistic galaxy properties for fast mock catalogue generation.

  18. INTERACTING MULTIPLE MODEL ALGORITHM BASED ON JOINT LIKELIHOOD ESTIMATION

    Institute of Scientific and Technical Information of China (English)

    Sun Jie; Jiang Chaoshu; Chen Zhuming; Zhang Wei

    2011-01-01

    A novel approach is proposed for the estimation of likelihood on Interacting Multiple-Model (IMM) filter.In this approach,the actual innovation,based on a mismatched model,can be formulated as sum of the theoretical innovation based on a matched model and the distance between matched and mismatched models,whose probability distributions are known.The joint likelihood of innovation sequence can be estimated by convolution of the two known probability density functions.The likelihood of tracking models can be calculated by conditional probability formula.Compared with the conventional likelihood estimation method,the proposed method improves the estimation accuracy of likelihood and robustness of IMM,especially when maneuver occurs.

  19. Probability-summation model of multiple laser-exposure effects.

    Science.gov (United States)

    Menendez, A R; Cheney, F E; Zuclich, J A; Crump, P

    1993-11-01

    A probability-summation model is introduced to provide quantitative criteria for discriminating independent from interactive effects of multiple laser exposures on biological tissue. Data that differ statistically from predictions of the probability-summation model indicate the action of sensitizing (synergistic/positive) or desensitizing (hardening/negative) biophysical interactions. Interactions are indicated when response probabilities vary with changes in the spatial or temporal separation of exposures. In the absence of interactions, probability-summation parsimoniously accounts for "cumulative" effects. Data analyzed using the probability-summation model show instances of both sensitization and desensitization of retinal tissue by laser exposures. Other results are shown to be consistent with probability-summation. The relevance of the probability-summation model to previous laser-bioeffects studies, models, and safety standards is discussed and an appeal is made for improved empirical estimates of response probabilities for single exposures.

  20. Joint modeling of longitudinal data in multiple behavioral change.

    Science.gov (United States)

    Charnigo, Richard; Kryscio, Richard; Bardo, Michael T; Lynam, Donald; Zimmerman, Rick S

    2011-06-01

    Multiple behavioral change is an exciting and evolving research area, albeit one that presents analytic challenges to investigators. This manuscript considers the problem of modeling jointly trajectories for two or more possibly non-normally distributed dependent variables, such as marijuana smoking and risky sexual activity, collected longitudinally. Of particular scientific interest is applying such modeling to elucidate the nature of the interaction, if any, between an intervention and personal characteristics, such as sensation seeking and impulsivity. The authors describe three analytic approaches: generalized linear mixed modeling, group-based trajectory modeling, and latent growth curve modeling. In particular, the authors identify identify the strengths and weaknesses of these analytic approaches and assess their impact (or lack thereof) on the psychological and behavioral science literature. The authors also compare what investigators have been doing analytically versus what they might want to be doing in the future and discuss the implications for basic and translational research.

  1. A tactical supply chain planning model with multiple flexibility options

    DEFF Research Database (Denmark)

    Esmaeilikia, Masoud; Fahimnia, Behnam; Sarkis, Joeseph

    2016-01-01

    Supply chain flexibility is widely recognized as an approach to manage uncertainty. Uncertainty in the supply chain may arise from a number of sources such as demand and supply interruptions and lead time variability. A tactical supply chain planning model with multiple flexibility options...... incorporated in sourcing, manufacturing and logistics functions can be used for the analysis of flexibility adjustment in an existing supply chain. This paper develops such a tactical supply chain planning model incorporating a realistic range of flexibility options. A novel solution method is designed...

  2. Automatic Generation of 3D Building Models with Multiple Roofs

    Institute of Scientific and Technical Information of China (English)

    Kenichi Sugihara; Yoshitugu Hayashi

    2008-01-01

    Based on building footprints (building polygons) on digital maps, we are proposing the GIS and CG integrated system that automatically generates 3D building models with multiple roofs. Most building polygons' edges meet at right angles (orthogonal polygon). The integrated system partitions orthogonal building polygons into a set of rectangles and places rectangular roofs and box-shaped building bodies on these rectangles. In order to partition an orthogonal polygon, we proposed a useful polygon expression in deciding from which vertex a dividing line is drawn. In this paper, we propose a new scheme for partitioning building polygons and show the process of creating 3D roof models.

  3. Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to the Dermis.

    Science.gov (United States)

    Gonzalez, Rodrigo J; Weening, Eric H; Lane, M Chelsea; Miller, Virginia L

    2015-07-01

    Vector-borne pathogens are inoculated in the skin of mammals, most likely in the dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in many fields, including Yersinia pestis pathogenesis. We expand on a previous report where we implemented intradermal (i.d.) inoculations to study bacterial dissemination during bubonic plague and compare this model with an s.c. We found that i.d. inoculations result in faster kinetics of infection and that bacterial dose influenced mouse survival after i.d. but not s.c. inoculation. Moreover, a deletion mutant of rovA, previously shown to be moderately attenuated in the s.c. model, was severely attenuated in the i.d. Lastly, based on previous observations where a population bottleneck from the skin to lymph nodes was observed after i.d., but not after s.c., inoculations, we used the latter model as a strategy to identify an additional bottleneck in bacterial dissemination from lymph nodes to the bloodstream. Our data indicate that the more biologically relevant i.d. model of bubonic plague differs significantly from the s.c. model in multiple aspects of infection. These findings reveal adaptations of Y. pestis to the dermis and how these adaptations can define the progression of disease. They also emphasize the importance of using a relevant route of infection when addressing host-pathogen interactions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. A Galaxy-Halo Model for Multiple Cosmological Tracers

    CERN Document Server

    Bull, Philip

    2016-01-01

    The information extracted from large galaxy surveys with the likes of DES, DESI, Euclid, LSST, SKA, and WFIRST will be greatly enhanced if the resultant galaxy catalogues can be cross-correlated with one another. Predicting the nature of the information gain, and developing the tools to realise it, depends on establishing a consistent model of how the galaxies detected by each survey trace the same underlying matter distribution. Existing analytic methods, such as halo occupation distribution (HOD) modelling, are not well-suited for this task, and can suffer from ambiguities and tuning issues when applied to multiple tracers. We construct a simple alternative that provides a common model for the connection between galaxies and dark matter halos across a wide range of wavelengths (and thus tracer populations). This is based on a chain of parametrised statistical distributions that model the connection between (a) halo mass and bulk physical properties of galaxies, such as star-formation rate; and (b) those sam...

  5. Oscillations and multiple steady states in active membrane transport models.

    Science.gov (United States)

    Vieira, F M; Bisch, P M

    1994-01-01

    The dynamic behavior of some non-linear extensions of the six-state alternating access model for active membrane transport is investigated. We use stoichio-metric network analysis to study the stability of steady states. The bifurcation analysis has been done through standard numerical methods. For the usual six-state model we have proved that there is only one steady state, which is globally asymptotically stable. When we added an autocatalytic step we found self-oscillations. For the competition between a monomer cycle and a dimer cycle, with steps of dimer formation, we have also found self-oscillations. We have also studied models involving the formation of a complex with other molecules. The addition of two steps for formation of a complex of the monomer with another molecule does not alter either the number or the stability of steady states of the basic six-state model. The model which combines the formation of a complex with an autocatalytic step shows both self-oscillations and multiple steady states. The results lead us to conclude that oscillations could be produced by active membrane transport systems if the transport cycle contains a sufficiently large number of steps (six in the present case) and is coupled to at least one autocatalytic reaction,. Oscillations are also predicted when the monomer cycle is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a simplification of the model involving competition between monomer and dimer cycles, which seems to be a more realistic description of biological systems. A self-regulation mechanism of the pumps, related to the multiple stationary states, is expected only for a combined effect of autocatalysis and formation of complexes with other molecules. Within the six-state model this model also leads to oscillation.

  6. Integrated metabolic modelling reveals cell-type specific epigenetic control points of the macrophage metabolic network.

    Science.gov (United States)

    Pacheco, Maria Pires; John, Elisabeth; Kaoma, Tony; Heinäniemi, Merja; Nicot, Nathalie; Vallar, Laurent; Bueb, Jean-Luc; Sinkkonen, Lasse; Sauter, Thomas

    2015-10-19

    The reconstruction of context-specific metabolic models from easily and reliably measurable features such as transcriptomics data will be increasingly important in research and medicine. Current reconstruction methods suffer from high computational effort and arbitrary threshold setting. Moreover, understanding the underlying epigenetic regulation might allow the identification of putative intervention points within metabolic networks. Genes under high regulatory load from multiple enhancers or super-enhancers are known key genes for disease and cell identity. However, their role in regulation of metabolism and their placement within the metabolic networks has not been studied. Here we present FASTCORMICS, a fast and robust workflow for the creation of high-quality metabolic models from transcriptomics data. FASTCORMICS is devoid of arbitrary parameter settings and due to its low computational demand allows cross-validation assays. Applying FASTCORMICS, we have generated models for 63 primary human cell types from microarray data, revealing significant differences in their metabolic networks. To understand the cell type-specific regulation of the alternative metabolic pathways we built multiple models during differentiation of primary human monocytes to macrophages and performed ChIP-Seq experiments for histone H3 K27 acetylation (H3K27ac) to map the active enhancers in macrophages. Focusing on the metabolic genes under high regulatory load from multiple enhancers or super-enhancers, we found these genes to show the most cell type-restricted and abundant expression profiles within their respective pathways. Importantly, the high regulatory load genes are associated to reactions enriched for transport reactions and other pathway entry points, suggesting that they are critical regulatory control points for cell type-specific metabolism. By integrating metabolic modelling and epigenomic analysis we have identified high regulatory load as a common feature of metabolic

  7. Multiplicative ARMA models to generate hourly series of global irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mora-Lopez, L. [Universidad de Malaga (Spain). Dpto. Lenguajes y C. Computacion; Sidrach-de-Cardona, M. [Universidad de Malaga (Spain). Dpto. Fisica Aplicada

    1998-11-01

    A methodology to generate hourly series of global irradiation is proposed. The only input parameter which is required is the monthly mean value of daily global irradiation, which is available for most locations. The procedure to obtain new series is based on the use of a multiplicative autoregressive moving-average statistical model for time series with regular and seasonal components. The multiplicative nature of these models enables capture of the two types of relationships observed in recorded hourly series of global irradiation: on the one hand, the relationship between the value at one hour and the value at the previous hour; and on the other hand, the relationship between the value at one hour in one day and the value at the same hour in the previous day. In this paper the main drawback which arises when using these models to generate new series is solved: namely, the need for available recorded series in order to obtain the three parameters contained in the statistical ARMA model which is proposed (autoregressive coefficient, moving-average coefficient and variance of the error term). Specifically, expressions which enable estimation of these parameters using only monthly mean values of daily global irradiation are proposed in this paper. (author)

  8. Adaptive mixture observation models for multiple object tracking

    Institute of Scientific and Technical Information of China (English)

    CUI Peng; SUN LiFeng; YANG ShiQiang

    2009-01-01

    Multiple object tracking (MOT) poses many difficulties to conventional well-studied single object track-ing (SOT) algorithms, such as severe expansion of configuration space, high complexity of motion con-ditions, and visual ambiguities among nearby targets, among which the visual ambiguity problem is the central challenge. In this paper, we address this problem by embedding adaptive mixture observation models (AMOM) into a mixture tracker which is implemented in Particle Filter framework. In AMOM, the extracted multiple features for appearance description are combined according to their discriminative power between ambiguity prone objects, where the discriminability of features are evaluated by online entropy-based feature selection techniques. The induction of AMOM can help to surmount the Incapa-bility of conventional mixture tracker in handling object occlusions, and meanwhile retain its merits of flexibility and high efficiency. The final experiments show significant improvement in MOT scenarios compared with other methods.

  9. Design and modeling of small scale multiple fracturing experiments

    Energy Technology Data Exchange (ETDEWEB)

    Cuderman, J F

    1981-12-01

    Recent experiments at the Nevada Test Site (NTS) have demonstrated the existence of three distinct fracture regimes. Depending on the pressure rise time in a borehole, one can obtain hydraulic, multiple, or explosive fracturing behavior. The use of propellants rather than explosives in tamped boreholes permits tailoring of the pressure risetime over a wide range since propellants having a wide range of burn rates are available. This technique of using the combustion gases from a full bore propellant charge to produce controlled borehole pressurization is termed High Energy Gas Fracturing (HEGF). Several series of HEGF, in 0.15 m and 0.2 m diameter boreholes at 12 m depths, have been completed in a tunnel complex at NTS where mineback permitted direct observation of fracturing obtained. Because such large experiments are costly and time consuming, smaller scale experiments are desirable, provided results from small experiments can be used to predict fracture behavior in larger boreholes. In order to design small scale gas fracture experiments, the available data from previous HEGF experiments were carefully reviewed, analytical elastic wave modeling was initiated, and semi-empirical modeling was conducted which combined predictions for statically pressurized boreholes with experimental data. The results of these efforts include (1) the definition of what constitutes small scale experiments for emplacement in a tunnel complex at the Nevada Test Site, (2) prediction of average crack radius, in ash fall tuff, as a function of borehole size and energy input per unit length, (3) definition of multiple-hydraulic and multiple-explosive fracture boundaries as a function of boreholes size and surface wave velocity, (4) semi-empirical criteria for estimating stress and acceleration, and (5) a proposal that multiple fracture orientations may be governed by in situ stresses.

  10. Modeling of a Multiple Digital Automatic Gain Control System

    Institute of Scientific and Technical Information of China (English)

    WANG Jingdian; LU Xiuhong; ZHANG Li

    2008-01-01

    Automatic gain control (AGC) has been used in many applications. The key features of AGC, including a steady state output and static/dynamic timing response, depend mainly on key parameters such as the reference and the filter coefficients. A simple model developed to describe AGC systems based on several simple assumptions shows that AGC always converges to the reference and that the timing constant depends on the filter coefficients. Measures are given to prevent oscillations and limit cycle effects. The simple AGC system is adapted to a multiple AGC system for a TV tuner in a much more efficient model. Simulations using the C language are 16 times faster than those with MATLAB, and 10 times faster than those with a mixed register transfer level (RTL)-simulation program with integrated circuit emphasis (SPICE) model.

  11. Multiple sclerosis animal models: a clinical and histopathological perspective.

    Science.gov (United States)

    Kipp, Markus; Nyamoya, Stella; Hochstrasser, Tanja; Amor, Sandra

    2017-03-01

    There is a broad consensus that multiple sclerosis (MS) represents more than an inflammatory disease: it harbors several characteristic aspects of a classical neurodegenerative disorder, that is, damage to axons, synapses and nerve cell bodies. While we are equipped with appropriate therapeutic options to prevent immune-cell driven relapses, effective therapeutic options to prevent the progressing neurodegeneration are still missing. In this review article, we will discuss to what extent pathology of the progressive disease stage can be modeled in MS animal models. While acute and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), which are T cell dependent, are aptly suited to model relapsing-remitting phases of MS, other EAE models, especially the secondary progressive EAE stage in Biozzi ABH mice is better representing the secondary progressive phase of MS, which is refractory to many immune therapies. Besides EAE, the cuprizone model is rapidly gaining popularity to study the formation and progression of demyelinating CNS lesions without T cell involvement. Here, we discuss these two non-popular MS models. It is our aim to point out the pathological hallmarks of MS, and discuss which pathological aspects of the disease can be best studied in the various animal models available.

  12. Multiple Model-Based Robot Control: Development and Initial Evaluation

    Science.gov (United States)

    1988-12-01

    the control systems must be as precise as possible to ac- count for high speed robot dynamics . Previous research has shown that payload adaptation is...model for robot dynamics is adequate, and that the coefficients of the model are estimated on-line DD79,Ser87,LE97,KG83]. The adaptive per- turbation...eigenvalues of F(a, t) revealed that linearized robot dynamics was a function of the trajectory and had a weak dependence on payload. The slight F(a

  13. Trust Evaluation Model based on Multiple Service Attributes

    Directory of Open Access Journals (Sweden)

    Xiaoxue Ma

    2011-06-01

    Full Text Available when the most trusted models evaluate level of trust about service entities at present, the credibility of the service attributes whether the two sides trading result is credible is rather ambiguous, which makes the evaluation model lack of persuasion, and not very good depict the complexity and uncertainty of trust relationship between the two sides. In view of the above questions, learning trust relationship from human society, according to the service of the node itself, abstracting representative multiple service attributes from the trusted relationship of the node service, service requester comprehensive evaluates multiple service attributes provided by service provider based on personal interest, and combines with the trust value, decide whether to trade finally; after the transaction, service request calculates QoS(quality of service difference degree according to actual QoS and service provider’own QoS claimed to judge the credibility of service provider, then gives corresponding rewards and punishment and trust update. Simulation results show that the model can evaluative accurately the node’s trust degree and effectively control of malicious nodes attack, when the malicious nodes have a higher proportion in the system ,it can still keep high success rate.

  14. Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions

    KAUST Repository

    Najibi, Seyed Morteza

    2017-02-08

    Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

  15. Modelling genetic susceptibility to multiple sclerosis with family data.

    Science.gov (United States)

    O'Gorman, Cullen; Lin, Rui; Stankovich, James; Broadley, Simon A

    2013-01-01

    A genetic contribution to susceptibility is well established in multiple sclerosis (MS) and 57 associated genetic loci have been identified. We have undertaken a meta-analysis of familial risk studies with the aims of providing definitive figures for risks to relatives, performing a segregation analysis and estimating the proportion of the overall genetic risk that currently identified genes represent. We have used standard methods of meta-analysis combined with novel approaches to age adjustment to provide directly comparable estimates of lifetime risk. The overall recurrence risk for monozygotic twins was 18.2% and for siblings 2.7%. The recurrence risk for dizygotic twins was significantly higher than for siblings. The overall estimate of sibling relative risk (λ(S)) was 16.8. Risks for older relatives (parents, siblings, aunts, uncles and cousins) show a latitudinal gradient, in line with population risk. No latitudinal gradient for λ(S) was seen. Segregation analysis supports a multiplicative model of one locus of moderate effect with many loci of small effect. The estimated contribution of the 57 known MS loci is 18-24% of λ(S). This meta-analysis supports the notion of MS being in part the result of multiple genetic susceptibility factors and environmental factors.

  16. Modelling the interplay of multiple cues in prosodic focus marking

    Directory of Open Access Journals (Sweden)

    Anja Arnhold

    2017-03-01

    Full Text Available Focus marking is an important function of prosody in many languages. While many phonological accounts concentrate on fundamental frequency (F0, studies have established several additional cues to information structure. However, the relationship between these cues is rarely investigated. We simultaneously analyzed five prosodic cues to focus—F0 range, word duration, intensity, voice quality, the location of the F0 maximum, and the occurrence of pauses—in a set of 947 simple Subject Verb Object (SVO sentences uttered by 17 native speakers of Finnish. Using random forest and generalized additive mixed modelling, we investigated the systematicity of prosodic focus marking, the importance of each cue as a predictor, and their functional shape. Results indicated a highly consistent differentiation between narrow focus and givenness, marked by at least F0 range, word duration, intensity, and the location of the F0 maximum, with F0 range being the most important predictor. No cue had a linear relationship with focus condition. To account for the simultaneous significance of several predictors, we argue that these findings support treating multiple prosodic cues to focus in Finnish as correlates of prosodic phrasing. Thus, we suggest that prosodic phrasing, having multiple functions, is also marked with multiple cues to enhance communicative efficiency.

  17. In vitro and in vivo models of multiple sclerosis.

    Science.gov (United States)

    van der Star, Baukje J; Vogel, Daphne Y S; Kipp, Markus; Puentes, Fabiola; Baker, David; Amor, Sandra

    2012-08-01

    Multiple sclerosis (MS) is widely considered to be the result of an aggressive autoreactive T cell attack on myelin. How these autoimmune responses arise in MS is unclear, but they could result from virus infections. Thus, viral and autoimmune diseases in animals have been used to investigate the possible pathogenic mechanisms operating in MS. The autoimmune model, experimental autoimmune encephalomyelitis, is the most widely-used animal model and has greatly influenced therapeutic approaches targeting autoimmune responses. To investigate demyelination and remyelination in the absence of the adaptive immune response, toxin-induced demyelination models are used. These include using cuprizone, ethidium bromide and lysolecithin to induce myelin damage, which rapidly lead to remyelination when the toxins are withdrawn. The virus models include natural and experimental infections such as canine distemper, visna infection of sheep, and infection of non-human primates. The most commonly used viral models in rodents are Semliki Forest virus and Theiler's murine encephalomyelitis virus. The viral and experimental autoimmune encephalomyelitis models have been instrumental in the understanding of how viruses trigger inflammation, demyelination and neurodegeneration in the central nervous system. However, due to complexity of the animal models, pathological mechanisms are also examined in central nervous system cell culture systems including co-cultures, aggregate cultures and brain slice cultures. Here we critically review in vitro and in vivo models used to investigate MS. Since knowledge gained from these models forms the basis for the development of new therapeutic approaches for MS, we address the applicability of the models. Finally, we provide guidance for using and reporting animal studies with the aim of improving translational studies to the clinic.

  18. Generalized multiplicative error models: Asymptotic inference and empirical analysis

    Science.gov (United States)

    Li, Qian

    This dissertation consists of two parts. The first part focuses on extended Multiplicative Error Models (MEM) that include two extreme cases for nonnegative series. These extreme cases are common phenomena in high-frequency financial time series. The Location MEM(p,q) model incorporates a location parameter so that the series are required to have positive lower bounds. The estimator for the location parameter turns out to be the minimum of all the observations and is shown to be consistent. The second case captures the nontrivial fraction of zero outcomes feature in a series and combines a so-called Zero-Augmented general F distribution with linear MEM(p,q). Under certain strict stationary and moment conditions, we establish a consistency and asymptotic normality of the semiparametric estimation for these two new models. The second part of this dissertation examines the differences and similarities between trades in the home market and trades in the foreign market of cross-listed stocks. We exploit the multiplicative framework to model trading duration, volume per trade and price volatility for Canadian shares that are cross-listed in the New York Stock Exchange (NYSE) and the Toronto Stock Exchange (TSX). We explore the clustering effect, interaction between trading variables, and the time needed for price equilibrium after a perturbation for each market. The clustering effect is studied through the use of univariate MEM(1,1) on each variable, while the interactions among duration, volume and price volatility are captured by a multivariate system of MEM(p,q). After estimating these models by a standard QMLE procedure, we exploit the Impulse Response function to compute the calendar time for a perturbation in these variables to be absorbed into price variance, and use common statistical tests to identify the difference between the two markets in each aspect. These differences are of considerable interest to traders, stock exchanges and policy makers.

  19. Multiplicative point process as a model of trading activity

    Science.gov (United States)

    Gontis, V.; Kaulakys, B.

    2004-11-01

    Signals consisting of a sequence of pulses show that inherent origin of the 1/ f noise is a Brownian fluctuation of the average interevent time between subsequent pulses of the pulse sequence. In this paper, we generalize the model of interevent time to reproduce a variety of self-affine time series exhibiting power spectral density S( f) scaling as a power of the frequency f. Furthermore, we analyze the relation between the power-law correlations and the origin of the power-law probability distribution of the signal intensity. We introduce a stochastic multiplicative model for the time intervals between point events and analyze the statistical properties of the signal analytically and numerically. Such model system exhibits power-law spectral density S( f)∼1/ fβ for various values of β, including β= {1}/{2}, 1 and {3}/{2}. Explicit expressions for the power spectra in the low-frequency limit and for the distribution density of the interevent time are obtained. The counting statistics of the events is analyzed analytically and numerically, as well. The specific interest of our analysis is related with the financial markets, where long-range correlations of price fluctuations largely depend on the number of transactions. We analyze the spectral density and counting statistics of the number of transactions. The model reproduces spectral properties of the real markets and explains the mechanism of power-law distribution of trading activity. The study provides evidence that the statistical properties of the financial markets are enclosed in the statistics of the time interval between trades. A multiplicative point process serves as a consistent model generating this statistics.

  20. Rank-based model selection for multiple ions quantum tomography

    Science.gov (United States)

    Guţă, Mădălin; Kypraios, Theodore; Dryden, Ian

    2012-10-01

    The statistical analysis of measurement data has become a key component of many quantum engineering experiments. As standard full state tomography becomes unfeasible for large dimensional quantum systems, one needs to exploit prior information and the ‘sparsity’ properties of the experimental state in order to reduce the dimensionality of the estimation problem. In this paper we propose model selection as a general principle for finding the simplest, or most parsimonious explanation of the data, by fitting different models and choosing the estimator with the best trade-off between likelihood fit and model complexity. We apply two well established model selection methods—the Akaike information criterion (AIC) and the Bayesian information criterion (BIC)—two models consisting of states of fixed rank and datasets such as are currently produced in multiple ions experiments. We test the performance of AIC and BIC on randomly chosen low rank states of four ions, and study the dependence of the selected rank with the number of measurement repetitions for one ion states. We then apply the methods to real data from a four ions experiment aimed at creating a Smolin state of rank 4. By applying the two methods together with the Pearson χ2 test we conclude that the data can be suitably described with a model whose rank is between 7 and 9. Additionally we find that the mean square error of the maximum likelihood estimator for pure states is close to that of the optimal over all possible measurements.

  1. The multilevel p2 model : A random effects model for the analysis of multiple social networks

    NARCIS (Netherlands)

    Zijlstra, B.J.H.; van Duijn, M.A.J.; Snijders, T.A.B.

    2006-01-01

    The p2 model is a random effects model with covariates for the analysis of binary directed social network data coming from a single observation of a social network. Here, a multilevel variant of the p2 model is proposed for the case of multiple observations of social networks, for example, in a samp

  2. REVEAL: An Extensible Reduced Order Model Builder for Simulation and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Khushbu; Sharma, Poorva; Ma, Jinliang; Lo, Chaomei; Gorton, Ian; Liu, Yan

    2013-04-30

    Many science domains need to build computationally efficient and accurate representations of high fidelity, computationally expensive simulations. These computationally efficient versions are known as reduced-order models. This paper presents the design and implementation of a novel reduced-order model (ROM) builder, the REVEAL toolset. This toolset generates ROMs based on science- and engineering-domain specific simulations executed on high performance computing (HPC) platforms. The toolset encompasses a range of sampling and regression methods that can be used to generate a ROM, automatically quantifies the ROM accuracy, and provides support for an iterative approach to improve ROM accuracy. REVEAL is designed to be extensible in order to utilize the core functionality with any simulator that has published input and output formats. It also defines programmatic interfaces to include new sampling and regression techniques so that users can ‘mix and match’ mathematical techniques to best suit the characteristics of their model. In this paper, we describe the architecture of REVEAL and demonstrate its usage with a computational fluid dynamics model used in carbon capture.

  3. Multiple Local Reconstruction Model-based Fault Diagnosis for Continuous Processes

    Institute of Scientific and Technical Information of China (English)

    ZHAO Chun-Hui; LI Wen-Qing; SUN You-Xian; GAO Fu-Rong

    2013-01-01

    In the present work,the multiplicity of fault characteristics is proposed and analyzed to improve the fault diagnosis performance.It is based on the following recognition that the underlying fault characteristics in general do not stay constant but will present changes along the time direction.That is,the fault process reveals different variable correlations across different time periods.To analyze the multiplicity of fault characteristics,a fault division algorithm is developed to divide the fault process into multiple local time periods where the fault characteristics are deemed similar within the same local time period.Then a representative fault decomposition model is built in each local time period to reveal the relationships between the fault and normal operation status.In this way,these different fault characteristics can be modeled respectively.The proposed method gives an interesting insight into the fault evolvement behaviors and a more accurate from-fault-to-normal reconstruction result can be expected for fault diagnosis.The feasibility and performance of the proposed fault diagnosis method are illustrated with the Tennessee Eastman process.

  4. Linear Modeling of Multiple Sclerosis and Its Subgroubs

    Directory of Open Access Journals (Sweden)

    Yeliz Karaca

    2015-03-01

    Full Text Available OBJECTIVE: In this study,120 patients diagnosed with clinical multiple sclerosis (MS of relapsing remitting type (RRMS, secondary progressive type (SPMS and primary progressive type (PPMS were examined, as well as 19 healthy subjects. All subjects were between the ages of 20 and 55. Disability levels of MS symptoms were determined using Expanded Disability Status Scale (EDSS. We focused on three regions in the brain, brain stem, periventricular corpus callosum, and upper cervical regions EDSS scores and number of lesions in these three regions are considered as the parameters of the linear mathematical model to determine the subgroups of the disease. METHODS: Initially, the distinction between healthy subjects and patients was made. Then, if the subject was determined to have MS, the distinction of type, i.e. RRMS, SPMS/PPMS, and later, RRMS/SPMS distinction was made. In all determinations linear models were used and number of lesions in the specified three regions and EDSS scores were assumed as the parameters of the model. The coefficients of the models were obtained by least squares method. RESULTS: In the linear model attached to MR parameters, there was 100% success for distinction of patients and healthy subjects. Success for distinction of RRMS and SPMS/PPMS patients and RRMS/SPMS patients was 94% and 78.94%, respectively is attained. Based on EDSS scores, linear model provides 99% success in the distinction between patients and healthy subjects. In the models created for the distinction between groups, success rate was 94% was for RRMS-SPMS/PPMS and 64% for RRMS/SPMS. CONCLUSION: The correlation of MS diagnosis using various features obtained from MR images and EDSS scores with subgroups of the disease and the possibility of developing a linear model were determined. Using the features having the highest correlation rate, various linear models were developed and high success was achieved.

  5. Social conflict exacerbates an animal model of multiple sclerosis.

    Science.gov (United States)

    Meagher, Mary W; Johnson, Robin R; Vichaya, Elisabeth Good; Young, Erin E; Lunt, Shannon; Welsh, C Jane

    2007-07-01

    A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.

  6. Finite element modelling of internal and multiple localized cracks

    Science.gov (United States)

    Saloustros, Savvas; Pelà, Luca; Cervera, Miguel; Roca, Pere

    2017-02-01

    Tracking algorithms constitute an efficient numerical technique for modelling fracture in quasi-brittle materials. They succeed in representing localized cracks in the numerical model without mesh-induced directional bias. Currently available tracking algorithms have an important limitation: cracking originates either from the boundary of the discretized domain or from predefined "crack-root" elements and then propagates along one orientation. This paper aims to circumvent this drawback by proposing a novel tracking algorithm that can simulate cracking starting at any point of the mesh and propagating along one or two orientations. This enhancement allows the simulation of structural case-studies experiencing multiple cracking. The proposed approach is validated through the simulation of a benchmark example and an experimentally tested structural frame under in-plane loading. Mesh-bias independency of the numerical solution, computational cost and predicted collapse mechanisms with and without the tracking algorithm are discussed.

  7. Modelling and validation of multiple reflections for enhanced laser welding

    Science.gov (United States)

    Milewski, J.; Sklar, E.

    1996-05-01

    The effects of multiple internal reflections within a laser weld joint as functions of joint geometry and processing conditions have been characterized. A computer-based ray tracing model is used to predict the reflective propagation of laser beam energy focused into the narrow gap of a metal joint for the purpose of predicting the location of melting and coalescence to form a weld. Quantitative comparisons are made between simulation cases. Experimental results are provided for qualitative model validation. This method is proposed as a way to enhance process efficiency and design laser welds which display deep penetration and high depth-to-width aspect ratios without high powered systems or keyhole mode melting.

  8. Research and application of hierarchical model for multiple fault diagnosis

    Institute of Scientific and Technical Information of China (English)

    An Ruoming; Jiang Xingwei; Song Zhengji

    2005-01-01

    Computational complexity of complex system multiple fault diagnosis is a puzzle at all times. Based on the well-known Mozetic's approach, a novel hierarchical model-based diagnosis methodology is put forward for improving efficiency of multi-fault recognition and localization. Structural abstraction and weighted fault propagation graphs are combined to build diagnosis model. The graphs have weighted arcs with fault propagation probabilities and propagation strength. For solving the problem of coupled faults, two diagnosis strategies are used: one is the Lagrangian relaxation and the primal heuristic algorithms; another is the method of propagation strength. Finally, an applied example shows the applicability of the approach and experimental results are given to show the superiority of the presented technique.

  9. A Hybrid Multiple Criteria Decision Making Model for Supplier Selection

    Directory of Open Access Journals (Sweden)

    Chung-Min Wu

    2013-01-01

    Full Text Available The sustainable supplier selection would be the vital part in the management of a sustainable supply chain. In this study, a hybrid multiple criteria decision making (MCDM model is applied to select optimal supplier. The fuzzy Delphi method, which can lead to better criteria selection, is used to modify criteria. Considering the interdependence among the selection criteria, analytic network process (ANP is then used to obtain their weights. To avoid calculation and additional pairwise comparisons of ANP, a technique for order preference by similarity to ideal solution (TOPSIS is used to rank the alternatives. The use of a combination of the fuzzy Delphi method, ANP, and TOPSIS, proposing an MCDM model for supplier selection, and applying these to a real case are the unique features of this study.

  10. Multiple Scattering Model for Optical Coherence Tomography with Rytov Approximation

    KAUST Repository

    Li, Muxingzi

    2017-04-24

    Optical Coherence Tomography (OCT) is a coherence-gated, micrometer-resolution imaging technique that focuses a broadband near-infrared laser beam to penetrate into optical scattering media, e.g. biological tissues. The OCT resolution is split into two parts, with the axial resolution defined by half the coherence length, and the depth-dependent lateral resolution determined by the beam geometry, which is well described by a Gaussian beam model. The depth dependence of lateral resolution directly results in the defocusing effect outside the confocal region and restricts current OCT probes to small numerical aperture (NA) at the expense of lateral resolution near the focus. Another limitation on OCT development is the presence of a mixture of speckles due to multiple scatterers within the coherence length, and other random noise. Motivated by the above two challenges, a multiple scattering model based on Rytov approximation and Gaussian beam optics is proposed for the OCT setup. Some previous papers have adopted the first Born approximation with the assumption of small perturbation of the incident field in inhomogeneous media. The Rytov method of the same order with smooth phase perturbation assumption benefits from a wider spatial range of validity. A deconvolution method for solving the inverse problem associated with the first Rytov approximation is developed, significantly reducing the defocusing effect through depth and therefore extending the feasible range of NA.

  11. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  12. Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Sathitruangsak, Chirawadee; Righolt, Christiaan H; Klewes, Ludger; Tammur, Pille; Ilus, Tiiu; Tamm, Anu; Punab, Mari; Olujohungbe, Adebayo; Mai, Sabine

    2015-05-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM. © 2014 Wiley Periodicals, Inc.

  13. The multiple process model of goal-directed reaching revisited.

    Science.gov (United States)

    Elliott, Digby; Lyons, James; Hayes, Spencer J; Burkitt, James J; Roberts, James W; Grierson, Lawrence E M; Hansen, Steve; Bennett, Simon J

    2017-01-01

    Recently our group forwarded a model of speed-accuracy relations in goal-directed reaching. A fundamental feature of our multiple process model was the distinction between two types of online regulation: impulse control and limb-target control. Impulse control begins during the initial stages of the movement trajectory and involves a comparison of actual limb velocity and direction to an internal representation of expectations about the limb trajectory. Limb-target control involves discrete error-reduction based on the relative positions of the limb and the target late in the movement. Our model also considers the role of eye movements, practice, energy optimization and strategic behavior in limb control. Here, we review recent work conducted to test specific aspects of our model. As well, we consider research not fully incorporated into our earlier contribution. We conclude that a slightly modified and expanded version of our model, that includes crosstalk between the two forms of online regulation, does an excellent job of explaining speed, accuracy, and energy optimization in goal-directed reaching.

  14. Evolution: Ocean Models Reveal Life in Deep Seas.

    Science.gov (United States)

    Eizaguirre, Christophe

    2016-09-26

    Even though the deep sea represents the largest area in the world, evolution of species from those environments remains largely unstudied. A series of recent papers indicate that combining molecular tools with biophysical models can help us resolve some of these deep mysteries.

  15. Mechanistic species distribution modeling reveals a niche shift during invasion.

    Science.gov (United States)

    Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

    2017-06-01

    Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

  16. Mindfulness facets, trait emotional intelligence, emotional distress, and multiple health behaviors: A serial two-mediator model.

    Science.gov (United States)

    Jacobs, Ingo; Wollny, Anna; Sim, Chu-Won; Horsch, Antje

    2016-06-01

    In the present study, we tested a serial mindfulness facets-trait emotional intelligence (TEI)-emotional distress-multiple health behaviors mediation model in a sample of N = 427 German-speaking occupational therapists. The mindfulness facets-TEI-emotional distress section of the mediation model revealed partial mediation for the mindfulness facets Act with awareness (Act/Aware) and Accept without judgment (Accept); inconsistent mediation was found for the Describe facet. The serial two-mediator model included three mediational pathways that may link each of the four mindfulness facets with multiple health behaviors. Eight out of 12 indirect effects reached significance and fully mediated the links between Act/Aware and Describe to multiple health behaviors; partial mediation was found for Accept. The mindfulness facet Observe was most relevant for multiple health behaviors, but its relation was not amenable to mediation. Implications of the findings will be discussed.

  17. Comparison of Geant4 multiple Coulomb scattering models with theory for radiotherapy protons

    CERN Document Server

    Makarova, Anastasia; Sauerwein, Wolfgang

    2016-01-01

    Usually, Monte Carlo models are validated against experimental data. However, models of multiple Coulomb scattering (MCS) in the Gaussian approximation are exceptional in that we have theories which are probably more accurate than the experiments which have, so far, been done to test them. In problems directly sensitive to the distribution of angles leaving the target, the relevant theory is the Moliere/Fano/Hanson variant of Moliere theory. For transverse spreading of the beam in the target itself, the theory of Preston and Koehler holds. Therefore, in this paper we compare Geant4 simulations, using the Urban and Wentzel models of MCS, with theory rather than experiment, revealing trends which would otherwise be obscured by experimental scatter. For medium-energy (radiotherapy) protons, and low-Z (water-like) target materials, Wentzel appears to be better than Urban in simulating the distribution of outgoing angles. For beam spreading in the target itself, the two models are essentially equal.

  18. Modeling multiple resource limitation in tropical dry forests

    Science.gov (United States)

    Medvigy, D.; Xu, X.; Zarakas, C.

    2015-12-01

    Tropical dry forests (TDFs) are characterized by a long dry season when little rain falls. At the same time, many neotropical soils are highly weathered and relatively nutrient poor. Because TDFs are often subject to both water and nutrient constraints, the question of how they will respond to environmental perturbations is both complex and highly interesting. Models, our basic tools for projecting ecosystem responses to global change, can be used to address this question. However, few models have been specifically parameterized for TDFs. Here, we present a new version of the Ecosystem Demography 2 (ED2) model that includes a new parameterization of TDFs. In particular, we focus on the model's framework for representing limitation by multiple resources (carbon, water, nitrogen, and phosphorus). Plant functional types are represented in terms of a dichotomy between "acquisitive" and "conservative" resource acquisition strategies. Depending on their resource acquisition strategy and basic stoichiometry, plants can dynamically adjust their allocation to organs (leaves, stem, roots), symbionts (e.g. N2-fixing bacteria), and mycorrhizal fungi. Several case studies are used to investigate how resource acquisition strategies affect ecosystem responses to environmental perturbations. Results are described in terms of the basic setting (e.g., rich vs. poor soils; longer vs. shorter dry season), and well as the type and magnitude of environmental perturbation (e.g., changes in precipitation or temperature; changes in nitrogen deposition). Implications for ecosystem structure and functioning are discussed.

  19. Modeling healthcare data using multiple-channel latent Dirichlet allocation.

    Science.gov (United States)

    Lu, Hsin-Min; Wei, Chih-Ping; Hsiao, Fei-Yuan

    2016-04-01

    Information and communications technologies have enabled healthcare institutions to accumulate large amounts of healthcare data that include diagnoses, medications, and additional contextual information such as patient demographics. To gain a better understanding of big healthcare data and to develop better data-driven clinical decision support systems, we propose a novel multiple-channel latent Dirichlet allocation (MCLDA) approach for modeling diagnoses, medications, and contextual information in healthcare data. The proposed MCLDA model assumes that a latent health status group structure is responsible for the observed co-occurrences among diagnoses, medications, and contextual information. Using a real-world research testbed that includes one million healthcare insurance claim records, we investigate the utility of MCLDA. Our empirical evaluation results suggest that MCLDA is capable of capturing the comorbidity structures and linking them with the distribution of medications. Moreover, MCLDA is able to identify the pairing between diagnoses and medications in a record based on the assigned latent groups. MCLDA can also be employed to predict missing medications or diagnoses given partial records. Our evaluation results also show that, in most cases, MCLDA outperforms alternative methods such as logistic regressions and the k-nearest-neighbor (KNN) model for two prediction tasks, i.e., medication and diagnosis prediction. Thus, MCLDA represents a promising approach to modeling healthcare data for clinical decision support.

  20. Direction of Effects in Multiple Linear Regression Models.

    Science.gov (United States)

    Wiedermann, Wolfgang; von Eye, Alexander

    2015-01-01

    Previous studies analyzed asymmetric properties of the Pearson correlation coefficient using higher than second order moments. These asymmetric properties can be used to determine the direction of dependence in a linear regression setting (i.e., establish which of two variables is more likely to be on the outcome side) within the framework of cross-sectional observational data. Extant approaches are restricted to the bivariate regression case. The present contribution extends the direction of dependence methodology to a multiple linear regression setting by analyzing distributional properties of residuals of competing multiple regression models. It is shown that, under certain conditions, the third central moments of estimated regression residuals can be used to decide upon direction of effects. In addition, three different approaches for statistical inference are discussed: a combined D'Agostino normality test, a skewness difference test, and a bootstrap difference test. Type I error and power of the procedures are assessed using Monte Carlo simulations, and an empirical example is provided for illustrative purposes. In the discussion, issues concerning the quality of psychological data, possible extensions of the proposed methods to the fourth central moment of regression residuals, and potential applications are addressed.

  1. Investigating multiple solutions in the constrained minimal supersymmetric standard model

    Energy Technology Data Exchange (ETDEWEB)

    Allanach, B.C. [DAMTP, CMS, University of Cambridge,Wilberforce Road, Cambridge, CB3 0HA (United Kingdom); George, Damien P. [DAMTP, CMS, University of Cambridge,Wilberforce Road, Cambridge, CB3 0HA (United Kingdom); Cavendish Laboratory, University of Cambridge,JJ Thomson Avenue, Cambridge, CB3 0HE (United Kingdom); Nachman, Benjamin [SLAC, Stanford University,2575 Sand Hill Rd, Menlo Park, CA 94025 (United States)

    2014-02-07

    Recent work has shown that the Constrained Minimal Supersymmetric Standard Model (CMSSM) can possess several distinct solutions for certain values of its parameters. The extra solutions were not previously found by public supersymmetric spectrum generators because fixed point iteration (the algorithm used by the generators) is unstable in the neighbourhood of these solutions. The existence of the additional solutions calls into question the robustness of exclusion limits derived from collider experiments and cosmological observations upon the CMSSM, because limits were only placed on one of the solutions. Here, we map the CMSSM by exploring its multi-dimensional parameter space using the shooting method, which is not subject to the stability issues which can plague fixed point iteration. We are able to find multiple solutions where in all previous literature only one was found. The multiple solutions are of two distinct classes. One class, close to the border of bad electroweak symmetry breaking, is disfavoured by LEP2 searches for neutralinos and charginos. The other class has sparticles that are heavy enough to evade the LEP2 bounds. Chargino masses may differ by up to around 10% between the different solutions, whereas other sparticle masses differ at the sub-percent level. The prediction for the dark matter relic density can vary by a hundred percent or more between the different solutions, so analyses employing the dark matter constraint are incomplete without their inclusion.

  2. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia

    Science.gov (United States)

    Kerr, Peter J.; Cattadori, Isabella M.; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G.; Boag, Brian; Ghedin, Elodie

    2017-01-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954–1955) and between 2008–2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms. PMID:28253375

  3. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

    Science.gov (United States)

    Kerr, Peter J; Cattadori, Isabella M; Rogers, Matthew B; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G; Boag, Brian; Eden, John-Sebastian; Ghedin, Elodie; Read, Andrew F; Holmes, Edward C

    2017-03-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955) and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

  4. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

    Directory of Open Access Journals (Sweden)

    Peter J Kerr

    2017-03-01

    Full Text Available The co-evolution of myxoma virus (MYXV and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955 and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release Lausanne strain. Inferred virulence ranged from highly virulent (grade 1 to highly attenuated (grade 5. Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

  5. Multiple kinship in two Spanish regions: new model relating multiple and simple consanguinity.

    Science.gov (United States)

    Calderón, R; Peña, J A; Delgado, J; Morales, B

    1998-06-01

    The structure of the different categories of multiple consanguineous marriages (MCMs) and their historical variation patterns are analyzed in the Spanish dioceses of Alava (Basque Country) and Sigüenza-Guadalajara (Castile). Consanguineous marriages, up to third cousins, were taken from ecclesiastical dispensations, and the periods studied were 1831-1980 for Alava and 1861-1980 for Sigüenza-Guadalajara. Significant differences exist in the MCM rates in the two Spanish areas. In this study a model is proposed to prove that in a general population there may be dependence between MCM rates for specific relationships and the frequencies of those types of relationships in the form of simple consanguineous marriages (SCMs). The effects of avoidance and preferentiality and of underreporting are discussed to explain the deviations between observed and expected consanguineous marriage frequencies. A limit to the weight of remote consanguinity on the population inbreeding coefficient F is determined. The relationship between FT/FS and ms values from our two Spanish populations are fitted to curvilinear regressions. FT is the total population inbreeding coefficient, FS is the contribution to FT from SCMs, and ms is the relative observed frequency of SCMs in the general population.

  6. Species delimitation in lemurs: multiple genetic loci reveal low levels of species diversity in the genus Cheirogaleus

    Directory of Open Access Journals (Sweden)

    Rasoloarison Rodin M

    2009-02-01

    Full Text Available Abstract Background Species are viewed as the fundamental unit in most subdisciplines of biology. To conservationists this unit represents the currency for global biodiversity assessments. Even though Madagascar belongs to one of the top eight biodiversity hotspots of the world, the taxonomy of its charismatic lemuriform primates is not stable. Within the last 25 years, the number of described lemur species has more than doubled, with many newly described species identified among the nocturnal and small-bodied cheirogaleids. Here, we characterize the diversity of the dwarf lemurs (genus Cheirogaleus and assess the status of the seven described species, based on phylogenetic and population genetic analysis of mtDNA (cytb + cox2 and three nuclear markers (adora3, fiba and vWF. Results This study identified three distinct evolutionary lineages within the genus Cheirogaleus. Population genetic cluster analyses revealed a further layer of population divergence with six distinct genotypic clusters. Conclusion Based on the general metapopulation lineage concept and multiple concordant data sets, we identify three exclusive groups of dwarf lemur populations that correspond to three of the seven named species: C. major, C. medius and C. crossleyi. These three species were found to be genealogically exclusive in both mtDNA and nDNA loci and are morphologically distinguishable. The molecular and morphometric data indicate that C. adipicaudatus and C. ravus are synonymous with C. medius and C. major, respectively. Cheirogaleus sibreei falls into the C. medius mtDNA clade, but in morphological analyses the membership is not clearly resolved. We do not have sufficient data to assess the status of C. minusculus. Although additional patterns of population differentiation are evident, there are no clear subdivisions that would warrant additional specific status. We propose that ecological and more geographic data should be collected to confirm these results.

  7. Physiological Stress Responses in Amphibian Larvae to Multiple Stressors Reveal Marked Anthropogenic Effects even below Lethal Levels.

    Science.gov (United States)

    Burraco, Pablo; Gomez-Mestre, Ivan

    Natural and anthropogenic disturbances cause profound alterations in organisms, inducing physiological adjustments to avoid, reduce, or remedy the impact of disturbances. In vertebrates, the stress response is regulated via neuroendocrine pathways, including the hypothalamic-pituitary-interrenal axis that regulates the secretion of glucocorticoids. Glucocorticoids have cascading effects on multiple physiological pathways, affecting the metabolic rate, reactive oxygen species production, or immune system. Determining the extent to which natural and anthropogenic environmental factors induce stress responses in vertebrates is of great importance in ecology and conservation biology. Here we study the physiological stress response in spadefoot toad tadpoles (Pelobates cultripes) against three levels of a series of natural and anthropogenic stressors common to many aquatic systems: salinity (0, 6, and 9 ppt), herbicide (0, 1, and 2 mg/L acid equivalent of glyphosate), water acidity (pH 4.5, 7.0, and 9.5), predators (absent, native, and invasive), and temperature (21°, 25°, and 29°C). The physiological stress response was assessed examining corticosterone levels, standard metabolic rate, activity of antioxidant enzymes, oxidative cellular damage in lipids, and immunological status. We found that common stressors substantially altered the physiological state of tadpoles. In particular, salinity and herbicides cause dramatic physiological changes in tadpoles. Moreover, tadpoles reduced corticosterone levels in the presence of natural predators but did not do so against invasive predators, indicating a lack of innate recognition. Corticosterone and the antioxidant enzyme glutathione reductase were the most sensitive parameters to stress in this study. Anthropogenic perturbations of aquatic systems pose serious threats to larval amphibians even at nonlethal concentrations, judging from the marked physiological stress responses generated, and reveal the importance of

  8. Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of fungus farming during periods of global warming

    Directory of Open Access Journals (Sweden)

    Jordal Bjarte H

    2012-08-01

    Full Text Available Abstract Background Fungus farming is an unusual life style in insects that has evolved many times in the wood boring weevils named ‘ambrosia beetles’. Multiple occurrences of this behaviour allow for a detailed comparison of the different origins of fungus farming through time, its directionality, and possible ancestral states. We tested these hypotheses with a phylogeny representing the largest data set to date, nearly 4 kb of nucleotides from COI, EF-1α, CAD, ArgK, 28S, and 200 scolytine taxa. Results Phylogenetic analyses using Bayesian or parsimony approaches placed the root of Scolytinae close to the tribe Scolytini and Microborus, but otherwise indicated low resolution at older nodes. More recent clades were well resolved, including ten origins of fungus farming. There were no subsequent reversals to bark or phloem feeding in the fungus farming clades. The oldest origin of fungus farming was estimated near 50 Ma, long after the origin of Scolytinae (100-120 Ma. Younger origins included the species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of independence between traits indicated that neither gregarious larval feeding nor regular inbreeding by sibling mating was strongly correlated with the origin of fungus farming. Conclusion Origins of fungus farming corresponded mainly with two periods of global warming in the Cenozoic era, which were characterised by broadly distributed tropical forests. Hence, it seems likely that warm climates and expanding tropical angiosperm forests played critical roles in the successful radiation of diverse fungus farming groups. However, further investigation will likely reveal additional biological factors that promote fungus farming.

  9. The intergenerational multiple deficit model and the case of dyslexia

    Directory of Open Access Journals (Sweden)

    Elsje evan Bergen

    2014-06-01

    Full Text Available Which children go on to develop dyslexia? Since dyslexia has a multifactorial aetiology, this question can be restated as: What are the factors that put children at high risk for developing dyslexia? It is argued that a useful theoretical framework to address this question is Pennington’s (2006 multiple deficit model (MDM. This model replaces models that attribute dyslexia to a single underlying cause. Subsequently, the generalist genes hypothesis for learning (disabilities (Plomin & Kovas, 2005 is described and integrated with the MDM. Finally, findings are presented from a longitudinal study with children at family risk for dyslexia. Such studies can contribute to testing and specifying the MDM. In this study, risk factors at both the child and family level were investigated. This led to the proposed intergenerational MDM, in which both parents confer liability via intertwined genetic and environmental pathways. Future scientific directions are discussed to investigate parent-offspring resemblance and transmission patterns, which will shed new light on disorder aetiology.

  10. The intergenerational multiple deficit model and the case of dyslexia

    Science.gov (United States)

    van Bergen, Elsje; van der Leij, Aryan; de Jong, Peter F.

    2014-01-01

    Which children go on to develop dyslexia? Since dyslexia has a multifactorial etiology, this question can be restated as: what are the factors that put children at high risk for developing dyslexia? It is argued that a useful theoretical framework to address this question is Pennington’s (2006) multiple deficit model (MDM). This model replaces models that attribute dyslexia to a single underlying cause. Subsequently, the generalist genes hypothesis for learning (dis)abilities (Plomin and Kovas, 2005) is described and integrated with the MDM. Next, findings are presented from a longitudinal study with children at family risk for dyslexia. Such studies can contribute to testing and specifying the MDM. In this study, risk factors at both the child and family level were investigated. This led to the proposed intergenerational MDM, in which both parents confer liability via intertwined genetic and environmental pathways. Future scientific directions are discussed to investigate parent-offspring resemblance and transmission patterns, which will shed new light on disorder etiology. PMID:24920944

  11. Modeling Pan Evaporation for Kuwait by Multiple Linear Regression

    Directory of Open Access Journals (Sweden)

    Jaber Almedeij

    2012-01-01

    Full Text Available Evaporation is an important parameter for many projects related to hydrology and water resources systems. This paper constitutes the first study conducted in Kuwait to obtain empirical relations for the estimation of daily and monthly pan evaporation as functions of available meteorological data of temperature, relative humidity, and wind speed. The data used here for the modeling are daily measurements of substantial continuity coverage, within a period of 17 years between January 1993 and December 2009, which can be considered representative of the desert climate of the urban zone of the country. Multiple linear regression technique is used with a procedure of variable selection for fitting the best model forms. The correlations of evaporation with temperature and relative humidity are also transformed in order to linearize the existing curvilinear patterns of the data by using power and exponential functions, respectively. The evaporation models suggested with the best variable combinations were shown to produce results that are in a reasonable agreement with observation values.

  12. Multiple-relaxation-time lattice Boltzmann kinetic model for combustion.

    Science.gov (United States)

    Xu, Aiguo; Lin, Chuandong; Zhang, Guangcai; Li, Yingjun

    2015-04-01

    To probe both the hydrodynamic nonequilibrium (HNE) and thermodynamic nonequilibrium (TNE) in the combustion process, a two-dimensional multiple-relaxation-time (MRT) version of lattice Boltzmann kinetic model (LBKM) for combustion phenomena is presented. The chemical energy released in the progress of combustion is dynamically coupled into the system by adding a chemical term to the LB kinetic equation. Aside from describing the evolutions of the conserved quantities, the density, momentum, and energy, which are what the Navier-Stokes model describes, the MRT-LBKM presents also a coarse-grained description on the evolutions of some nonconserved quantities. The current model works for both subsonic and supersonic flows with or without chemical reaction. In this model, both the specific-heat ratio and the Prandtl number are flexible, the TNE effects are naturally presented in each simulation step. The model is verified and validated via well-known benchmark tests. As an initial application, various nonequilibrium behaviors, including the complex interplays between various HNEs, between various TNEs, and between the HNE and TNE, around the detonation wave in the unsteady and steady one-dimensional detonation processes are preliminarily probed. It is found that the system viscosity (or heat conductivity) decreases the local TNE, but increases the global TNE around the detonation wave, that even locally, the system viscosity (or heat conductivity) results in two kinds of competing trends, to increase and to decrease the TNE effects. The physical reason is that the viscosity (or heat conductivity) takes part in both the thermodynamic and hydrodynamic responses.

  13. Decreasing Multicollinearity: A Method for Models with Multiplicative Functions.

    Science.gov (United States)

    Smith, Kent W.; Sasaki, M. S.

    1979-01-01

    A method is proposed for overcoming the problem of multicollinearity in multiple regression equations where multiplicative independent terms are entered. The method is not a ridge regression solution. (JKS)

  14. Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2015-10-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p < .0001). We offer proof that H. pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

  15. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modeling.

    Science.gov (United States)

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2014-11-10

    Following partial hepatectomy, the liver initiates a regenerative program involving hepatocyte priming and replication driven by coordinated cytokine and growth factor actions. We investigated the mechanisms underlying Adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn-/- mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn-/- mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to IL-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver. This article is protected by copyright. All rights reserved.

  16. Adiponectin fine-tuning of liver regeneration dynamics revealed through cellular network modelling.

    Science.gov (United States)

    Correnti, Jason M; Cook, Daniel; Aksamitiene, Edita; Swarup, Aditi; Ogunnaike, Babatunde; Vadigepalli, Rajanikanth; Hoek, Jan B

    2015-01-15

    Following partial hepatectomy, the liver initiates a regenerative programme involving hepatocyte priming and replication driven by the coordinated actions of cytokine and growth factors. We investigated the mechanisms underlying adiponectin's (Adn) regulation of liver regeneration through modulation of these mediators. Adn(-/-) mice showed delayed onset of hepatocyte replication, but accelerated cell cycle progression relative to wild-type mice, suggesting Adn has multiple effects fine-tuning the kinetics of liver regeneration. We developed a computational model describing the molecular and physiological kinetics of liver regeneration in Adn(-/-) mice. We employed this computational model to evaluate the underlying regulatory mechanisms. Our analysis predicted that Adn is required for an efficient early cytokine response to partial hepatectomy, but is inhibitory to later growth factor actions. Consistent with this prediction, Adn knockout reduced hepatocyte responses to interleukin-6 during the priming phase, but enhanced growth factor levels through peak hepatocyte replication. By contrast, supraphysiological concentrations of Adn resulting from rosiglitazone treatment suppressed regeneration by reducing growth factor levels during S phase, consistent with computational predictions. Together, these results revealed that Adn fine-tunes the progression of liver regeneration through dynamically modulating molecular mediator networks and cellular interactions within the liver.

  17. Cancer genomics object model: an object model for multiple functional genomics data for cancer research.

    Science.gov (United States)

    Park, Yu Rang; Lee, Hye Won; Cho, Sung Bum; Kim, Ju Han

    2007-01-01

    The development of functional genomics including transcriptomics, proteomics and metabolomics allow us to monitor a large number of key cellular pathways simultaneously. Several technology-specific data models have been introduced for the representation of functional genomics experimental data, including the MicroArray Gene Expression-Object Model (MAGE-OM), the Proteomics Experiment Data Repository (PEDRo), and the Tissue MicroArray-Object Model (TMA-OM). Despite the increasing number of cancer studies using multiple functional genomics technologies, there is still no integrated data model for multiple functional genomics experimental and clinical data. We propose an object-oriented data model for cancer genomics research, Cancer Genomics Object Model (CaGe-OM). We reference four data models: Functional Genomic-Object Model, MAGE-OM, TMAOM and PEDRo. The clinical and histopathological information models are created by analyzing cancer management workflow and referencing the College of American Pathology Cancer Protocols and National Cancer Institute Common Data Elements. The CaGe-OM provides a comprehensive data model for integrated storage and analysis of clinical and multiple functional genomics data.

  18. Shared mental models of integrated care: aligning multiple stakeholder perspectives.

    Science.gov (United States)

    Evans, Jenna M; Baker, G Ross

    2012-01-01

    Health service organizations and professionals are under increasing pressure to work together to deliver integrated patient care. A common understanding of integration strategies may facilitate the delivery of integrated care across inter-organizational and inter-professional boundaries. This paper aims to build a framework for exploring and potentially aligning multiple stakeholder perspectives of systems integration. The authors draw from the literature on shared mental models, strategic management and change, framing, stakeholder management, and systems theory to develop a new construct, Mental Models of Integrated Care (MMIC), which consists of three types of mental models, i.e. integration-task, system-role, and integration-belief. The MMIC construct encompasses many of the known barriers and enablers to integrating care while also providing a comprehensive, theory-based framework of psychological factors that may influence inter-organizational and inter-professional relations. While the existing literature on integration focuses on optimizing structures and processes, the MMIC construct emphasizes the convergence and divergence of stakeholders' knowledge and beliefs, and how these underlying cognitions influence interactions (or lack thereof) across the continuum of care. MMIC may help to: explain what differentiates effective from ineffective integration initiatives; determine system readiness to integrate; diagnose integration problems; and develop interventions for enhancing integrative processes and ultimately the delivery of integrated care. Global interest and ongoing challenges in integrating care underline the need for research on the mental models that characterize the behaviors of actors within health systems; the proposed framework offers a starting point for applying a cognitive perspective to health systems integration.

  19. Closed-Head TBI Model of Multiple Morbidity.

    Science.gov (United States)

    Thompson, Floyd J; Hou, Jiamei; Bose, Prodip K

    2016-01-01

    brain (Morales et al., Neuroscience 136:971-989, 2005; Foda and Marmarou, J Neurosurg 80:301-313, 1994; Kallakuri et al., Exp Brain Res 148:419-424, 2003). Accordingly, use of this preclinical model offers an opportunity for (a) gaining a greater understanding of the relationships of TBI induced diffuse axonal injuries and associated long term disabilities, and (b) to provide a platform for quantitative assessment of treatment interactions upon the trajectories of TBI-induced disabilities. Using the impact acceleration closed head TBI model to induce mild/moderate injuries in the rat, we have observed and quantitated multiple morbidities commonly observed following TBI in humans (Bose et al., J Neurotrauma 30:1177-1191, 2013). This chapter describes methods and protocols used for TBI-induced multiple morbidity involving cognitive dysfunction, balance instability, spasticity and gait, and anxiety-like disorder.

  20. State estimation of stochastic non-linear hybrid dynamic system using an interacting multiple model algorithm.

    Science.gov (United States)

    Elenchezhiyan, M; Prakash, J

    2015-09-01

    In this work, state estimation schemes for non-linear hybrid dynamic systems subjected to stochastic state disturbances and random errors in measurements using interacting multiple-model (IMM) algorithms are formulated. In order to compute both discrete modes and continuous state estimates of a hybrid dynamic system either an IMM extended Kalman filter (IMM-EKF) or an IMM based derivative-free Kalman filters is proposed in this study. The efficacy of the proposed IMM based state estimation schemes is demonstrated by conducting Monte-Carlo simulation studies on the two-tank hybrid system and switched non-isothermal continuous stirred tank reactor system. Extensive simulation studies reveal that the proposed IMM based state estimation schemes are able to generate fairly accurate continuous state estimates and discrete modes. In the presence and absence of sensor bias, the simulation studies reveal that the proposed IMM unscented Kalman filter (IMM-UKF) based simultaneous state and parameter estimation scheme outperforms multiple-model UKF (MM-UKF) based simultaneous state and parameter estimation scheme.

  1. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

    DEFF Research Database (Denmark)

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H

    2016-01-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

  2. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

    DEFF Research Database (Denmark)

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H;

    2016-01-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies and fo...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

  3. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    Science.gov (United States)

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  4. Multilocus sequence typing of genital Chlamydia trachomatis in Norway reveals multiple new sequence types and a large genetic diversity.

    Directory of Open Access Journals (Sweden)

    Kirsten Gravningen

    Full Text Available BACKGROUND: The Chlamydia trachomatis incidence rate in Finnmark, the most northern and sparsely populated county in Norway, has been twice the national average. This population based cross-sectional study among Finnmark high school students had the following aims: i to examine distribution of multilocus sequence types (STs of C. trachomatis in a previously unmapped area, ii to compare chlamydia genetic diversity in Finnmark with that of two urban regions, and iii to compare discriminatory capacity of multilocus sequence typing (MLST with conventional ompA sequencing in a large number of chlamydia specimens. METHODOLOGY: ompA sequencing and a high-resolution MLST system based on PCR amplification and DNA sequencing of five highly variable genetic regions were used. Eighty chlamydia specimens from adolescents aged 15-20 years in Finnmark were collected in five high schools (n = 60 and from routine clinical samples in the laboratory (n = 20. These were compared to routine clinical samples from adolescents in Tromsø (n = 80 and Trondheim (n = 88, capitals of North and Central Norway, respectively. PRINCIPAL FINDINGS: ompA sequencing detected 11 genotypes in 248 specimens from all three areas. MLST displayed 50 STs providing a five-fold higher resolution. Two-thirds of all STs were novel. The common ompA E/Bour genotype comprised 46% and resolved into 24 different STs. MLST identified the Swedish new variant of C. trachomatis not discriminated by ompA sequencing. Simpson's discriminatory index (D was 0.93 for MLST, while a corrected D(c was 0.97. There were no statistically significant differences in ST genetic diversity between geographic areas. Finnmark had an atypical genovar distribution with G being predominant. This was mainly due to expansion of specific STs of which the novel ST161 was unique for Finnmark. CONCLUSIONS/SIGNIFICANCE: MLST revealed multiple new STs and a larger genetic diversity in comparison to ompA sequencing

  5. Nonlinear Modeling and Identification of an Aluminum Honeycomb Panel with Multiple Bolts

    Directory of Open Access Journals (Sweden)

    Yongpeng Chu

    2016-01-01

    Full Text Available This paper focuses on the nonlinear dynamics modeling and parameter identification of an Aluminum Honeycomb Panel (AHP with multiple bolted joints. Finite element method using eight-node solid elements is exploited to model the panel and the bolted connection interface as a homogeneous, isotropic plate and as a thin layer of nonlinear elastic-plastic material, respectively. The material properties of a thin layer are defined by a bilinear elastic plastic model, which can describe the energy dissipation and softening phenomena in the bolted joints under nonlinear states. Experimental tests at low and high excitation levels are performed to reveal the dynamic characteristics of the bolted structure. In particular, the linear material parameters of the panel are identified via experimental tests at low excitation levels, whereas the nonlinear material parameters of the thin layer are updated by using the genetic algorithm to minimize the residual error between the measured and the simulation data at a high excitation level. It is demonstrated by comparing the frequency responses of the updated FEM and the experimental system that the thin layer of bilinear elastic-plastic material is very effective for modeling the nonlinear joint interface of the assembled structure with multiple bolts.

  6. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    Energy Technology Data Exchange (ETDEWEB)

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  7. Multiple cooling episodes in the Central Tarim (Northwest China) revealed by apatite fission track analysis and vitrinite reflectance data

    Science.gov (United States)

    Chang, Jian; Qiu, Nansheng; Song, Xinying; Li, Huili

    2016-06-01

    Apatite fission track and vitrinite reflectance are integrated for the first time to study the cooling history in the Central Tarim, northwest China. The paleo-temperature profiles from vitrinite reflectance data of the Z1 and Z11 wells showed a linear relationship with depth, suggesting an approximately 24.8 °C/km paleo-geothermal gradient and 2700-3900 m of erosion during the Early Mesozoic. The measured apatite fission track ages from well Z2 in the Central Tarim range from 39 to 159 Ma and effectively record the Meso-Cenozoic cooling events that occurred in Central Tarim. Moreover, two cooling events at 190-140 Ma in the Early Jurassic-Early Cretaceous and 80-45 Ma in the Late Cretaceous-Paleocene revealed by measured AFT data and thermal modeling results are related to the collisions of the Qiangtang-Lhasa terranes and the Greater India Plate with the southern margin of the Eurasian Plate, respectively. This study provides new insights into the tectonic evolution of the Tarim Basin (and more broadly Central Asia) and for hydrocarbon generation and exploration in the Central Tarim.

  8. Bayesian inference based modelling for gene transcriptional dynamics by integrating multiple source of knowledge

    Directory of Open Access Journals (Sweden)

    Wang Shu-Qiang

    2012-07-01

    Full Text Available Abstract Background A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. Numerous methods have been developed for reconstructing gene regulatory networks from expression data. However, most of them are based on coarse grained qualitative models, and cannot provide a quantitative view of regulatory systems. Results A binding affinity based regulatory model is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity and the activity level of transcription factor (TF are incorporated into a general learning model. The sequence features of the promoter and the possible occupancy of nucleosomes are exploited to estimate the binding probability of regulators. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. Conclusions We testify the proposed approach on two real-world microarray datasets. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than previous models can do.

  9. Multiple Time Courses of Vestibular Set-Point Adaptation Revealed by Sustained Magnetic Field Stimulation of the Labyrinth.

    Science.gov (United States)

    Jareonsettasin, Prem; Otero-Millan, Jorge; Ward, Bryan K; Roberts, Dale C; Schubert, Michael C; Zee, David S

    2016-05-23

    A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little is known about another essential form of learning, "set-point" adaptation. Set-point adaptation balances tonic activity so that reciprocally acting, agonist and antagonist muscles have a stable platform from which to launch accurate movements. Here, we use the vestibulo-ocular reflex-a simple behavior that stabilizes the position of the eye while the head is moving-to investigate how tonic activity is adapted toward a new set point to prevent eye drift when the head is still [3, 4]. Set-point adaptation was elicited with magneto-hydrodynamic vestibular stimulation (MVS) by placing normal humans in a 7T MRI for 90 min. MVS is ideal for prolonged labyrinthine activation because it mimics constant head acceleration and induces a sustained nystagmus similar to natural vestibular lesions [5, 6]. The MVS-induced nystagmus diminished slowly but incompletely over multiple timescales. We propose a new adaptation hypothesis, using a cascade of imperfect mathematical integrators, that reproduces the response to MVS (and more natural chair rotations), including the gradual decrease in nystagmus as the set point changes over progressively longer time courses. MVS set-point adaptation is a biological model with applications to basic neurophysiological research into all types of movements [7], functional brain imaging [8], and treatment of vestibular and higher-level attentional disorders by introducing new biases to counteract pathological ones [9].

  10. Verification of road databases using multiple road models

    Science.gov (United States)

    Ziems, Marcel; Rottensteiner, Franz; Heipke, Christian

    2017-08-01

    In this paper a new approach for automatic road database verification based on remote sensing images is presented. In contrast to existing methods, the applicability of the new approach is not restricted to specific road types, context areas or geographic regions. This is achieved by combining several state-of-the-art road detection and road verification approaches that work well under different circumstances. Each one serves as an independent module representing a unique road model and a specific processing strategy. All modules provide independent solutions for the verification problem of each road object stored in the database in form of two probability distributions, the first one for the state of a database object (correct or incorrect), and a second one for the state of the underlying road model (applicable or not applicable). In accordance with the Dempster-Shafer Theory, both distributions are mapped to a new state space comprising the classes correct, incorrect and unknown. Statistical reasoning is applied to obtain the optimal state of a road object. A comparison with state-of-the-art road detection approaches using benchmark datasets shows that in general the proposed approach provides results with larger completeness. Additional experiments reveal that based on the proposed method a highly reliable semi-automatic approach for road data base verification can be designed.

  11. The Answering Process for Multiple-Choice Questions in Collaborative Learning: A Mathematical Learning Model Analysis

    Science.gov (United States)

    Nakamura, Yasuyuki; Nishi, Shinnosuke; Muramatsu, Yuta; Yasutake, Koichi; Yamakawa, Osamu; Tagawa, Takahiro

    2014-01-01

    In this paper, we introduce a mathematical model for collaborative learning and the answering process for multiple-choice questions. The collaborative learning model is inspired by the Ising spin model and the model for answering multiple-choice questions is based on their difficulty level. An intensive simulation study predicts the possibility of…

  12. A Fuzzy Logic Framework for Integrating Multiple Learned Models

    Energy Technology Data Exchange (ETDEWEB)

    Hartog, Bobi Kai Den [Univ. of Nebraska, Lincoln, NE (United States)

    1999-03-01

    The Artificial Intelligence field of Integrating Multiple Learned Models (IMLM) explores ways to combine results from sets of trained programs. Aroclor Interpretation is an ill-conditioned problem in which trained programs must operate in scenarios outside their training ranges because it is intractable to train them completely. Consequently, they fail in ways related to the scenarios. We developed a general-purpose IMLM solution, the Combiner, and applied it to Aroclor Interpretation. The Combiner's first step, Scenario Identification (M), learns rules from very sparse, synthetic training data consisting of results from a suite of trained programs called Methods. S1 produces fuzzy belief weights for each scenario by approximately matching the rules. The Combiner's second step, Aroclor Presence Detection (AP), classifies each of three Aroclors as present or absent in a sample. The third step, Aroclor Quantification (AQ), produces quantitative values for the concentration of each Aroclor in a sample. AP and AQ use automatically learned empirical biases for each of the Methods in each scenario. Through fuzzy logic, AP and AQ combine scenario weights, automatically learned biases for each of the Methods in each scenario, and Methods' results to determine results for a sample.

  13. Robust hierarchical state-space models reveal diel variation in travel rates of migrating leatherback turtles.

    Science.gov (United States)

    Jonsen, Ian D; Myers, Ransom A; James, Michael C

    2006-09-01

    1. Biological and statistical complexity are features common to most ecological data that hinder our ability to extract meaningful patterns using conventional tools. Recent work on implementing modern statistical methods for analysis of such ecological data has focused primarily on population dynamics but other types of data, such as animal movement pathways obtained from satellite telemetry, can also benefit from the application of modern statistical tools. 2. We develop a robust hierarchical state-space approach for analysis of multiple satellite telemetry pathways obtained via the Argos system. State-space models are time-series methods that allow unobserved states and biological parameters to be estimated from data observed with error. We show that the approach can reveal important patterns in complex, noisy data where conventional methods cannot. 3. Using the largest Atlantic satellite telemetry data set for critically endangered leatherback turtles, we show that the diel pattern in travel rates of these turtles changes over different phases of their migratory cycle. While foraging in northern waters the turtles show similar travel rates during day and night, but on their southward migration to tropical waters travel rates are markedly faster during the day. These patterns are generally consistent with diving data, and may be related to changes in foraging behaviour. Interestingly, individuals that migrate southward to breed generally show higher daytime travel rates than individuals that migrate southward in a non-breeding year. 4. Our approach is extremely flexible and can be applied to many ecological analyses that use complex, sequential data.

  14. On testing an unspecified function through a linear mixed effects model with multiple variance components.

    Science.gov (United States)

    Wang, Yuanjia; Chen, Huaihou

    2012-12-01

    We examine a generalized F-test of a nonparametric function through penalized splines and a linear mixed effects model representation. With a mixed effects model representation of penalized splines, we imbed the test of an unspecified function into a test of some fixed effects and a variance component in a linear mixed effects model with nuisance variance components under the null. The procedure can be used to test a nonparametric function or varying-coefficient with clustered data, compare two spline functions, test the significance of an unspecified function in an additive model with multiple components, and test a row or a column effect in a two-way analysis of variance model. Through a spectral decomposition of the residual sum of squares, we provide a fast algorithm for computing the null distribution of the test, which significantly improves the computational efficiency over bootstrap. The spectral representation reveals a connection between the likelihood ratio test (LRT) in a multiple variance components model and a single component model. We examine our methods through simulations, where we show that the power of the generalized F-test may be higher than the LRT, depending on the hypothesis of interest and the true model under the alternative. We apply these methods to compute the genome-wide critical value and p-value of a genetic association test in a genome-wide association study (GWAS), where the usual bootstrap is computationally intensive (up to 10(8) simulations) and asymptotic approximation may be unreliable and conservative. © 2012, The International Biometric Society.

  15. Inflammation modulates anxiety in an animal model of multiple sclerosis.

    Science.gov (United States)

    Peruga, Isabella; Hartwig, Silvia; Thöne, Jan; Hovemann, Bernhard; Gold, Ralf; Juckel, Georg; Linker, Ralf A

    2011-06-20

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by inflammation, but also degenerative changes. Besides neurological deficits, the rate of affective disorders such as depression and anxiety is at least six fold increased. Many aspects of MS can be mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (MOG-EAE). Here we investigate behavioral changes in C57BL/6 mice suffering from mild MOG-EAE. In the later phase of the disease, mice were subjected to behavioral tests including the light-dark-box (LD Box), the acoustic startle response (SR) with a pre-pulse inhibition protocol as well as the learned helplessness (LH) paradigm. Behavioral data were correlated with the motor performance in an open field and rotarod test (RR). In the RR and open field, there was no significant difference in the motor performance between controls and mice suffering from mild MOG-EAE. Yet EAE mice displayed an increased anxiety-like behavior with a 23% reduction of the time spent in the bright compartment of the LD Box as well as an increased SR. In the LH paradigm, mice suffering from MOG-EAE were twice as much prone to depressive-like behavior. These changes correlate with an increase of hippocampal tissue tumor necrosis factor alpha levels and neuronal loss in the hippocampus. Modulation of monoaminergic transmission by chronic application of the antidepressant amitriptyline resulted in a decreased startle reaction and increased hippocampal norepinephrine levels. These data imply that chronic inflammation in the CNS may impact on emotional responses in rodent models of anxiety. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Calcium Intervention Ameliorates Experimental Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dariush Haghmorad

    2014-05-01

    Full Text Available Objective: Multiple sclerosis (MS is the most common inflammatory disease of the CNS. Experimental autoimmune encephalomyelitis (EAE is a widely used model for MS. In the present research, our aim was to test the therapeutic efficacy of Calcium (Ca in an experimental model of MS. Methods: In this study the experiment was done on C57BL/6 mice. EAE was induced using 200 μg of the MOG35-55 peptide emulsified in CFA and injected subcutaneously on day 0 over two flank areas. In addition, 250 ng of pertussis toxin was injected on days 0 and 2. In the treatment group, 30 mg/kg Ca was administered intraperitoneally four times at regular 48 hour intervals. The mice were sacrificed 21 days after EAE induction and blood samples were taken from their hearts. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. Results: Our results showed that treatment with Ca caused a significant reduction in the severity of the EAE. Histological analysis indicated that there was no plaque in brain sections of Ca treated group of mice whereas 4 ± 1 plaques were detected in brain sections of controls. The density of mononuclear infiltration in the CNS of Ca treated mice was lower than in controls. The serum level of Nitric Oxide in the treatment group was lower than in the control group but was not significant. Moreover, the levels of IFN-γ in cell culture supernatant of splenocytes in treated mice were significantly lower than in the control group. Conclusion: The data indicates that Ca intervention can effectively attenuate EAE progression.

  17. A general additive-multiplicative rates model for recurrent event data

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this article, we propose a general additive-multiplicative rates model for recurrent event data. The proposed model includes the additive rates and multiplicative rates models as special cases. For the inference on the model parameters, estimating equation approaches are developed, and asymptotic properties of the proposed estimators are established through modern empirical process theory. In addition, an illustration with multiple-infection data from a clinic study on chronic granulomatous disease is provided.

  18. Multiple linear regression models of urban runoff pollutant load and event mean concentration considering rainfall variables.

    Science.gov (United States)

    Maniquiz, Marla C; Lee, Soyoung; Kim, Lee-Hyung

    2010-01-01

    Rainfall is an important factor in estimating the event mean concentration (EMC) which is used to quantify the washed-off pollutant concentrations from non-point sources (NPSs). Pollutant loads could also be calculated using rainfall, catchment area and runoff coefficient. In this study, runoff quantity and quality data gathered from a 28-month monitoring conducted on the road and parking lot sites in Korea were evaluated using multiple linear regression (MLR) to develop equations for estimating pollutant loads and EMCs as a function of rainfall variables. The results revealed that total event rainfall and average rainfall intensity are possible predictors of pollutant loads. Overall, the models are indicators of the high uncertainties of NPSs; perhaps estimation of EMCs and loads could be accurately obtained by means of water quality sampling or a long-term monitoring is needed to gather more data that can be used for the development of estimation models.

  19. Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium

    Directory of Open Access Journals (Sweden)

    Bhattacharyya-Pakrasi Maitrayee

    2010-08-01

    Full Text Available Abstract Background Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. Synechocystis sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in Synechocystis have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes. Results We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in Synechocystis. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR, are commonly regulated under most perturbations. The CTR contains nearly 12% of Synechocystis genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in Synechocystis under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes. Conclusion We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This

  20. Optimization of end-members used in multiple linear regression geochemical mixing models

    Science.gov (United States)

    Dunlea, Ann G.; Murray, Richard W.

    2015-11-01

    Tracking marine sediment provenance (e.g., of dust, ash, hydrothermal material, etc.) provides insight into contemporary ocean processes and helps construct paleoceanographic records. In a simple system with only a few end-members that can be easily quantified by a unique chemical or isotopic signal, chemical ratios and normative calculations can help quantify the flux of sediment from the few sources. In a more complex system (e.g., each element comes from multiple sources), more sophisticated mixing models are required. MATLAB codes published in Pisias et al. solidified the foundation for application of a Constrained Least Squares (CLS) multiple linear regression technique that can use many elements and several end-members in a mixing model. However, rigorous sensitivity testing to check the robustness of the CLS model is time and labor intensive. MATLAB codes provided in this paper reduce the time and labor involved and facilitate finding a robust and stable CLS model. By quickly comparing the goodness of fit between thousands of different end-member combinations, users are able to identify trends in the results that reveal the CLS solution uniqueness and the end-member composition precision required for a good fit. Users can also rapidly check that they have the appropriate number and type of end-members in their model. In the end, these codes improve the user's confidence that the final CLS model(s) they select are the most reliable solutions. These advantages are demonstrated by application of the codes in two case studies of well-studied datasets (Nazca Plate and South Pacific Gyre).

  1. Evolutionary history of the fish genus Astyanax Baird & Girard (1854 (Actinopterygii, Characidae in Mesoamerica reveals multiple morphological homoplasies

    Directory of Open Access Journals (Sweden)

    Doadrio Ignacio

    2008-12-01

    Full Text Available Abstract Background Mesoamerica is one of the world's most complex biogeographical regions, mostly due to its complex geological history. This complexity has led to interesting biogeographical processes that have resulted in the current diversity and distribution of fauna in the region. The fish genus Astyanax represents a useful model to assess biogeographical hypotheses due to it being one of the most diverse and widely distributed freshwater fish species in the New World. We used mitochondrial and nuclear DNA to evaluate phylogenetic relationships within the genus in Mesoamerica, and to develop historical biogeographical hypotheses to explain its current distribution. Results Analysis of the entire mitochondrial cytochrome b (Cytb gene in 208 individuals from 147 localities and of a subset of individuals for three mitochondrial genes (Cytb, 16 S, and COI and a single nuclear gene (RAG1 yielded similar topologies, recovering six major groups with significant phylogeographic structure. Populations from North America and Upper Central America formed a monophyletic group, while Middle Central America showed evidence of rapid radiation with incompletely resolved relationships. Lower Central America lineages showed a fragmented structure, with geographically restricted taxa showing high levels of molecular divergence. All Bramocharax samples grouped with their sympatric Astyanax lineages (in some cases even with allopatric Astyanax populations, with less than 1% divergence between them. These results suggest a homoplasic nature to the trophic specializations associated with Bramocharax ecomorphs, which seem to have arisen independently in different Astyanax lineages. We observed higher taxonomic diversity compared to previous phylogenetic studies of the Astyanax genus. Colonization of Mesoamerica by Astyanax before the final closure of the Isthmus of Panama (3.3 Mya explains the deep level of divergence detected in Lower Central America. The

  2. Evolutionary history of the fish genus Astyanax Baird & Girard (1854) (Actinopterygii, Characidae) in Mesoamerica reveals multiple morphological homoplasies

    Science.gov (United States)

    2008-01-01

    Background Mesoamerica is one of the world's most complex biogeographical regions, mostly due to its complex geological history. This complexity has led to interesting biogeographical processes that have resulted in the current diversity and distribution of fauna in the region. The fish genus Astyanax represents a useful model to assess biogeographical hypotheses due to it being one of the most diverse and widely distributed freshwater fish species in the New World. We used mitochondrial and nuclear DNA to evaluate phylogenetic relationships within the genus in Mesoamerica, and to develop historical biogeographical hypotheses to explain its current distribution. Results Analysis of the entire mitochondrial cytochrome b (Cytb) gene in 208 individuals from 147 localities and of a subset of individuals for three mitochondrial genes (Cytb, 16 S, and COI) and a single nuclear gene (RAG1) yielded similar topologies, recovering six major groups with significant phylogeographic structure. Populations from North America and Upper Central America formed a monophyletic group, while Middle Central America showed evidence of rapid radiation with incompletely resolved relationships. Lower Central America lineages showed a fragmented structure, with geographically restricted taxa showing high levels of molecular divergence. All Bramocharax samples grouped with their sympatric Astyanax lineages (in some cases even with allopatric Astyanax populations), with less than 1% divergence between them. These results suggest a homoplasic nature to the trophic specializations associated with Bramocharax ecomorphs, which seem to have arisen independently in different Astyanax lineages. We observed higher taxonomic diversity compared to previous phylogenetic studies of the Astyanax genus. Colonization of Mesoamerica by Astyanax before the final closure of the Isthmus of Panama (3.3 Mya) explains the deep level of divergence detected in Lower Central America. The colonization of Upper

  3. Evolutionary history of the fish genus Astyanax Baird & Girard (1854) (Actinopterygii, Characidae) in Mesoamerica reveals multiple morphological homoplasies.

    Science.gov (United States)

    Ornelas-García, Claudia Patricia; Domínguez-Domínguez, Omar; Doadrio, Ignacio

    2008-12-22

    Mesoamerica is one of the world's most complex biogeographical regions, mostly due to its complex geological history. This complexity has led to interesting biogeographical processes that have resulted in the current diversity and distribution of fauna in the region. The fish genus Astyanax represents a useful model to assess biogeographical hypotheses due to it being one of the most diverse and widely distributed freshwater fish species in the New World. We used mitochondrial and nuclear DNA to evaluate phylogenetic relationships within the genus in Mesoamerica, and to develop historical biogeographical hypotheses to explain its current distribution. Analysis of the entire mitochondrial cytochrome b (Cytb) gene in 208 individuals from 147 localities and of a subset of individuals for three mitochondrial genes (Cytb, 16 S, and COI) and a single nuclear gene (RAG1) yielded similar topologies, recovering six major groups with significant phylogeographic structure. Populations from North America and Upper Central America formed a monophyletic group, while Middle Central America showed evidence of rapid radiation with incompletely resolved relationships. Lower Central America lineages showed a fragmented structure, with geographically restricted taxa showing high levels of molecular divergence. All Bramocharax samples grouped with their sympatric Astyanax lineages (in some cases even with allopatric Astyanax populations), with less than 1% divergence between them. These results suggest a homoplasic nature to the trophic specializations associated with Bramocharax ecomorphs, which seem to have arisen independently in different Astyanax lineages. We observed higher taxonomic diversity compared to previous phylogenetic studies of the Astyanax genus. Colonization of Mesoamerica by Astyanax before the final closure of the Isthmus of Panama (3.3 Mya) explains the deep level of divergence detected in Lower Central America. The colonization of Upper Mesoamerica apparently

  4. Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction

    Directory of Open Access Journals (Sweden)

    Dai Hongying

    2013-01-01

    Full Text Available Abstract Background Multifactor Dimensionality Reduction (MDR has been widely applied to detect gene-gene (GxG interactions associated with complex diseases. Existing MDR methods summarize disease risk by a dichotomous predisposing model (high-risk/low-risk from one optimal GxG interaction, which does not take the accumulated effects from multiple GxG interactions into account. Results We propose an Aggregated-Multifactor Dimensionality Reduction (A-MDR method that exhaustively searches for and detects significant GxG interactions to generate an epistasis enriched gene network. An aggregated epistasis enriched risk score, which takes into account multiple GxG interactions simultaneously, replaces the dichotomous predisposing risk variable and provides higher resolution in the quantification of disease susceptibility. We evaluate this new A-MDR approach in a broad range of simulations. Also, we present the results of an application of the A-MDR method to a data set derived from Juvenile Idiopathic Arthritis patients treated with methotrexate (MTX that revealed several GxG interactions in the folate pathway that were associated with treatment response. The epistasis enriched risk score that pooled information from 82 significant GxG interactions distinguished MTX responders from non-responders with 82% accuracy. Conclusions The proposed A-MDR is innovative in the MDR framework to investigate aggregated effects among GxG interactions. New measures (pOR, pRR and pChi are proposed to detect multiple GxG interactions.

  5. Model Vehicle Routing Problem dengan Karakteristik Rute Majemuk, Multiple Time Windows, Multiple Products dan Heterogeneous Fleet untuk Depot Tunggal

    Directory of Open Access Journals (Sweden)

    Ary Arvianto

    2014-01-01

    Full Text Available In this paper we developed a VRP model for multiple routes, multiple time windows for multiple products and heterogeneous vehicles. The solution were constructed using a heuristic approach, i.e, a sequential insertion algorithm. Additionally, this model is applied to solve fuel distributions for eight customers in East Nusa Tenggara. It needs two tankers with capacity of 4700 kilo liters, so that those distributions can be accomplished with a minimum number of vehicles, total completion time, and range of completion time. The result of this study shows that for a heterogeneous vehicles problem, a vehicle with the largest capacity may not necessarily be the vehicle that provides an optimal solution. Moreover, advance trials should be conducted by providing a limited number of tankers for each tanker capacity, so the description of heterogeneous vehicles becomes more visible. In the future research, the solution will be improved by utilizing relocation techniques.

  6. Hydrostratigraphic modelling using multiple-point statistics and airborne transient electromagnetic methods

    DEFF Research Database (Denmark)

    Barfod, Adrian; Straubhaar, Julien; Høyer, Anne-Sophie

    2017-01-01

    Creating increasingly realistic hydrological models involves the inclusion of additional geological and geophysical data in the hydrostratigraphic modelling procedure. Using Multiple Point Statistics (MPS) for stochastic hydrostratigraphic modelling provides a degree of flexibility that allows th...

  7. Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

    Directory of Open Access Journals (Sweden)

    Masanao Sato

    Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

  8. Phylogeny and evolutionary histories of Pyrus L. revealed by phylogenetic trees and networks based on data from multiple DNA sequences

    Science.gov (United States)

    Reconstructing the phylogeny of Pyrus has been difficult due to the wide distribution of the genus and lack of informative data. In this study, we collected 110 accessions representing 25 Pyrus species and constructed both phylogenetic trees and phylogenetic networks based on multiple DNA sequence d...

  9. Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

    NARCIS (Netherlands)

    Sathitruangsak, C.; Righolt, C.H.; Klewes, L.; Tammur, P.; Ilus, T.; Tamm, A.; Punab, M.; Olujohungbe, A.; Mai, S.

    2015-01-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control

  10. Semantics of Temporal Models with Multiple Temporal Dimensions

    DEFF Research Database (Denmark)

    Kraft, Peter; Sørensen, Jens Otto

    Semantics of temporal models with multi temporal dimensions are examined progressing from non-temporal models unto uni-temporal, and further unto bi- and tri-temporal models. An example of a uni-temporal model is the valid time model, an example of a bi-temporal model is the valid time/transactio......Semantics of temporal models with multi temporal dimensions are examined progressing from non-temporal models unto uni-temporal, and further unto bi- and tri-temporal models. An example of a uni-temporal model is the valid time model, an example of a bi-temporal model is the valid time....../transaction time model, and finally an example of a tri-temporal model is a model with valid time, decision time and transaction time dimensions. The semantics are at first specified at the highest conceptual level possible by a graphical notation. Next, the conceptual models are translated into lower level models...

  11. THE ROLE OF PARASYMPATHETIC AUTONOMIC REGULATION IN ENSURING OF RATS’ RESISTANCE IN THE MODEL OF MULTIPLE ORGAN DYSFUNCTION SYNDROM

    Directory of Open Access Journals (Sweden)

    I. A. Khrypachenko

    2015-06-01

    Full Text Available To assess contribution of autonomic regulation in multiple organ dysfunction syndrome (MODS survival ensuring and to test hypothesis about possible correction of clinical course by modulating the activity of parasympathetic influences we performed experiments on rats’ model of the MODS. It was determined that nonresistant animals differentiated by less intensity of parasympathetic regulation response. It was revealed that stimulation of cholinergic system decrease lethality in rats, and inhibits the power of high frequency regulatory effects on the heart rate.

  12. Description of light charged particle multiplicities in the framework of dinuclear system model

    Directory of Open Access Journals (Sweden)

    Antonenko N.V.

    2012-12-01

    Full Text Available In the framework of dinuclear system (DNS model we calculate the light charged particle (LCP multiplicities produced in fusion and quasifission reactions and their kinetic energy spectra. Calculations indicate that with increasing bombarding energy the ratio of LCP multiplicity from fragments MFF to corresponding LCP multiplicity from compound nucleus (CN MCN strongly increases.

  13. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

    Directory of Open Access Journals (Sweden)

    Rakhshan Ihsan

    Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

  14. On the multiplicity distribution in statistical model: (I) negative binomial distribution

    CERN Document Server

    Xu, Hao-jie

    2016-01-01

    With the distribution of principal thermodynamic variables (e.g.,volume) and the probability condition from reference multiplicity, we develop an improved baseline measure for multiplicity distribution in statistical model to replace the traditional Poisson expectations. We demonstrate the mismatches between experimental measurements and previous theoretical calculations on multiplicity distributions. We derive a general expression for multiplicity distribution, i.e. a conditional probability distribution, in statistical model and calculate its cumulants under Poisson approximation in connection with recent data for multiplicity fluctuations. We find that probability condition from reference multiplicity are crucial to explain the centrality resolution effect in experiment. With the improved baseline measure for multiplicity distribution, we can quantitatively reproduce the cumulants (cumulant products) for multiplicity distribution of total (net) charges measured in experiments.

  15. Remyelination induced by a DNA aptamer in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Branislav Nastasijevic

    Full Text Available Multiple sclerosis (MS is a debilitating inflammatory disease of the central nervous system (CNS characterized by local destruction of the insulating myelin surrounding neuronal axons. With more than 200 million MS patients worldwide, the absence of treatments that prevent progression or induce repair poses a major challenge. Anti-inflammatory therapies have met with limited success only in preventing relapses. Previous screening of human serum samples revealed natural IgM antibodies that bind oligodendrocytes and promote both cell signaling and remyelination of CNS lesions in an MS model involving chronic infection of susceptible mice by Theiler's encephalomyelitis virus and in the lysolecithin model of focal demyelination. This intriguing result raises the possibility that molecules with binding specificity for oligodendrocytes or myelin components may promote therapeutic remyelination in MS. Because of the size and complexity of IgM antibodies, it is of interest to identify smaller myelin-specific molecules with the ability to promote remyelination in vivo. Here we show that a 40-nucleotide single-stranded DNA aptamer selected for affinity to murine myelin shows this property. This aptamer binds multiple myelin components in vitro. Peritoneal injection of this aptamer results in distribution to CNS tissues and promotes remyelination of CNS lesions in mice infected by Theiler's virus. Interestingly, the selected DNA aptamer contains guanosine-rich sequences predicted to induce folding involving guanosine quartet structures. Relative to monoclonal antibodies, DNA aptamers are small, stable, and non-immunogenic, suggesting new possibilities for MS treatment.

  16. Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

    DEFF Research Database (Denmark)

    Vishnubalaji, R; Hamam, R; Abdulla, M-H;

    2015-01-01

    upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF......-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by micro...... in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks...

  17. Tools and Models for Integrating Multiple Cellular Networks

    Energy Technology Data Exchange (ETDEWEB)

    Gerstein, Mark [Yale Univ., New Haven, CT (United States). Gerstein Lab.

    2015-11-06

    In this grant, we have systematically investigated the integrated networks, which are responsible for the coordination of activity between metabolic pathways in prokaryotes. We have developed several computational tools to analyze the topology of the integrated networks consisting of metabolic, regulatory, and physical interaction networks. The tools are all open-source, and they are available to download from Github, and can be incorporated in the Knowledgebase. Here, we summarize our work as follow. Understanding the topology of the integrated networks is the first step toward understanding its dynamics and evolution. For Aim 1 of this grant, we have developed a novel algorithm to determine and measure the hierarchical structure of transcriptional regulatory networks [1]. The hierarchy captures the direction of information flow in the network. The algorithm is generally applicable to regulatory networks in prokaryotes, yeast and higher organisms. Integrated datasets are extremely beneficial in understanding the biology of a system in a compact manner due to the conflation of multiple layers of information. Therefore for Aim 2 of this grant, we have developed several tools and carried out analysis for integrating system-wide genomic information. To make use of the structural data, we have developed DynaSIN for protein-protein interactions networks with various dynamical interfaces [2]. We then examined the association between network topology with phenotypic effects such as gene essentiality. In particular, we have organized E. coli and S. cerevisiae transcriptional regulatory networks into hierarchies. We then correlated gene phenotypic effects by tinkering with different layers to elucidate which layers were more tolerant to perturbations [3]. In the context of evolution, we also developed a workflow to guide the comparison between different types of biological networks across various species using the concept of rewiring [4], and Furthermore, we have developed

  18. Multiple giant coronary aneurysms arising from coronary istula to the pulmonary artery revealed in aorta CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam [Dept. of Radiology, Dong A University Hospital, Dong-A University College of Medicine, Busan (Korea, Republic of); Lee, Jong Min [Dept. of Radiology, Kyungpook National University Hospital, Kyungpook National University College of Medicine, Daegu (Korea, Republic of)

    2015-12-15

    Coronary fistula is a rare coronary abnormality through which blood drains into the cardiac chamber, great vessel or other vessels. In addition, giant aneurysm arising from coronary fistula is rare pathologic manifestation. Herein, we presented a rare case of multiple giant coronary artery aneurysms arising from coronary to pulmonary artery fistula in a 79-year-old woman presenting with sudden loss of consciousness. The aneurysms were detected using thoracic computed tomography angiography and consequently confirmed by invasive coronary angiography.

  19. Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

    OpenAIRE

    Sathitruangsak, C.; Righolt, C.H.; Klewes, L.; Tammur, P.; Ilus, T.; Tamm, A; Punab, M.; Olujohungbe, A; Mai, S.

    2015-01-01

    ABSTRACT The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three‐dimensional structured illumination microscopy (3D‐SIM) increases the spatial r...

  20. A kinetic model for the internal motions of proteins: diffusion between multiple harmonic wells.

    Science.gov (United States)

    Amadei, A; de Groot, B L; Ceruso, M A; Paci, M; Di Nola, A; Berendsen, H J

    1999-05-15

    The dynamics of collective protein motions derived from Molecular Dynamics simulations have been studied for two small model proteins: initiation factor I and the B1 domain of Protein G. First, we compared the structural fluctuations, obtained by local harmonic approximations in different energy minima, with the ones revealed by large scale molecular dynamics (MD) simulations. It was found that a limited set of harmonic wells can be used to approximate the configurational fluctuations of these proteins, although any single harmonic approximation cannot properly describe their dynamics. Subsequently, the kinetics of the main (essential) collective protein motions were characterized. A dual-diffusion behavior was observed in which a fast type of diffusion switches to a much slower type in a typical time of about 1-3 ps. From these results, the large backbone conformational fluctuations of a protein may be considered as "hopping" between multiple harmonic wells on a basically flat free energy surface.

  1. Localization of a small change in a multiple scattering environment without modeling of the actual medium.

    Science.gov (United States)

    Rakotonarivo, S T; Walker, S C; Kuperman, W A; Roux, P

    2011-12-01

    A method to actively localize a small perturbation in a multiple scattering medium using a collection of remote acoustic sensors is presented. The approach requires only minimal modeling and no knowledge of the scatterer distribution and properties of the scattering medium and the perturbation. The medium is ensonified before and after a perturbation is introduced. The coherent difference between the measured signals then reveals all field components that have interacted with the perturbation. A simple single scatter filter (that ignores the presence of the medium scatterers) is matched to the earliest change of the coherent difference to localize the perturbation. Using a multi-source/receiver laboratory setup in air, the technique has been successfully tested with experimental data at frequencies varying from 30 to 60 kHz (wavelength ranging from 0.5 to 1 cm) for cm-scale scatterers in a scattering medium with a size two to five times bigger than its transport mean free path.

  2. Magnetic field modelling of machine and multiple machine systems using dynamic reluctance mesh modelling

    OpenAIRE

    Yao, Li

    2006-01-01

    This thesis concerns the modified and improved, time-stepping, dynamic reluctance mesh (DRM) modelling technique for machines and its application to multiple machine systems with their control algorithms. Improvements are suggested which enable the stable solution of the resulting complex non-linear equations. The concept of finite element (FE) derived, overlap-curves has been introduced to facilitate the evaluation of the air-gap reluctances linking the teeth on the rotor to those on the sta...

  3. Independent scattering model and velocity dispersion in trabecular bone: comparison with a multiple scattering model.

    Science.gov (United States)

    Haïat, G; Naili, S

    2011-02-01

    Speed of sound measurements are used clinically to assess bone strength. Trabecular bone is an attenuating composite material in which negative values of velocity dispersion have been measured; this behavior remaining poorly explained physically. The aim of this work is to describe the ultrasonic propagation in trabecular bone modeled by infinite cylinders immersed in a saturating matrix and to derive the physical determinants of velocity dispersion. An original homogenization model accounting for the coupling of independent scattering and absorption phenomena allows the computation of phase velocity and of dispersion while varying bone properties. The first step of the model consists in the computation of the attenuation coefficient at all frequencies. The second step of the model corresponds to the application of the general Kramers-Krönig relationship to derive the frequency dependence of phase velocity. The model predicts negative values of velocity dispersion in agreement with experimental results obtained in phantoms mimicking trabecular bone. In trabecular bone, only negative values of velocity dispersion are predicted by the model, which span within the range of values measured experimentally. However, the comparison of the present results with results obtained in Haiat et al. (J Acoust Soc Am 124:4047-4058, 2008) assuming multiple scattering indicates that accounting for multiple scattering phenomena leads to a better prediction of velocity dispersion in trabecular bone.

  4. The gene order on Human Chromosome 15 and Chicken Chromosome 10 reveal multiple inter- and intrachromosomal rearrangements

    NARCIS (Netherlands)

    Crooijmans, R.P.M.A.; Dijkhof, R.J.M.; Veenendaal, T.; Poel, van der J.J.; Groenen, M.A.M.

    2001-01-01

    Comparative mapping between the human and chicken genomes has revealed a striking conservation of synteny between the genomes of these two species, but the results have been based on low-resolution comparative maps. To address this conserved synteny in much more detail, a high-resolution human-chick

  5. Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2015-07-01

    Full Text Available The RNA polymerase II (Pol II is a eukaryotic enzyme that catalyzes the synthesis of the messenger RNA using a DNA template. Despite numerous biochemical and biophysical studies, it remains elusive whether the "secondary channel" is the only route for NTP to reach the active site of the enzyme or if the "main channel" could be an alternative. On this regard, crystallographic structures of Pol II have been extremely useful to understand the structural basis of transcription, however, the conformation of the unpaired non-template DNA part of the full transcription bubble (TB is still unknown. Since diffusion routes of the nucleoside triphosphate (NTP substrate through the main channel might overlap with the TB region, gaining structural information of the full TB is critical for a complete understanding of Pol II transcription process. In this study, we have built a structural model of Pol II with a complete transcription bubble based on multiple sources of existing structural data and used Molecular Dynamics (MD simulations together with structural analysis to shed light on NTP entry pathways. Interestingly, we found that although both channels have enough space to allow NTP loading, the percentage of MD conformations containing enough space for NTP loading through the secondary channel is twice higher than that of the main channel. Further energetic study based on MD simulations with NTP loaded in the channels has revealed that the diffusion of the NTP through the main channel is greatly disfavored by electrostatic repulsion between the NTP and the highly negatively charged backbones of nucleotides in the non-template DNA strand. Taken together, our results suggest that the secondary channel is the major route for NTP entry during Pol II transcription.

  6. Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes.

    Science.gov (United States)

    Zhang, Lu; Silva, Daniel-Adriano; Pardo-Avila, Fátima; Wang, Dong; Huang, Xuhui

    2015-07-01

    The RNA polymerase II (Pol II) is a eukaryotic enzyme that catalyzes the synthesis of the messenger RNA using a DNA template. Despite numerous biochemical and biophysical studies, it remains elusive whether the "secondary channel" is the only route for NTP to reach the active site of the enzyme or if the "main channel" could be an alternative. On this regard, crystallographic structures of Pol II have been extremely useful to understand the structural basis of transcription, however, the conformation of the unpaired non-template DNA part of the full transcription bubble (TB) is still unknown. Since diffusion routes of the nucleoside triphosphate (NTP) substrate through the main channel might overlap with the TB region, gaining structural information of the full TB is critical for a complete understanding of Pol II transcription process. In this study, we have built a structural model of Pol II with a complete transcription bubble based on multiple sources of existing structural data and used Molecular Dynamics (MD) simulations together with structural analysis to shed light on NTP entry pathways. Interestingly, we found that although both channels have enough space to allow NTP loading, the percentage of MD conformations containing enough space for NTP loading through the secondary channel is twice higher than that of the main channel. Further energetic study based on MD simulations with NTP loaded in the channels has revealed that the diffusion of the NTP through the main channel is greatly disfavored by electrostatic repulsion between the NTP and the highly negatively charged backbones of nucleotides in the non-template DNA strand. Taken together, our results suggest that the secondary channel is the major route for NTP entry during Pol II transcription.

  7. PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis : comparison of [C-11]MeDAS, [C-11]CIC and [C-11]PIB

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Copray, Sjef; Sijbesma, Jurgen W. A.; Willemsen, Antoon T. M.; Buchpiguel, Carlos A.; Dierckx, Rudi A. J. O.; de Vries, Erik F. J.

    2014-01-01

    PURPOSE: In this study, we compared the ability of [(11)C]CIC, [(11)C]MeDAS and [(11)C]PIB to reveal temporal changes in myelin content in focal lesions in the lysolecithin rat model of multiple sclerosis. Pharmacokinetic modelling was performed to determine the best method to quantify tracer uptake

  8. Modelling and Verification of Multiple UAV Mission Using SMV

    CERN Document Server

    Sirigineedi, Gopinadh; White, Brian A; Zbikowski, Rafal

    2010-01-01

    Model checking has been used to verify the correctness of digital circuits, security protocols, communication protocols, as they can be modelled by means of finite state transition model. However, modelling the behaviour of hybrid systems like UAVs in a Kripke model is challenging. This work is aimed at capturing the behaviour of an UAV performing cooperative search mission into a Kripke model, so as to verify it against the temporal properties expressed in Computation Tree Logic (CTL). SMV model checker is used for the purpose of model checking.

  9. Modelling and Verification of Multiple UAV Mission Using SMV

    Directory of Open Access Journals (Sweden)

    Gopinadh Sirigineedi

    2010-03-01

    Full Text Available Model checking has been used to verify the correctness of digital circuits, security protocols, communication protocols, as they can be modelled by means of finite state transition model. However, modelling the behaviour of hybrid systems like UAVs in a Kripke model is challenging. This work is aimed at capturing the behaviour of an UAV performing cooperative search mission into a Kripke model, so as to verify it against the temporal properties expressed in Computational Tree Logic (CTL. SMV model checker is used for the purpose of model checking.

  10. EBV Infection and Multiple Sclerosis : Lessons from a Marmoset Model

    NARCIS (Netherlands)

    Hart, 't Bert; Kap, Yolanda S.; Morandi, Elena; Laman, Jon D.; Gran, Bruno

    2016-01-01

    Multiple sclerosis (MS) is thought to be initiated by the interaction of genetic and environmental factors, eliciting an autoimmune attack on the central nervous system. Epstein-Barr virus (EBV) is the strongest infectious risk factor, but an explanation for the paradox between high infection preval

  11. Multiple Shape Models for Simultaneous Object Classification and Segmentation

    Science.gov (United States)

    2009-02-01

    SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18. NUMBER OF PAGES 5 19a. NAME OF RESPONSIBLE PERSON a. REPORT...prior segmentation of multiple objects with graph cuts,” in CVPR, 2008, pp. 1–8. [7] D. Cremers, T. Kohlberger , and C. Schnorr, “Shape statistics in

  12. Improved Monte Carlo model for multiple scattering calculations

    Institute of Scientific and Technical Information of China (English)

    Weiwei Cai; Lin Ma

    2012-01-01

    The coupling between the Monte Carlo (MC) method and geometrical optics to improve accuracy is investigated.The results obtained show improved agreement with previous experimental data,demonstrating that the MC method,when coupled with simple geometrical optics,can simulate multiple scattering with enhanced fidelity.

  13. Comparing Multiple Discrepancies Theory to Affective Models of Subjective Wellbeing

    Science.gov (United States)

    Blore, Jed D.; Stokes, Mark A.; Mellor, David; Firth, Lucy; Cummins, Robert A.

    2011-01-01

    The Subjective Wellbeing (SWB) literature is replete with competing theories detailing the mechanisms underlying the construction and maintenance of SWB. The current study aimed to compare and contrast two of these approaches: multiple discrepancies theory (MDT) and an affective-cognitive theory of SWB. MDT posits SWB to be the result of perceived…

  14. A Data Model for Algorithmic Multiple Criteria Decision Analysis

    NARCIS (Netherlands)

    Cailloux, O.; Tervonen, T.; Verhaegen, B.; Picalausa, F.

    2014-01-01

    Various software tools implementing multiple criteria decision analysis (MCDA) methods have appeared over the last decades. Although MCDA methods share common features, most of the implementing software have been developed independently from scratch. Majority of the tools have a proprietary storage

  15. A Data Model for Algorithmic Multiple Criteria Decision Analysis

    NARCIS (Netherlands)

    Cailloux, O.; Tervonen, T.; Verhaegen, B.; Picalausa, F.

    2014-01-01

    Various software tools implementing multiple criteria decision analysis (MCDA) methods have appeared over the last decades. Although MCDA methods share common features, most of the implementing software have been developed independently from scratch. Majority of the tools have a proprietary storage

  16. Hybrid multiple attribute decision making model based on entropy

    Institute of Scientific and Technical Information of China (English)

    Wang Wei; Cui Mingming

    2007-01-01

    From the viewpoint of entropy, this paper investigates a hybrid multiple attribute decision making problem with precision number, interval number and fuzzy number. It defines a new concept: project entropy and the decision is taken according to the values. The validity and scientific nature of the given is proven.

  17. A Convex Variational Model for Restoring Blurred Images with Multiplicative Noise

    DEFF Research Database (Denmark)

    Dong, Yiqiu; Tieyong Zeng

    2013-01-01

    In this paper, a new variational model for restoring blurred images with multiplicative noise is proposed. Based on the statistical property of the noise, a quadratic penalty function technique is utilized in order to obtain a strictly convex model under a mild condition, which guarantees...... to multiplicative noise. A comparison with other methods is provided as well....

  18. The Role of Implicit Models in Solving Verbal Problems in Multiplication and Division.

    Science.gov (United States)

    Fischbein, Efraim; And Others

    1985-01-01

    Over 600 pupils in grades five, seven, and nine in Italian schools were asked to choose the operation needed to solve 26 multiplication and division word problems. The findings seemed to confirm the impact of the repeated addition model on multiplication and of the partitive model on division. (MNS)

  19. Characterizing climate predictability and model response variability from multiple initial condition and multi-model ensembles

    CERN Document Server

    Kumar, Devashish

    2016-01-01

    Climate models are thought to solve boundary value problems unlike numerical weather prediction, which is an initial value problem. However, climate internal variability (CIV) is thought to be relatively important at near-term (0-30 year) prediction horizons, especially at higher resolutions. The recent availability of significant numbers of multi-model (MME) and multi-initial condition (MICE) ensembles allows for the first time a direct sensitivity analysis of CIV versus model response variability (MRV). Understanding the relative agreement and variability of MME and MICE ensembles for multiple regions, resolutions, and projection horizons is critical for focusing model improvements, diagnostics, and prognosis, as well as impacts, adaptation, and vulnerability studies. Here we find that CIV (MICE agreement) is lower (higher) than MRV (MME agreement) across all spatial resolutions and projection time horizons for both temperature and precipitation. However, CIV dominates MRV over higher latitudes generally an...

  20. A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle

    Science.gov (United States)

    Chockalingam, Karuppiah; Simeon, Rudo L.; Rice, Charles M.; Chen, Zhilei

    2010-01-01

    The hepatitis C virus (HCV) life cycle involves multiple steps, but most current drug candidates target only viral replication. The inability to systematically discover inhibitors targeting multiple steps of the HCV life cycle has hampered antiviral development. We present a simple screen for HCV antivirals based on the alleviation of HCV-mediated cytopathic effect in an engineered cell line—n4mBid. This approach obviates the need for a secondary screen to avoid cytotoxic false-positive hits. Application of our screen to 1280 compounds, many in clinical trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or infectious virus production by >100-fold, with one (quinidine) inhibiting infectious virus production by 450-fold relative to HCV replication levels. This approach is simple and inexpensive and should enable the rapid discovery of new classes of HCV life cycle inhibitors. PMID:20142494

  1. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.

    Directory of Open Access Journals (Sweden)

    Maria Wilbe

    2015-06-01

    Full Text Available The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H and speckled ANA (ANA(S staining pattern, and also steroid-responsive meningitis-arteritis (SRMA are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans.

  2. Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts.

    Directory of Open Access Journals (Sweden)

    Cécile Troupin

    2016-12-01

    Full Text Available The natural evolution of rabies virus (RABV provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics.

  3. Bayesian zero-failure reliability modeling and assessment method for multiple numerical control (NC) machine tools

    Institute of Scientific and Technical Information of China (English)

    阚英男; 杨兆军; 李国发; 何佳龙; 王彦鹍; 李洪洲

    2016-01-01

    A new problem that classical statistical methods are incapable of solving is reliability modeling and assessment when multiple numerical control machine tools (NCMTs) reveal zero failures after a reliability test. Thus, the zero-failure data form and corresponding Bayesian model are developed to solve the zero-failure problem of NCMTs, for which no previous suitable statistical model has been developed. An expert−judgment process that incorporates prior information is presented to solve the difficulty in obtaining reliable prior distributions of Weibull parameters. The equations for the posterior distribution of the parameter vector and the Markov chain Monte Carlo (MCMC) algorithm are derived to solve the difficulty of calculating high-dimensional integration and to obtain parameter estimators. The proposed method is applied to a real case; a corresponding programming code and trick are developed to implement an MCMC simulation in WinBUGS, and a mean time between failures (MTBF) of 1057.9 h is obtained. Given its ability to combine expert judgment, prior information, and data, the proposed reliability modeling and assessment method under the zero failure of NCMTs is validated.

  4. Binary variable multiple-model multiple imputation to address missing data mechanism uncertainty: application to a smoking cessation trial.

    Science.gov (United States)

    Siddique, Juned; Harel, Ofer; Crespi, Catherine M; Hedeker, Donald

    2014-07-30

    The true missing data mechanism is never known in practice. We present a method for generating multiple imputations for binary variables, which formally incorporates missing data mechanism uncertainty. Imputations are generated from a distribution of imputation models rather than a single model, with the distribution reflecting subjective notions of missing data mechanism uncertainty. Parameter estimates and standard errors are obtained using rules for nested multiple imputation. Using simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal smoking cessation trial where nonignorably missing data were a concern. Our method provides a simple approach for formalizing subjective notions regarding nonresponse and can be implemented using existing imputation software.

  5. Addressing Missing Data Mechanism Uncertainty using Multiple-Model Multiple Imputation: Application to a Longitudinal Clinical Trial.

    Science.gov (United States)

    Siddique, Juned; Harel, Ofer; Crespi, Catherine M

    2012-12-01

    We present a framework for generating multiple imputations for continuous data when the missing data mechanism is unknown. Imputations are generated from more than one imputation model in order to incorporate uncertainty regarding the missing data mechanism. Parameter estimates based on the different imputation models are combined using rules for nested multiple imputation. Through the use of simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal clinical trial of low-income women with depression where nonignorably missing data were a concern. We show that different assumptions regarding the missing data mechanism can have a substantial impact on inferences. Our method provides a simple approach for formalizing subjective notions regarding nonresponse so that they can be easily stated, communicated, and compared.

  6. Extending positive C-LASS results across multiple instructors and multiple classes of Modeling Instruction

    CERN Document Server

    Brewe, Eric; de la Garza, Jorge; Kramer, Laird H

    2013-01-01

    We report on a multi year study of student attitudes measured with the Colorado Learning Attitudes about Science Survey (C-LASS) in calculus-based introductory physics taught with the Modeling Instruction curriculum. We find that five of six instructors and eight of nine sections using Modeling Instruction showed improved attitudes from pre to post course. Cohen's d effect sizes range from 0.08 to 0.95 for individual instructors. The average effect was d = 0.45, with a 95% confidence interval of (0.26 to 0.64). These results build on previously published results showing positive shifts in attitudes from Modeling Instruction classes. We interpret these data in light of other published positive attitudinal shifts and explore mechanistic explanations for similarities and differences with other published positive shifts.

  7. Collaborative product and process model: Multiple Viewpoints approach

    CERN Document Server

    Geryville, Hichem; Ouzrout, Yacine; Sapidis, Nikolaos

    2007-01-01

    The design and development of complex products invariably involves many actors who have different points of view on the problem they are addressing, the product being developed, and the process by which it is being developed. The actors' viewpoints approach was designed to provide an organisational framework in which these different perspectives or points of views, and their relationships, could be explicitly gathered and formatted (by actor activity's focus). The approach acknowledges the inevitability of multiple interpretation of product information as different views, promotes gathering of actors' interests, and encourages retrieved adequate information while providing support for integration through PLM and/or SCM collaboration. In this paper, we present our multiple viewpoints approach, and we illustrate it by an industrial example on cyclone vessel product.

  8. NOTE: Modelling multiple laser pulses for port wine stain treatment

    Science.gov (United States)

    Verkruysse, Wim; van Gemert, Martin J. C.; Smithies, Derek J.; Nelson, J. Stuart

    2000-12-01

    Many port wine stains (PWS) are still resistant to pulsed dye laser treatment. However, anecdotal information suggests that multiple-pulse laser irradiation improves patient outcome. Our aims in this note are to explain the underlying mechanism and estimate the possible thermal effects of multiple pulses in vascular structures typical of PWS. Based on linear response theory, the linear combination of two thermal contributions is responsible for the total increase in temperature in laser irradiated blood vessels: direct light absorption by blood and direct bilateral thermal heat conduction from adjacent blood vessels. The latter contribution to the increase in temperature in the targeted vessel can be significant, particularly if some adjacent vessels are in close proximity, such as in cases of optical shielding of the targeted vessel, or if the vessels are relatively distant but many in number. We present evidence that multiple-pulse laser irradiation targets blood vessels that are optically shielded by other vessels. Therefore, it may be a means of enhancing PWS therapy for lesions that fail to respond to single-pulse dye laser treatment.

  9. Atomic force microscopy measurements reveal multiple bonds between Helicobacter pylori blood group antigen binding adhesin and Lewis b ligand.

    Science.gov (United States)

    Parreira, P; Shi, Q; Magalhaes, A; Reis, C A; Bugaytsova, J; Borén, T; Leckband, D; Martins, M C L

    2014-12-01

    The strength of binding between the Helicobacter pylori blood group antigen-binding adhesin (BabA) and its cognate glycan receptor, the Lewis b blood group antigen (Le(b)), was measured by means of atomic force microscopy. High-resolution measurements of rupture forces between single receptor-ligand pairs were performed between the purified BabA and immobilized Le(b) structures on self-assembled monolayers. Dynamic force spectroscopy revealed two similar but statistically different bond populations. These findings suggest that the BabA may form different adhesive attachments to the gastric mucosa in ways that enhance the efficiency and stability of bacterial adhesion.

  10. Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication.

    Directory of Open Access Journals (Sweden)

    Subhash C Verma

    2011-11-01

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV, an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA. Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD. Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA

  11. LUT REVEALS AN ALGOL-TYPE ECLIPSING BINARY WITH THREE ADDITIONAL STELLAR COMPANIONS IN A MULTIPLE SYSTEM

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, L.-Y.; Zhou, X.; Qian, S.-B.; Li, L.-J.; Liao, W.-P.; Tian, X.-M.; Wang, Z.-H. [Yunnan Observatories, Chinese Academy of Sciences (CAS), P.O. Box 110, 650011 Kunming (China); Hu, J.-Y., E-mail: zhuly@ynao.ac.cn [National Astronomical Observatories, Chinese Academy of Sciences, 100012 Beijing (China)

    2016-04-15

    A complete light curve of the neglected eclipsing binary Algol V548 Cygni in the UV band was obtained with the Lunar-based Ultraviolet Telescope in 2014 May. Photometric solutions are obtained using the Wilson–Devinney method. It is found that solutions with and without third light are quite different. The mass ratio without third light is determined to be q = 0.307, while that derived with third light is q = 0.606. It is shown that V548 Cygni is a semi-detached binary where the secondary component is filling the critical Roche lobe. An analysis of all available eclipse times suggests that there are three cyclic variations in the O–C diagram that are interpreted by the light travel-time effect via the presence of three additional stellar companions. This is in agreement with the presence of a large quantity of third light in the system. The masses of these companions are estimated as m sin i′ ∼ 1.09, 0.20, and 0.52 M{sub ⊙}. They are orbiting the central binary with orbital periods of about 5.5, 23.3, and 69.9 years, i.e., in 1:4:12 resonance orbit. Their orbital separations are about 4.5, 13.2, and 26.4 au, respectively. Our photometric solutions suggest that they contribute about 32.4% to the total light of the multiple system. No obvious long-term changes in the orbital period were found, indicating that the contributions of the mass transfer and the mass loss due to magnetic braking to the period variations are comparable. The detection of three possible additional stellar components orbiting a typical Algol in a multiple system make V548 Cygni a very interesting binary to study in the future.

  12. Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

    Science.gov (United States)

    Guaitoli, Giambattista; Raimondi, Francesco; Gilsbach, Bernd K.; Gómez-Llorente, Yacob; Deyaert, Egon; Renzi, Fabiana; Li, Xianting; Schaffner, Adam; Jagtap, Pravin Kumar Ankush; Boldt, Karsten; von Zweydorf, Felix; Gotthardt, Katja; Lorimer, Donald D.; Yue, Zhenyu; Burgin, Alex; Janjic, Nebojsa; Sattler, Michael; Versées, Wim; Ueffing, Marius; Ubarretxena-Belandia, Iban; Kortholt, Arjan; Gloeckner, Christian Johannes

    2016-01-01

    Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson’s disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity—together with the LRR domain—to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD. PMID:27357661

  13. Multiple Damage Progression Paths in Model-based Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Model-based prognostics approaches employ do- main knowledge about a system, its components, and how they fail through the use of physics-based models. Compo- nent...

  14. Asymptotic properties of maximum likelihood estimators in models with multiple change points

    CERN Document Server

    He, Heping; 10.3150/09-BEJ232

    2011-01-01

    Models with multiple change points are used in many fields; however, the theoretical properties of maximum likelihood estimators of such models have received relatively little attention. The goal of this paper is to establish the asymptotic properties of maximum likelihood estimators of the parameters of a multiple change-point model for a general class of models in which the form of the distribution can change from segment to segment and in which, possibly, there are parameters that are common to all segments. Consistency of the maximum likelihood estimators of the change points is established and the rate of convergence is determined; the asymptotic distribution of the maximum likelihood estimators of the parameters of the within-segment distributions is also derived. Since the approach used in single change-point models is not easily extended to multiple change-point models, these results require the introduction of those tools for analyzing the likelihood function in a multiple change-point model.

  15. Enhancing multiple-point geostatistical modeling: 2. Iterative simulation and multiple distance function

    Science.gov (United States)

    Tahmasebi, Pejman; Sahimi, Muhammad

    2016-03-01

    This series addresses a fundamental issue in multiple-point statistical (MPS) simulation for generation of realizations of large-scale porous media. Past methods suffer from the fact that they generate discontinuities and patchiness in the realizations that, in turn, affect their flow and transport properties. Part I of this series addressed certain aspects of this fundamental issue, and proposed two ways of improving of one such MPS method, namely, the cross correlation-based simulation (CCSIM) method that was proposed by the authors. In the present paper, a new algorithm is proposed to further improve the quality of the realizations. The method utilizes the realizations generated by the algorithm introduced in Part I, iteratively removes any possible remaining discontinuities in them, and addresses the problem with honoring hard (quantitative) data, using an error map. The map represents the differences between the patterns in the training image (TI) and the current iteration of a realization. The resulting iterative CCSIM—the iCCSIM algorithm—utilizes a random path and the error map to identify the locations in the current realization in the iteration process that need further "repairing;" that is, those locations at which discontinuities may still exist. The computational time of the new iterative algorithm is considerably lower than one in which every cell of the simulation grid is visited in order to repair the discontinuities. Furthermore, several efficient distance functions are introduced by which one extracts effectively key information from the TIs. To increase the quality of the realizations and extracting the maximum amount of information from the TIs, the distance functions can be used simultaneously. The performance of the iCCSIM algorithm is studied using very complex 2-D and 3-D examples, including those that are process-based. Comparison is made between the quality and accuracy of the results with those generated by the original CCSIM

  16. DESIGNING A FORECAST MODEL FOR ECONOMIC GROWTH OF JAPAN USING COMPETITIVE (HYBRID ANN VS MULTIPLE REGRESSION MODELS

    Directory of Open Access Journals (Sweden)

    Ahmet DEMIR

    2015-07-01

    Full Text Available Artificial neural network models have been already used on many different fields successfully. However, many researches show that ANN models provide better optimum results than other competitive models in most of the researches. But does it provide optimum solutions in case ANN is proposed as hybrid model? The answer of this question is given in this research by using these models on modelling a forecast for GDP growth of Japan. Multiple regression models utilized as competitive models versus hybrid ANN (ANN + multiple regression models. Results have shown that hybrid model gives better responds than multiple regression models. However, variables, which were significantly affecting GDP growth, were determined and some of the variables, which were assumed to be affecting GDP growth of Japan, were eliminated statistically.

  17. A Review of the Modelling of Thermally Interacting Multiple Boreholes

    Directory of Open Access Journals (Sweden)

    Seama Koohi-Fayegh

    2013-06-01

    Full Text Available Much attention is now focused on utilizing ground heat pumps for heating and cooling buildings, as well as water heating, refrigeration and other thermal tasks. Modeling such systems is important for understanding, designing and optimizing their performance and characteristics. Several heat transfer models exist for ground heat exchangers. In this review article, challenges of modelling heat transfer in vertical heat exchangers are described, some analytical and numerical models are reviewed and compared, recent related developments are described and the importance of modelling these systems is discussed from a variety of aspects, such as sustainability of geothermal systems or their potential impacts on the ecosystems nearby.

  18. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben; Scheike, Thomas H.

    2016-01-01

    mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline....... For the suggested model, some covariate effects are allowed to be time-varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness...... of fit test that is asymptotically justified. The proposed methodology is evaluated via simulation studies and further applied to a kidney cancer data set collected from a clinical trial....

  19. Numerical modelling of multiple scattering between two elastical particles

    DEFF Research Database (Denmark)

    Bjørnø, Irina; Jensen, Leif Bjørnø

    1998-01-01

    in suspension have been studied extensively since Foldy's formulation of his theory for isotropic scattering by randomly distributed scatterers. However, a number of important problems related to multiple scattering are still far from finding their solutions. A particular, but still unsolved, problem...... is higher than 20 g/l of sand particles. This paper reports an attempt to illuminate and to solve the proximity threshold question, by an in-depth numerical study of the interaction of ultrasonic signals with two canonically shaped elastic particles. Introductory experimental results seem to create evidence...

  20. Joint Modeling of Multiple Crimes: A Bayesian Spatial Approach

    Directory of Open Access Journals (Sweden)

    Hongqiang Liu

    2017-01-01

    Full Text Available A multivariate Bayesian spatial modeling approach was used to jointly model the counts of two types of crime, i.e., burglary and non-motor vehicle theft, and explore the geographic pattern of crime risks and relevant risk factors. In contrast to the univariate model, which assumes independence across outcomes, the multivariate approach takes into account potential correlations between crimes. Six independent variables are included in the model as potential risk factors. In order to fully present this method, both the multivariate model and its univariate counterpart are examined. We fitted the two models to the data and assessed them using the deviance information criterion. A comparison of the results from the two models indicates that the multivariate model was superior to the univariate model. Our results show that population density and bar density are clearly associated with both burglary and non-motor vehicle theft risks and indicate a close relationship between these two types of crime. The posterior means and 2.5% percentile of type-specific crime risks estimated by the multivariate model were mapped to uncover the geographic patterns. The implications, limitations and future work of the study are discussed in the concluding section.

  1. Calibration of Predictor Models Using Multiple Validation Experiments

    Science.gov (United States)

    Crespo, Luis G.; Kenny, Sean P.; Giesy, Daniel P.

    2015-01-01

    This paper presents a framework for calibrating computational models using data from several and possibly dissimilar validation experiments. The offset between model predictions and observations, which might be caused by measurement noise, model-form uncertainty, and numerical error, drives the process by which uncertainty in the models parameters is characterized. The resulting description of uncertainty along with the computational model constitute a predictor model. Two types of predictor models are studied: Interval Predictor Models (IPMs) and Random Predictor Models (RPMs). IPMs use sets to characterize uncertainty, whereas RPMs use random vectors. The propagation of a set through a model makes the response an interval valued function of the state, whereas the propagation of a random vector yields a random process. Optimization-based strategies for calculating both types of predictor models are proposed. Whereas the formulations used to calculate IPMs target solutions leading to the interval value function of minimal spread containing all observations, those for RPMs seek to maximize the models' ability to reproduce the distribution of observations. Regarding RPMs, we choose a structure for the random vector (i.e., the assignment of probability to points in the parameter space) solely dependent on the prediction error. As such, the probabilistic description of uncertainty is not a subjective assignment of belief, nor is it expected to asymptotically converge to a fixed value, but instead it casts the model's ability to reproduce the experimental data. This framework enables evaluating the spread and distribution of the predicted response of target applications depending on the same parameters beyond the validation domain.

  2. A SNP based linkage map of the turkey genome reveals multiple intrachromosomal rearrangements between the Turkey and Chicken genomes

    Directory of Open Access Journals (Sweden)

    Vereijken Addie

    2010-11-01

    Full Text Available Abstract Background The turkey (Meleagris gallopavo is an important agricultural species that is the second largest contributor to the world's poultry meat production. The genomic resources of turkey provide turkey breeders with tools needed for the genetic improvement of commercial breeds of turkey for economically important traits. A linkage map of turkey is essential not only for the mapping of quantitative trait loci, but also as a framework to enable the assignment of sequence contigs to specific chromosomes. Comparative genomics with chicken provides insight into mechanisms of genome evolution and helps in identifying rare genomic events such as genomic rearrangements and duplications/deletions. Results Eighteen full sib families, comprising 1008 (35 F1 and 973 F2 birds, were genotyped for 775 single nucleotide polymorphisms (SNPs. Of the 775 SNPs, 570 were informative and used to construct a linkage map in turkey. The final map contains 531 markers in 28 linkage groups. The total genetic distance covered by these linkage groups is 2,324 centimorgans (cM with the largest linkage group (81 loci measuring 326 cM. Average marker interval for all markers across the 28 linkage groups is 4.6 cM. Comparative mapping of turkey and chicken revealed two inter-, and 57 intrachromosomal rearrangements between these two species. Conclusion Our turkey genetic map of 531 markers reveals a genome length of 2,324 cM. Our linkage map provides an improvement of previously published maps because of the more even distribution of the markers and because the map is completely based on SNP markers enabling easier and faster genotyping assays than the microsatellitemarkers used in previous linkage maps. Turkey and chicken are shown to have a highly conserved genomic structure with a relatively low number of inter-, and intrachromosomal rearrangements.

  3. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Science.gov (United States)

    Anderson, Jennifer L; Rodríguez Marí, Adriana; Braasch, Ingo; Amores, Angel; Hohenlohe, Paul; Batzel, Peter; Postlethwait, John H

    2012-01-01

    Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio), neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate), the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2) offspring of reciprocal crosses between Oregon *AB and Nadia (NA) wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag) markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  4. Transcriptome and proteomic analyses reveal multiple differences associated with chloroplast development in the spaceflight-induced wheat albino mutant mta.

    Science.gov (United States)

    Shi, Kui; Gu, Jiayu; Guo, Huijun; Zhao, Linshu; Xie, Yongdun; Xiong, Hongchun; Li, Junhui; Zhao, Shirong; Song, Xiyun; Liu, Luxiang

    2017-01-01

    Chloroplast development is an integral part of plant survival and growth, and occurs in parallel with chlorophyll biosynthesis. However, little is known about the mechanisms underlying chloroplast development in hexaploid wheat. Here, we obtained a spaceflight-induced wheat albino mutant mta. Chloroplast ultra-structural observation showed that chloroplasts of mta exhibit abnormal morphology and distribution compared to wild type. Photosynthetic pigments content was also significantly decreased in mta. Transcriptome and chloroplast proteome profiling of mta and wild type were done to identify differentially expressed genes (DEGs) and proteins (DEPs), respectively. In total 4,588 DEGs including 1,980 up- and 2,608 down-regulated, and 48 chloroplast DEPs including 15 up- and 33 down-regulated were identified in mta. Classification of DEGs revealed that most were involved in chloroplast development, chlorophyll biosynthesis, or photosynthesis. Besides, transcription factors such as PIF3, GLK and MYB which might participate in those pathways were also identified. The correlation analysis between DEGs and DEPs revealed that the transcript-to-protein in abundance was functioned into photosynthesis and chloroplast relevant groups. Real time qPCR analysis validated that the expression level of genes encoding photosynthetic proteins was significantly decreased in mta. Together, our results suggest that the molecular mechanism for albino leaf color formation in mta is a thoroughly regulated and complicated process. The combined analysis of transcriptome and proteome afford comprehensive information for further research on chloroplast development mechanism in wheat. And spaceflight provides a potential means for mutagenesis in crop breeding.

  5. The Distribution of Thermophilic Sulfate-reducing Bacteria Along an Estuarine Gradient Reveals Multiple Origins of Endospores in Estuarine Sediments

    Science.gov (United States)

    Bell, E.

    2015-12-01

    Cold marine sediments harbour inactive spores of thermophilic bacteria. These misplaced thermophiles are genetically similar to microorganisms detected in deep biosphere environments, leading to the hypothesis that seabed fluid flow transports thermophiles out of warm subsurface environments and into the ocean. Estuaries form the transition between the marine and the terrestrial biosphere and are influenced by tidal currents, surface run-off and groundwater seepage. Endospores from thermophilic bacteria present in estuarine sediments could therefore originate from a number of sources that may influence the estuary differently. We have therefore tested the hypothesis that this will lead to a gradient in the composition of thermophilic endospore populations in estuarine sediments. The distribution of thermophilic spore-forming sulfate-reducing bacteria along an estuarine gradient from freshwater (River Tyne, UK) to marine (North Sea) was investigated. Microbial community analysis by 16S rRNA gene amplicon sequencing revealed changes in the thermophilic population enriched at different locations within the estuary. Certain species were only detected at the marine end, highlighting possible links to deep marine biosphere habitats such as oil reservoirs that harbour closely related Desulfotomaculum spp. Conversely, other taxa were predominantly observed in the freshwater reaches of the estuary indicating dispersal from an upstream or terrestrial source. Different endospore populations were enriched dependent on incubation temperature and spore heat-resistance. Microcosms incubated at 50, 60 or 70°C showed a shift in the dominant species of Desulfotomaculum enriched as the temperature increased. Microcosms triple-autoclaved at 121°C prior to incubation still showed rapid and reproducible sulfate-reduction and some Desulfotomaculum spp. remained active after autoclaving at 130°C. These results show that temperature physiology and biogeographic patterns can be used to

  6. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    Full Text Available Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio, neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate, the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  7. Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

    Science.gov (United States)

    Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F.; Sadoshima, Junichi; Tian, Bin

    2011-01-01

    Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842

  8. Comparative analyses of lipidomes and transcriptomes reveal a concerted action of multiple defensive systems against photooxidative stress in Haematococcus pluvialis.

    Science.gov (United States)

    Gwak, Yunho; Hwang, Yong-sic; Wang, Baobei; Kim, Minju; Jeong, Jooyeon; Lee, Choul-Gyun; Hu, Qiang; Han, Danxiang; Jin, EonSeon

    2014-08-01

    Haematococcus pluvialis cells predominantly remain in the macrozooid stage under favourable environmental conditions but are rapidly differentiated into haematocysts upon exposure to various environmental stresses. Haematocysts are characterized by massive accumulations of astaxanthin sequestered in cytosolic oil globules. Lipidomic analyses revealed that synthesis of the storage lipid triacylglycerol (TAG) was substantially stimulated under high irradiance. Simultaneously, remodelling of membrane glycerolipids occurred as a result of dramatic reductions in chloroplast membrane glycolipids but remained unchanged or declined slightly in extraplastidic membrane glycerolipids. De novo assembly of transcriptomes revealed the genomic and metabolic features of this unsequenced microalga. Comparative transcriptomic analysis showed that so-called resting cells (haematocysts) may be more active than fast-growing vegetative cells (macrozooids) regarding metabolic pathways and functions. Comparative transcriptomic analyses of astaxanthin biosynthesis suggested that the non-mevalonate pathway mediated the synthesis of isopentenyl diphosphate, as the majority of genes involved in subsequent astaxanthin biosynthesis were substantially up-regulated under high irradiance, with the genes encoding phytoene synthase, phytoene desaturase, and β-carotene hydroxylase identified as the most prominent regulatory components. Accumulation of TAG under high irradiance was attributed to moderate up-regulation of de novo fatty acid biosynthesis at the gene level as well as to moderate elevation of the TAG assembly pathways. Additionally, inferred from transcriptomic differentiation, an increase in reactive oxygen species (ROS) scavenging activity, a decrease in ROS production, and the relaxation of over-reduction of the photosynthetic electron transport chain will work together to protect against photooxidative stress in H. pluvialis under high irradiance. © The Author 2014. Published by

  9. Multilocus sequence analyses reveal extensive diversity and multiple origins of fluconazole resistance in Candida tropicalis from tropical China

    Science.gov (United States)

    Wu, Jin-Yan; Guo, Hong; Wang, Hua-Min; Yi, Guo-Hui; Zhou, Li-Min; He, Xiao-Wen; Zhang, Ying; Xu, Jianping

    2017-01-01

    Candida tropicalis is among the most prevalent human pathogenic yeast species, second only to C. albicans in certain geographic regions such as East Asia and Brazil. However, compared to C. albicans, relatively little is known about the patterns of genetic variation in C. tropicalis. This study analyzed the genetic diversity and relationships among isolates of C. tropicalis from the southern Chinese island of Hainan. A total of 116 isolates were obtained from seven geographic regions located across the Island. For each isolate, a total of 2677 bp from six gene loci were sequenced and 79 (2.96%) polymorphic nucleotide sites were found in our sample. Comparisons with strains reported from other parts of the world identified significant novel diversities in Hainan, including an average of six novel sequences (with a range 1 to 14) per locus and 80 novel diploid sequence types. Most of the genetic variation was found within individual strains and there was abundant evidence for gene flow among the seven geographic locations within Hainan. Interestingly, our analyses identified no significant correlation between the diploid sequence types at the six loci and fluconazole susceptibility, consistent with multiple origins of fluconazole resistance in the Hainan population of C. tropicalis. PMID:28186162

  10. A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

  11. Arabidopsis lonely guy (LOG) multiple mutants reveal a central role of the LOG-dependent pathway in cytokinin activation.

    Science.gov (United States)

    Tokunaga, Hiroki; Kojima, Mikiko; Kuroha, Takeshi; Ishida, Takashi; Sugimoto, Keiko; Kiba, Takatoshi; Sakakibara, Hitoshi

    2012-01-01

    Cytokinins are phytohormones that play key roles in the maintenance of stem cell activity in plants. Although alternative single-step and two-step activation pathways for cytokinin have been proposed, the significance of the single-step pathway which is catalyzed by LONELY GUY (LOG), is not fully understood. We analyzed the metabolic flow of cytokinin activation in Arabidopsis log multiple mutants using stable isotope-labeled tracers and characterized the mutants' morphological and developmental phenotypes. In tracer experiments, cytokinin activation was inhibited most pronouncedly by log7, while the other log mutations had cumulative effects. Although sextuple or lower-order mutants did not show drastic phenotypes in vegetative growth, the log1log2log3log4log5log7log8 septuple T-DNA insertion mutant in which the LOG-dependent pathway is impaired, displayed severe retardation of shoot and root growth with defects in the maintenance of the apical meristems. Detailed observation of the mutants showed that LOG7 was required for the maintenance of shoot apical meristem size. LOG7 was also suggested to play a role for normal primary root growth together with LOG3 and LOG4. These results suggest a dominant role of the single-step activation pathway mediated by LOGs for cytokinin production, and overlapping but differentiated functions of the members of the LOG gene family in growth and development.

  12. Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations.

    Science.gov (United States)

    Wang, Beibei; Weng, Jingwei; Wang, Wenning

    2014-09-01

    Outer membrane protein TolC serves as an exit duct for exporting substances out of cell. The occluded periplasmic entrance of TolC is required to open for substrate transport, although the opening mechanism remains elusive. In this study, systematic molecular dynamics (MD) simulations for wild type TolC and six mutants were performed to explore the conformational dynamics of TolC. The periplasmic gate was shown to sample multiple conformational states with various degrees of gating opening. The gate opening was facilitated by all mutations except Y362F, which adopts an even more closed state than wild type TolC. The interprotomer salt-bridge R367-D153 is turned out to be crucial for periplasmic gate opening. The mutations that disrupt the interactions at the periplasmic tip may affect the stability of the trimeric assembly of TolC. Structural asymmetry of the periplasmic gate was observed to be opening size dependent. Asymmetric conformations are found in moderately opening states, while the most and the least opening states are often more symmetric. Finally, it is shown that lowering pH can remarkably stabilize the closed state of the periplasmic gate.

  13. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Directory of Open Access Journals (Sweden)

    Trevor P. Fidler

    2017-07-01

    Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

  14. Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; Gaffrey, Matthew J.; Hu, Dehong; Szymanski, Craig J.; Xie, Yumei; Melby, Eric S.; Dohnalkova, Alice; Taylor, Ronald C.; Grate, Eva K.; Cooley, Scott K.; McDermott, Jason E.; Heredia-Langner, Alejandro; Orr, Galya

    2016-11-22

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with upregulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly downregulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong upregulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis and organelle activities. In contrast, strategies unique to carboxylated QDs showed upregulation of DNA repair and RNA activities, and decreased regulation of cell division, coupled in some cases with upregulation of stress responses and ATP related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified, proactive defenses or repairs of the NP insults.

  15. A comprehensive molecular phylogeny of dalytyphloplanida (platyhelminthes: rhabdocoela) reveals multiple escapes from the marine environment and origins of symbiotic relationships.

    Science.gov (United States)

    Van Steenkiste, Niels; Tessens, Bart; Willems, Wim; Backeljau, Thierry; Jondelius, Ulf; Artois, Tom

    2013-01-01

    In this study we elaborate the phylogeny of Dalytyphloplanida based on complete 18S rDNA (156 sequences) and partial 28S rDNA (125 sequences), using a Maximum Likelihood and a Bayesian Inference approach, in order to investigate the origin of a limnic or limnoterrestrial and of a symbiotic lifestyle in this large group of rhabditophoran flatworms. The results of our phylogenetic analyses and ancestral state reconstructions indicate that dalytyphloplanids have their origin in the marine environment and that there was one highly successful invasion of the freshwater environment, leading to a large radiation of limnic and limnoterrestrial dalytyphloplanids. This monophyletic freshwater clade, Limnotyphloplanida, comprises the taxa Dalyelliidae, Temnocephalida, and most Typhloplanidae. Temnocephalida can be considered ectosymbiotic Dalyelliidae as they are embedded within this group. Secondary returns to brackish water and marine environments occurred relatively frequently in several dalyeliid and typhloplanid taxa. Our phylogenies also show that, apart from the Limnotyphloplanida, there have been only few independent invasions of the limnic environment, and apparently these were not followed by spectacular speciation events. The distinct phylogenetic positions of the symbiotic taxa also suggest multiple origins of commensal and parasitic life strategies within Dalytyphloplanida. The previously established higher-level dalytyphloplanid clades are confirmed in our topologies, but many of the traditional families are not monophyletic. Alternative hypothesis testing constraining the monophyly of these families in the topologies and using the approximately unbiased test, also statistically rejects their monophyly.

  16. SET7/9 Catalytic Mutants Reveal the Role of Active Site Water Molecules in Lysine Multiple Methylation

    Energy Technology Data Exchange (ETDEWEB)

    Del Rizzo, Paul A.; Couture, Jean-François; Dirk, Lynnette M.A.; Strunk, Bethany S.; Roiko, Marijo S.; Brunzelle, Joseph S.; Houtz, Robert L.; Trievel, Raymond C. (Michigan); (NWU); (Kentucky)

    2010-11-15

    SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine {epsilon}-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine {epsilon}-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated {epsilon}-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes.

  17. Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) Reveals Multiple Protease-Like Transcripts.

    Science.gov (United States)

    Valencia, Arnubio; Wang, Haichuan; Soto, Alberto; Aristizabal, Manuel; Arboleda, Jorge W; Eyun, Seong-Il; Noriega, Daniel D; Siegfried, Blair

    2016-01-01

    The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest.

  18. Large-scale phylogenetic analyses reveal multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms associated with climate change.

    Science.gov (United States)

    Li, Hong-Lei; Wang, Wei; Mortimer, Peter E; Li, Rui-Qi; Li, De-Zhu; Hyde, Kevin D; Xu, Jian-Chu; Soltis, Douglas E; Chen, Zhi-Duan

    2015-09-10

    Nitrogen is fundamental to all life forms and is also one of the most limiting of nutrients for plant growth. Several clades of angiosperms have developed symbiotic relationships with actinorhizal bacteria that fix atmospheric nitrogen and increase access to this nutrient. However, the evolutionary patterns of actinorhizal nitrogen-fixing symbioses remain unclear to date. Furthermore the underlying environmental pressures that led to the gain of symbiotic actinorhizal nitrogen fixation have never been investigated. Here, we present the most comprehensive genus-level phylogenetic analysis of the nitrogen-fixing angiosperms based on three plastid loci. We found that actinorhizal nitrogen-fixing species are distributed in nine distinct lineages. By dating the branching events, we determined that seven actinorhizal nitrogen-fixing lineages originated during the Late Cretaceous, and two more emerged during the Eocene. We put forward a hypothesis that multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms may have been associated with increased global temperatures and high levels of atmospheric carbon dioxide during these two time periods, as well as the availability of open habitats with high light conditions. Our nearly complete genus-level time-tree for the nitrogen-fixing clade is a significant advance in understanding the evolutionary and ecological background of this important symbiosis between plants and bacteria.

  19. Analysis of the outer membrane proteome and secretome of Bacteroides fragilis reveals a multiplicity of secretion mechanisms.

    Directory of Open Access Journals (Sweden)

    Marlena M Wilson

    Full Text Available Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes.

  20. Multiple causation of phylogeographical pattern as revealed by nested clade analysis of the bamboo viper (Trimeresurus stejnegeri) within Taiwan.

    Science.gov (United States)

    Creer, S; Malhotra, A; Thorpe, R S; Chou, W H

    2001-08-01

    In order to assess the utility of nested clade analysis, both standard phylogenetic algorithms and nested clade analysis were performed on a geographically widespread survey of mitochondrial DNA haplotypes of the bamboo viper, Trimeresurus stejnegeri, within Taiwan. Gross tree topologies were congruent for all analyses and indicated the presence of two geographically overlapping clades within Taiwan. The smaller lineage was restricted to the north and east coasts, whereas the larger lineage occupied all but the northern range of the species within Taiwan including the Pacific offshore populations of Green and Orchid Islands. The phylogeographical pattern supports the existence of at least one colonization event from the continent since the initial isolation of Taiwan from the mainland in the Pliocene. However, determining the exact number of colonization events was not possible due to the simultaneous vicariant forces of hypothesized continental landbridge connections and the occurrence of dramatic in situ orogenesis throughout the Pleistocene. Nested clade analysis provided multiple temporal and spatial population historical inferences that are not possible with standard analyses and therefore should become widely applied to future phylogeographical studies.

  1. Analyses of transcriptome sequences reveal multiple ancient large-scale duplication events in the ancestor of Sphagnopsida (Bryophyta).

    Science.gov (United States)

    Devos, Nicolas; Szövényi, Péter; Weston, David J; Rothfels, Carl J; Johnson, Matthew G; Shaw, A Jonathan

    2016-07-01

    The goal of this research was to investigate whether there has been a whole-genome duplication (WGD) in the ancestry of Sphagnum (peatmoss) or the class Sphagnopsida, and to determine if the timing of any such duplication(s) and patterns of paralog retention could help explain the rapid radiation and current ecological dominance of peatmosses. RNA sequencing (RNA-seq) data were generated for nine taxa in Sphagnopsida (Bryophyta). Analyses of frequency plots for synonymous substitutions per synonymous site (Ks ) between paralogous gene pairs and reconciliation of 578 gene trees were conducted to assess evidence of large-scale or genome-wide duplication events in each transcriptome. Both Ks frequency plots and gene tree-based analyses indicate multiple duplication events in the history of the Sphagnopsida. The most recent WGD event predates divergence of Sphagnum from the two other genera of Sphagnopsida. Duplicate retention is highly variable across species, which might be best explained by local adaptation. Our analyses indicate that the last WGD could have been an important factor underlying the diversification of peatmosses and facilitated their rise to ecological dominance in peatlands. The timing of the duplication events and their significance in the evolutionary history of peat mosses are discussed.

  2. Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar (Coleoptera: Curculionidae Reveals Multiple Protease-Like Transcripts.

    Directory of Open Access Journals (Sweden)

    Arnubio Valencia

    Full Text Available The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest.

  3. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    Science.gov (United States)

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide Pgenetically tractable and provide insight into the genetic architecture of complex traits.

  4. A comprehensive molecular phylogeny of dalytyphloplanida (platyhelminthes: rhabdocoela reveals multiple escapes from the marine environment and origins of symbiotic relationships.

    Directory of Open Access Journals (Sweden)

    Niels Van Steenkiste

    Full Text Available In this study we elaborate the phylogeny of Dalytyphloplanida based on complete 18S rDNA (156 sequences and partial 28S rDNA (125 sequences, using a Maximum Likelihood and a Bayesian Inference approach, in order to investigate the origin of a limnic or limnoterrestrial and of a symbiotic lifestyle in this large group of rhabditophoran flatworms. The results of our phylogenetic analyses and ancestral state reconstructions indicate that dalytyphloplanids have their origin in the marine environment and that there was one highly successful invasion of the freshwater environment, leading to a large radiation of limnic and limnoterrestrial dalytyphloplanids. This monophyletic freshwater clade, Limnotyphloplanida, comprises the taxa Dalyelliidae, Temnocephalida, and most Typhloplanidae. Temnocephalida can be considered ectosymbiotic Dalyelliidae as they are embedded within this group. Secondary returns to brackish water and marine environments occurred relatively frequently in several dalyeliid and typhloplanid taxa. Our phylogenies also show that, apart from the Limnotyphloplanida, there have been only few independent invasions of the limnic environment, and apparently these were not followed by spectacular speciation events. The distinct phylogenetic positions of the symbiotic taxa also suggest multiple origins of commensal and parasitic life strategies within Dalytyphloplanida. The previously established higher-level dalytyphloplanid clades are confirmed in our topologies, but many of the traditional families are not monophyletic. Alternative hypothesis testing constraining the monophyly of these families in the topologies and using the approximately unbiased test, also statistically rejects their monophyly.

  5. A Delay Model of Multiple-Valued Logic Circuits Consisting of Min, Max, and Literal Operations

    Science.gov (United States)

    Takagi, Noboru

    Delay models for binary logic circuits have been proposed and clarified their mathematical properties. Kleene's ternary logic is one of the simplest delay models to express transient behavior of binary logic circuits. Goto first applied Kleene's ternary logic to hazard detection of binary logic circuits in 1948. Besides Kleene's ternary logic, there are many delay models of binary logic circuits, Lewis's 5-valued logic etc. On the other hand, multiple-valued logic circuits recently play an important role for realizing digital circuits. This is because, for example, they can reduce the size of a chip dramatically. Though multiple-valued logic circuits become more important, there are few discussions on delay models of multiple-valued logic circuits. Then, in this paper, we introduce a delay model of multiple-valued logic circuits, which are constructed by Min, Max, and Literal operations. We then show some of the mathematical properties of our delay model.

  6. Finding all multiple stable fixpoints of n-species Lotka-Volterra competition models.

    Science.gov (United States)

    Lischke, Heike; Löffler, Thomas J

    2017-06-01

    One way to explore assembly of extant and novel communities from species pools, and by that biodiversity and species ranges, is to study the equilibrium behavior of dynamic competition models such as the Lotka-Volterra competition (LVC) model. We present a novel method (COMMUSTIX) to determine all stable fixpoints of the general LVC model with abundances x from a given pool of n species. To that purpose, we split the species in potentially surviving species (xi>0) and in others going extinct (xi=0). We derived criteria for the stability of xi=0 and for the equilibrium of xi>0 to determine possible combinations of extinct and surviving species by iteratively applying a mixed binary linear optimization algorithm. We tested this new method against (a) the numerical solution at equilibrium of the LVC ordinary differential equations (ODEs) and (b) the fixpoints of all combinations of surviving and extinct species (possible only for small n), tested for stability and non-negativity. The tests revealed that COMMUSTIX is reliable, it detects all multiple stable fixpoints (SFPs), which is not guaranteed by solving the ODEs, and more efficient than the combinations method. With COMMUSTIX, we studied the dependence of the fixpoint behavior on the competition strengths relative to the intra-specific competition. If inter-specific competition was considerably lower than intra-specific competition, only globally SFPs occurred. In contrast, if all inter-specific was higher than intra-specific competition, multiple SFPs consisting of only one species occurred. If competition strengths in the species pool ranged from below to above the intra-specific competition, either global or multiple SFPs strongly differing in species composition occurred. The species richness over all SFPs was high for pools of species with similar, either weak or strong competition, and lower for species with dissimilar or close to intra-specific competition strengths. The new approach is a reliable and

  7. A Robust Multiple Correlation Coefficient for the Rank Analysis of Linear Models.

    Science.gov (United States)

    1983-09-01

    A multiple correlation coefficient is discussed to measure the degree of association between a random variable Y and a set of random variables X sub...approach of analyzing linear models in a regression, prediction context. The population parameter equals the classical multiple correlation ... coefficient if the multivariate normal model holds but would be more robust for departures from this model. Some results are given on the consistency of the sample estimate and on a test for independence. (Author)

  8. Multiplicity fluctuation and correlation of identified baryons in quark combination model

    CERN Document Server

    Song, Jun; Wang, Rui-qin; Shao, Feng-lan

    2016-01-01

    The dynamical fluctuation and correlation of multiplicity distributions of identified baryons and antibaryons produced by the hadronization of the bulk quark system are systematically studied in quark combination model. Starting from the most basic dynamics of quark combination which are necessary for multiplicity study, we analyze moments (variance, skewness and kurtosis) of inclusive multiplicity distribution of identified baryons, two-baryon multiplicity correlations, and baryon-antibaryon multiplicity correlations after the hadronization of quark system with given quark number and antiquark number. We obtain a series of interesting findings, e.g., binomial behavior of multiplicity moments, coincide flavor dependent two-baryon correlation and universal baryon-antibaryon correlation, which can be regarded as general features of quark combination. We further take into account correlations and fluctuations of quark numbers before hadronization to study their influence on multiple production of baryons and ant...

  9. Maximizing Benefits through Simultaneous Compliance with Multiple Process Models

    Science.gov (United States)

    2011-05-01

    www.abridge-tech.com Example Reference Models CMMI-DEV CMMI-SVC CMMI-ACQ ISO 15504 ISO 9000 AS 9100 ISO 20000 Si Si ITIL x gma Malcolm Baldrige Slide #: 4...and safety Slide #: 6 rbechtold@abridge-tech.comAbridge Technology Abridge Technology www.abridge-tech.com Example Reference Models ITIL

  10. Multiplicity Control in Structural Equation Modeling: Incorporating Parameter Dependencies

    Science.gov (United States)

    Smith, Carrie E.; Cribbie, Robert A.

    2013-01-01

    When structural equation modeling (SEM) analyses are conducted, significance tests for all important model relationships (parameters including factor loadings, covariances, etc.) are typically conducted at a specified nominal Type I error rate ([alpha]). Despite the fact that many significance tests are often conducted in SEM, rarely is…

  11. From Single to Multiple Deficit Models of Developmental Disorders

    Science.gov (United States)

    Pennington, Bruce F.

    2006-01-01

    The emerging etiological model for developmental disorders, like dyslexia, is probabilistic and multifactorial while the prevailing cognitive model has been deterministic and often focused on a single cognitive cause, such as a phonological deficit as the cause of dyslexia. So there is a potential contradiction in our explanatory frameworks for…

  12. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Science.gov (United States)

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  13. Multiple isotope analyses of the pike tapeworm Triaenophorus nodulosus reveal peculiarities in consumer-diet discrimination patterns.

    Science.gov (United States)

    Behrmann-Godel, J; Yohannes, E

    2015-03-01

    Previous studies of dietary isotope discrimination have led to the general expectation that a consumer will exhibit enriched stable isotope levels relative to its diet. Parasite-host systems are specific consumer-diet pairs in which the consumer (parasite) feeds exclusively on one dietary source: host tissue. However, the small numbers of studies previously carried out on isotopic discrimination in parasite-host (ΔXP-HT) systems have yielded controversial results, showing some parasites to be isotopically depleted relative to their food source, while others are enriched or in equilibrium with their hosts. Although the mechanism for these deviations from expectations remains to be understood, possible influences of specific feeding niche or selection for only a few nutritional components by the parasite are discussed. ΔXP-HT for multiple isotopes (δ13C, δ15N, δ34S) were measured in the pike tapeworm Triaenophorus nodulosus and two of its life-cycle fish hosts, perch Perca fluviatilis and pike Esox lucius, within which T. nodulosus occupies different feeding locations. Variability in the value of ΔXP-HT calculated for the parasite and its different hosts indicates an influence of feeding location on isotopic discrimination. In perch liver ΔXP-HT was relatively more negative for all three stable isotopes. In pike gut ΔXP-HT was more positive for δ13C, as expected in conventional consumer-diet systems. For parasites feeding on pike gut, however, the δ15N and δ34S isotope values were comparable with those of the host. We discuss potential causes of these deviations from expectations, including the effect of specific parasite feeding niches, and conclude that ΔXP-HT should be critically evaluated for trophic interactions between parasite and host before general patterns are assumed.

  14. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Directory of Open Access Journals (Sweden)

    Valentina Mengoli

    2014-10-01

    Full Text Available Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on

  15. Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps[C][W][OA

    Science.gov (United States)

    Castruita, Madeli; Casero, David; Karpowicz, Steven J.; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I.; Yan, Weihong; Cokus, Shawn; Loo, Joseph A.; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S.

    2011-01-01

    In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper. PMID:21498682

  16. Microsatellite analysis of Damask rose (Rosa damascena Mill. accessions from various regions in Iran reveals multiple genotypes

    Directory of Open Access Journals (Sweden)

    Naghavi Mohammad

    2007-03-01

    Full Text Available Abstract Background Damask roses (Rosa damascena Mill. are mainly used for essential oil production. Previous studies have indicated that all production material in Bulgaria and Turkey consists of only one genotype. Nine polymorphic microsatellite markers were used to analyze the genetic diversity of 40 accessions of R. damascena collected across major and minor rose oil production areas in Iran. Results All microsatellite markers showed a high level of polymorphism (5–15 alleles per microsatellite marker, with an average of 9.11 alleles per locus. Cluster analysis of genetic similarities revealed that these microsatellites identified a total of nine different genotypes. The genotype from Isfahan province, which is the major production area, was by far the most common genotype (27/40 accessions. It was identical to the Bulgarian genotype. Other genotypes (each represented by 1–4 accessions were collected from minor production areas in several provinces, notably in the mountainous Northwest of Iran. Conclusion This is the first study that uncovered genetic diversity within Damask rose. Our results will guide new collection activities to establish larger collections and manage the Iranian Damask rose genetic resources. The genotypes identified here may be directly useful for breeding.

  17. Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population.

    Science.gov (United States)

    Adelman, Zach N; Kilcullen, Kathleen A; Koganemaru, Reina; Anderson, Michelle A E; Anderson, Troy D; Miller, Dini M

    2011-01-01

    A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD(50) bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.

  18. Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population.

    Directory of Open Access Journals (Sweden)

    Zach N Adelman

    Full Text Available A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I and metabolic resistance to pyrethroid insecticides. Using LD(50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible and Richmond (resistant bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.

  19. Multiple Fan-Beam Optical Tomography: Modelling Techniques

    Directory of Open Access Journals (Sweden)

    Pang Jon Fea

    2009-10-01

    Full Text Available This paper explains in detail the solution to the forward and inverse problem faced in this research. In the forward problem section, the projection geometry and the sensor modelling are discussed. The dimensions, distributions and arrangements of the optical fibre sensors are determined based on the real hardware constructed and these are explained in the projection geometry section. The general idea in sensor modelling is to simulate an artificial environment, but with similar system properties, to predict the actual sensor values for various flow models in the hardware system. The sensitivity maps produced from the solution of the forward problems are important in reconstructing the tomographic image.

  20. Ground Subsidence in the Beijing-Tianjin-Hebei Region from 1992 to 2014 Revealed by Multiple SAR Stacks

    Directory of Open Access Journals (Sweden)

    Yonghong Zhang

    2016-08-01

    Full Text Available The coordinated development of the Beijing-Tianjin-Hebei has become a national strategy with Beijing and Tianjin as twin engines driving the regional development. However, the Beijing-Tianjin-Hebei region has suffered dramatic ground subsidence during last two to three decades, mainly due to long-term groundwater withdrawal. Although, annual spirit leveling has been conducted routinely in some parts of Beijing and Tianjin, and InSAR technique has also been used to monitor ground subsidence in some local areas of the region, there is a lack of a complete survey of ground subsidence over the whole region. In this paper, we report a research on mapping ground subsidence in the Beijing-Tianjin-Hebei region over a long time span from 1992 to 2014. Three SAR datasets from four satellites are used: ERS-1/2 SAR images from 1992 to 2000, ENVISAT ASAR images from 2003 to 2010, and RADARSAT-2 images from 2012 to 2014. An improved multi-temporal InSAR method, namely “Multiple-master Coherent Target Small-Baseline InSAR” (MCTSB-InSAR, has been developed to process the datasets. A unique feature of MCTSB-InSAR is the adjustment process useful for wide area monitoring which provides an integrated solution for both calibration of InSAR-derived deformation and the harmonization of the deformation estimates from overlapping SAR frames. Three maps of the subsidence rate corresponding to the three periods over the wide Beijing-Tianjin-Hebei region are generated, with respective accuracy of 8.7 mm/year (1992–2000, 4.7 mm/year (2003–2010, and 5.4 mm/year (2012–2014 validated by more than 120 leveling measurements. The spatial-temporal characteristics of the development of ground subsidence in Beijing and Tianjin are analyzed. This research represents a first-ever effort on mapping ground subsidence over very large area and over long time span in China. The result is of significance to serve the decision-making on ground subsidence mitigation in the Beijing

  1. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder.

    Science.gov (United States)

    Sarachana, Tewarit; Hu, Valerie W

    2013-05-22

    We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as

  2. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  3. Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Magdalene Nakou

    Full Text Available BACKGROUND: Gene profiling studies provide important information for key molecules relevant to a disease but are less informative of protein-protein interactions, post-translational modifications and regulation by targeted subcellular localization. Integration of genomic data and construction of functional gene networks may provide additional insights into complex diseases such as systemic lupus erythematosus (SLE. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed gene expression microarray data of bone marrow mononuclear cells (BMMCs from 20 SLE patients (11 with active disease and 10 controls. Gene networks were constructed using the bioinformatic tool Ingenuity Gene Network Analysis. In SLE patients, comparative analysis of BMMCs genes revealed a network with 19 central nodes as major gene regulators including ERK, JNK, and p38 MAP kinases, insulin, Ca(2+ and STAT3. Comparison between active versus inactive SLE identified 30 central nodes associated with immune response, protein synthesis, and post-transcriptional modification. A high degree of identity between networks in active SLE and non-Hodgkin's lymphoma (NHL patients was found, with overlapping central nodes including kinases (MAPK, ERK, JNK, PKC, transcription factors (NF-kappaB, STAT3, and insulin. In validation studies, western blot analysis in splenic B cells from 5-month-old NZB/NZW F1 lupus mice showed activation of STAT3, ITGB2, HSPB1, ERK, JNK, p38, and p32 kinases, and downregulation of FOXO3 and VDR compared to normal C57Bl/6 mice. CONCLUSIONS/SIGNIFICANCE: Gene network analysis of lupus BMMCs identified central gene regulators implicated in disease pathogenesis which could represent targets of novel therapies in human SLE. The high similarity between active SLE and NHL networks provides a molecular basis for the reported association of the former with lymphoid malignancies.

  4. Multilocus assignment analyses reveal multiple units and rare migration events in the recently expanded yellow-eyed penguin (Megadyptes antipodes).

    Science.gov (United States)

    Boessenkool, Sanne; Star, Bastiaan; Waters, Jonathan M; Seddon, Philip J

    2009-06-01

    The identification of demographically independent populations and the recognition of management units have been greatly facilitated by the continuing advances in genetic tools. Managements units now play a key role in short-term conservation management programmes of declining species, but their importance in expanding populations receives comparatively little attention. The endangered yellow-eyed penguin (Megadyptes antipodes) expanded its range from the subantarctic to New Zealand's South Island a few hundred years ago and this new population now represents almost half of the species' total census size. This dramatic expansion attests to M. antipodes' high dispersal abilities and suggests the species is likely to constitute a single demographic population. Here we test this hypothesis of panmixia by investigating genetic differentiation and levels of gene flow among penguin breeding areas using 12 autosomal microsatellite loci along with mitochondrial control region sequence analyses for 350 individuals. Contrary to our hypothesis, however, the analyses reveal two genetically and geographically distinct assemblages: South Island vs. subantarctic populations. Using assignment tests, we recognize just two first-generation migrants between these populations (corresponding to a migration rate of < 2%), indicating that ongoing levels of long-distance migration are low. Furthermore, the South Island population has low genetic variability compared to the subantarctic population. These results suggest that the South Island population was founded by only a small number of individuals, and that subsequent levels of gene flow have remained low. The demographic independence of the two populations warrants their designation as distinct management units and conservation efforts should be adjusted accordingly to protect both populations.

  5. Multiple loss-of-function 5-O-glucosyltransferase alleles revealed in Vitis vinifera, but not in other Vitis species.

    Science.gov (United States)

    Yang, Yingzhen; Labate, Joanne A; Liang, Zhenchang; Cousins, Peter; Prins, Bernard; Preece, John E; Aradhya, Mallikarjuna; Zhong, Gan-Yuan

    2014-11-01

    Wild and loss-of-function alleles of the 5 - O - glucosyltransferase gene responsible for synthesis of diglucoside anthocyanins in Vitis were characterized. The information aids marker development for tracking this gene in grape breeding. Anthocyanins in red grapes are present in two glycosylation states: monoglucoside (3-O-glucoside) and diglucoside (3, 5-di-O-glucoside). While monoglucoside anthocyanins are present in all pigmented grapes, diglucoside anthocyanins are rarely found in the cultivated grape species Vitis vinifera. Biochemically 3-O-glucoside anthocyanins can be converted into 3,5-di-O-glucoside anthocyanins by a 5-O-glucosyltransferase. In this study, we surveyed allelic variation of the 5-O-glucosyltransferase gene (5GT) in 70 V. vinifera ssp. vinifera cultivars, 52 V. vinifera ssp. sylvestris accessions, 23 Vitis hybrid grapes, and 22 accessions of seven other Vitis species. Eighteen 5GT alleles with apparent loss-of-function mutations, including seven premature stop codon mutations and six frameshift indel mutations, were discovered in V. vinifera, but not in the other Vitis species. A total of 36 5GT alleles without apparent loss-of-function mutations (W-type) were identified. These W-type alleles were predominantly present in wild Vitis species, although a few of them were also found in some V. vinifera accessions. We further evaluated some of these 5GT alleles in producing diglucoside anthocyanins by analyzing the content of diglucoside anthocyanins in a set of representative V. vinifera cultivars. Through haplotype network analysis we revealed that V. vinifera ssp. vinifera and its wild progenitor V. vinifera ssp. sylvestris shared many loss-of-function 5GT alleles and extensive divergence of the 5GT alleles was evident within V. vinifera. This work advances our understanding of the genetic diversity of 5GT and provides a molecular basis for future marker-assisted selection for improving this important wine quality trait.

  6. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Science.gov (United States)

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  7. Modeling of 3D Woven Composites Containing Multiple Delaminations

    Science.gov (United States)

    2012-08-20

    researchers 3D woven composites shows better damage tolerance than laminated textile composites without z-yarns such as plain woven composites even...modeling of quasi-static short beam shear test of plain woven laminated composites. Cohesive elements were used in regions where transverse cracks and...Title ABSTRACT In this paper we present FE modeling of quasi-static short beam shear test of plain woven laminated composites. Cohesive elements were

  8. Reducing Lag in Virtual Displays Using Multiple Model Adaptive Estimation

    Science.gov (United States)

    1995-12-01

    time varying behavior. Kleinman [4] proposed an optimal control model for human performance in a closed loop. This model interprets human perception as a...Washington, D. C: NASA, 1963. 3. Arthur , Kevin W., Kellogg, S. Booth, Colin Ware, Evaluating 3D Task Performance for Fish Tank Virtual Worlds," ACM...of Describing Behavior," Human Factors, volume 19, number 4,1977. 13. Kozak, J. J., P. A. Hancock, E. J. Arthur , S. T. Chrysler, "Transfer of Training

  9. Mathematical and computational modeling in biology at multiple scales

    OpenAIRE

    Tuszynski, Jack A; Winter, Philip; White, Diana; Tseng, Chih-Yuan; Sahu, Kamlesh K.; Gentile, Francesco; Spasevska, Ivana; Omar, Sara Ibrahim; Nayebi, Niloofar; Churchill, Cassandra DM; Klobukowski, Mariusz; El-Magd, Rabab M Abou

    2014-01-01

    A variety of topics are reviewed in the area of mathematical and computational modeling in biology, covering the range of scales from populations of organisms to electrons in atoms. The use of maximum entropy as an inference tool in the fields of biology and drug discovery is discussed. Mathematical and computational methods and models in the areas of epidemiology, cell physiology and cancer are surveyed. The technique of molecular dynamics is covered, with special attention to force fields f...

  10. Applying a Multiple Group Causal Indicator Modeling Framework to the Reading Comprehension Skills of Third, Seventh, and Tenth Grade Students

    Science.gov (United States)

    Tighe, Elizabeth L.; Wagner, Richard K.; Schatschneider, Christopher

    2015-01-01

    This study demonstrates the utility of applying a causal indicator modeling framework to investigate important predictors of reading comprehension in third, seventh, and tenth grade students. The results indicated that a 4-factor multiple indicator multiple indicator cause (MIMIC) model of reading comprehension provided adequate fit at each grade level. This model included latent predictor constructs of decoding, verbal reasoning, nonverbal reasoning, and working memory and accounted for a large portion of the reading comprehension variance (73% to 87%) across grade levels. Verbal reasoning contributed the most unique variance to reading comprehension at all grade levels. In addition, we fit a multiple group 4-factor MIMIC model to investigate the relative stability (or variability) of the predictor contributions to reading comprehension across development (i.e., grade levels). The results revealed that the contributions of verbal reasoning, nonverbal reasoning, and working memory to reading comprehension were stable across the three grade levels. Decoding was the only predictor that could not be constrained to be equal across grade levels. The contribution of decoding skills to reading comprehension was higher in third grade and then remained relatively stable between seventh and tenth grade. These findings illustrate the feasibility of using MIMIC models to explain individual differences in reading comprehension across the development of reading skills. PMID:25821346

  11. Simple multiple regression model for long range forecasting of Indian summer monsoon rainfall

    Digital Repository Service at National Institute of Oceanography (India)

    Sadhuram, Y.; Murthy, T.V.R.

    ) and ISMR is found to be 0.62. The multiple correlation using the above two parameters is 0.85 which explains 72% variance in ISMR. Using the above two parameters a linear multiple regression model to predict ISMR is developed. The results are comparable...

  12. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

    Directory of Open Access Journals (Sweden)

    Croft Larry

    2012-07-01

    Full Text Available Abstract Background Transcription factors (TFs have long been known to be principally activators of transcription in eukaryotes and prokaryotes. The growing awareness of the ubiquity of microRNAs (miRNAs as suppressive regulators in eukaryotes, suggests the possibility of a mutual, preferential, self-regulatory connectivity between miRNAs and TFs. Here we investigate the connectivity from TFs and miRNAs to other genes and each other using text mining, TF promoter binding site and 6 different miRNA binding site prediction methods. Results In the first approach text mining of PubMed abstracts reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3’UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes. Furthermore, a random sample of 986 TarBase entries was scored for experimental evidence by manual inspection of the original papers, and enrichment for TFs was observed to increase with score. Low-scoring TarBase entries, where experimental evidence is anticorrelated miRNA:mRNA expression with predicted miRNA targets, appear not to select for real miRNA targets to any degree. Our manually validated text-mining results also suggests that miRNAs may be activated by more TFs than other classes of genes, as 7% of miRNA:TF co-occurrences in the literature were TFs activating miRNAs. This was confirmed when thirdly, we found enrichment for predicted, conserved TF binding sites in miRNA and TF genes compared to other gene classes. Conclusions We see enrichment of connections between miRNAs and TFs using several independent methods, suggestive of a network of mutual activating and suppressive regulation. We have also built regulatory networks (containing 2- and 3-loop motifs for mouse and human using predicted miRNA and TF binding sites and we have developed a web server

  13. Quantitative proteome analysis of an antibiotic resistant Escherichia coli exposed to tetracycline reveals multiple affected metabolic and peptidoglycan processes.

    Science.gov (United States)

    Jones-Dias, Daniela; Carvalho, Ana Sofia; Moura, Inês Barata; Manageiro, Vera; Igrejas, Gilberto; Caniça, Manuela; Matthiesen, Rune

    2017-03-06

    Tetracyclines are among the most commonly used antibiotics administrated to farm animals for disease treatment and prevention, contributing to the worldwide increase in antibiotic resistance in animal and human pathogens. Although tetracycline mechanisms of resistance are well known, the role of metabolism in bacterial reaction to antibiotic stress is still an important assignment and could contribute to the understanding of tetracycline related stress response. In this study, spectral counts-based label free quantitative proteomics has been applied to study the response to tetracycline of the environmental-borne Escherichia coli EcAmb278 isolate soluble proteome. A total of 1484 proteins were identified by high resolution mass spectrometry at a false discovery rate threshold of 1%, of which 108 were uniquely identified under absence of tetracycline whereas 126 were uniquely identified in presence of tetracycline. These proteins revealed interesting difference in e.g. proteins involved in peptidoglycan-based cell wall proteins and energy metabolism. Upon treatment, 12 proteins were differentially regulated showing more than 2-fold change and presistant E. coli provides novel insight into tetracycline related stress. The lack of new antibiotics to fight infections caused by multidrug resistant microorganisms has motivated the use of old antibiotics, and the search for new drug targets. The evolution of antibiotic resistance is complex, but it is known that agroecosystems play an important part in the selection of antibiotic resistance bacteria. Tetracyclines are still used as phytopharmaceutical agents in crops, selecting resistant bacteria and changing the ecology of farm soil. Little is known about the metabolic response of genetically resistant populations to antibiotic exposure. Indeed, to date there are no quantitative tetracycline resistance studies performed with the latest generation of high resolution mass spectrometers allowing high mass accuracy in both

  14. Complex adaptive responses during antagonistic coevolution between Tribolium castaneum and its natural parasite Nosema whitei revealed by multiple fitness components

    Directory of Open Access Journals (Sweden)

    Bérénos Camillo

    2012-01-01

    Full Text Available Abstract Background Host-parasite coevolution can lead to local adaptation of either parasite or host if there is specificity (GxG interactions and asymmetric evolutionary potential between host and parasite. This has been demonstrated both experimentally and in field studies, but a substantial proportion of studies fail to detect such clear-cut patterns. One explanation for this is that adaptation can be masked by counter-adaptation by the antagonist. Additionally, genetic architecture underlying the interaction is often highly complex thus preventing specific adaptive responses. Here, we have employed a reciprocal cross-infection experiment to unravel the adaptive responses of two components of fitness affecting both parties with different complexities of the underlying genetic architecture (i.e. mortality and spore load. Furthermore, our experimental coevolution of hosts (Tribolium castaneum and parasites (Nosema whitei included paired replicates of naive hosts from identical genetic backgrounds to allow separation between host- and parasite-specific responses. Results In hosts, coevolution led to higher resistance and altered resistance profiles compared to paired control lines. Host genotype × parasite genotype interactions (GH × GP were observed for spore load (the trait of lower genetic complexity, but not for mortality. Overall parasite performance correlated with resistance of its matching host coevolution background reflecting a directional and unspecific response to strength of selection during coevolution. Despite high selective pressures exerted by the obligatory killing parasite, and host- and parasite-specific mortality profiles, no general pattern of local adaptation was observed, but one case of parasite maladaptation was consistently observed on both coevolved and control host populations. In addition, the use of replicate control host populations in the assay revealed one case of host maladaptation and one case of parasite

  15. A measurement model of multiple intelligence profiles of management graduates

    Science.gov (United States)

    Krishnan, Heamalatha; Awang, Siti Rahmah

    2017-05-01

    In this study, developing a fit measurement model and identifying the best fitting items to represent Howard Gardner's nine intelligences namely, musical intelligence, bodily-kinaesthetic intelligence, mathematical/logical intelligence, visual/spatial intelligence, verbal/linguistic intelligence, interpersonal intelligence, intrapersonal intelligence, naturalist intelligence and spiritual intelligence are the main interest in order to enhance the opportunities of the management graduates for employability. In order to develop a fit measurement model, Structural Equation Modeling (SEM) was applied. A psychometric test which is the Ability Test in Employment (ATIEm) was used as the instrument to measure the existence of nine types of intelligence of 137 University Teknikal Malaysia Melaka (UTeM) management graduates for job placement purposes. The initial measurement model contains nine unobserved variables and each unobserved variable is measured by ten observed variables. Finally, the modified measurement model deemed to improve the Normed chi-square (NC) = 1.331; Incremental Fit Index (IFI) = 0.940 and Root Mean Square of Approximation (RMSEA) = 0.049 was developed. The findings showed that the UTeM management graduates possessed all nine intelligences either high or low. Musical intelligence, mathematical/logical intelligence, naturalist intelligence and spiritual intelligence contributed highest loadings on certain items. However, most of the intelligences such as bodily kinaesthetic intelligence, visual/spatial intelligence, verbal/linguistic intelligence interpersonal intelligence and intrapersonal intelligence possessed by UTeM management graduates are just at the borderline.

  16. Simple model for multiple-choice collective decision making.

    Science.gov (United States)

    Lee, Ching Hua; Lucas, Andrew

    2014-11-01

    We describe a simple model of heterogeneous, interacting agents making decisions between n≥2 discrete choices. For a special class of interactions, our model is the mean field description of random field Potts-like models and is effectively solved by finding the extrema of the average energy E per agent. In these cases, by studying the propagation of decision changes via avalanches, we argue that macroscopic dynamics is well captured by a gradient flow along E. We focus on the permutation symmetric case, where all n choices are (on average) the same, and spontaneous symmetry breaking (SSB) arises purely from cooperative social interactions. As examples, we show that bimodal heterogeneity naturally provides a mechanism for the spontaneous formation of hierarchies between decisions and that SSB is a preferred instability to discontinuous phase transitions between two symmetric points. Beyond the mean field limit, exponentially many stable equilibria emerge when we place this model on a graph of finite mean degree. We conclude with speculation on decision making with persistent collective oscillations. Throughout the paper, we emphasize analogies between methods of solution to our model and common intuition from diverse areas of physics, including statistical physics and electromagnetism.

  17. Procedural Modeling for Rapid-Prototyping of Multiple Building Phases

    Science.gov (United States)

    Saldana, M.; Johanson, C.

    2013-02-01

    RomeLab is a multidisciplinary working group at UCLA that uses the city of Rome as a laboratory for the exploration of research approaches and dissemination practices centered on the intersection of space and time in antiquity. In this paper we present a multiplatform workflow for the rapid-prototyping of historical cityscapes through the use of geographic information systems, procedural modeling, and interactive game development. Our workflow begins by aggregating archaeological data in a GIS database. Next, 3D building models are generated from the ArcMap shapefiles in Esri CityEngine using procedural modeling techniques. A GIS-based terrain model is also adjusted in CityEngine to fit the building elevations. Finally, the terrain and city models are combined in Unity, a game engine which we used to produce web-based interactive environments which are linked to the GIS data using keyhole markup language (KML). The goal of our workflow is to demonstrate that knowledge generated within a first-person virtual world experience can inform the evaluation of data derived from textual and archaeological sources, and vice versa.

  18. Coupled biophysical global ocean model and molecular genetic analyses identify multiple introductions of cryptogenic species.

    Science.gov (United States)

    Dawson, Michael N; Sen Gupta, Alex; England, Matthew H

    2005-08-23

    The anthropogenic introduction of exotic species is one of the greatest modern threats to marine biodiversity. Yet exotic species introductions remain difficult to predict and are easily misunderstood because knowledge of natural dispersal patterns, species diversity, and biogeography is often insufficient to distinguish between a broadly dispersed natural population and an exotic one. Here we compare a global molecular phylogeny of a representative marine meroplanktonic taxon, the moon-jellyfish Aurelia, with natural dispersion patterns predicted by a global biophysical ocean model. Despite assumed high dispersal ability, the phylogeny reveals many cryptic species and predominantly regional structure with one notable exception: the globally distributed Aurelia sp.1, which, molecular data suggest, may occasionally traverse the Pacific unaided. This possibility is refuted by the ocean model, which shows much more limited dispersion and patterns of distribution broadly consistent with modern biogeographic zones, thus identifying multiple introductions worldwide of this cryptogenic species. This approach also supports existing evidence that (i) the occurrence in Hawaii of Aurelia sp. 4 and other native Indo-West Pacific species with similar life histories is most likely due to anthropogenic translocation, and (ii) there may be a route for rare natural colonization of northeast North America by the European marine snail Littorina littorea, whose status as endemic or exotic is unclear.

  19. The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Badea, Alexandra; Kane, Lauren; Anderson, Robert J; Qi, Yi; Foster, Mark; Cofer, Gary P; Medvitz, Neil; Buckley, Anne F; Badea, Andreas K; Wetsel, William C; Colton, Carol A

    2016-11-15

    Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination-through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy.

  20. Segmenting multiple overlapping objects via a hybrid active contour model incorporating shape priors: applications to digital pathology

    Science.gov (United States)

    Ali, Sahirzeeshan; Madabhushi, Anant

    2011-03-01

    Active contours and active shape models (ASM) have been widely employed in image segmentation. A major limitation of active contours, however, is in their (a) inability to resolve boundaries of intersecting objects and to (b) handle occlusion. Multiple overlapping objects are typically segmented out as a single object. On the other hand, ASMs are limited by point correspondence issues since object landmarks need to be identified across multiple objects for initial object alignment. ASMs are also are constrained in that they can usually only segment a single object in an image. In this paper, we present a novel synergistic boundary and region-based active contour model that incorporates shape priors in a level set formulation. We demonstrate an application of these synergistic active contour models using multiple level sets to segment nuclear and glandular structures on digitized histopathology images of breast and prostate biopsy specimens. Unlike previous related approaches, our model is able to resolve object overlap and separate occluded boundaries of multiple objects simultaneously. The energy functional of the active contour is comprised of three terms. The first term comprises the prior shape term, modeled on the object of interest, thereby constraining the deformation achievable by the active contour. The second term, a boundary based term detects object boundaries from image gradients. The third term drives the shape prior and the contour towards the object boundary based on region statistics. The results of qualitative and quantitative evaluation on 100 prostate and 14 breast cancer histology images for the task of detecting and segmenting nuclei, lymphocytes, and glands reveals that the model easily outperforms two state of the art segmentation schemes (Geodesic Active Contour (GAC) and Roussons shape based model) and resolves up to 92% of overlapping/occluded lymphocytes and nuclei on prostate and breast cancer histology images.

  1. Modeling of plates with multiple anisotropic layers and residual stress

    DEFF Research Database (Denmark)

    Engholm, Mathias; Pedersen, Thomas; Thomsen, Erik Vilain

    2016-01-01

    Usually the analytical approach for modeling of plates uses the single layer plate equation to obtain the deflection and does not take anisotropy and residual stress into account. Based on the stress–strain relation of each layer and balancing stress resultants and bending moments, a general...... multilayered anisotropic plate equation is developed for plates with an arbitrary number of layers. The exact deflection profile is calculated for a circular clamped plate of anisotropic materials with residual bi-axial stress.From the deflection shape the critical stress for buckling is calculated......, and an excellent agreement between the two models is seen with a relative difference of less than 2% for all calculations. The model was also used to extract the cell capacitance, the parasitic capacitance and the residual stress of a pressure sensor composed of a multilayered plate of silicon and silicon oxide...

  2. Dynamic information architecture system (DIAS) : multiple model simulation management.

    Energy Technology Data Exchange (ETDEWEB)

    Simunich, K. L.; Sydelko, P.; Dolph, J.; Christiansen, J.

    2002-05-13

    Dynamic Information Architecture System (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex multidisciplinary simulations of a wide variety of application contexts. The modeling domain of a specific DIAS-based simulation is determined by (1) software Entity (domain-specific) objects that represent the real-world entities that comprise the problem space (atmosphere, watershed, human), and (2) simulation models and other data processing applications that express the dynamic behaviors of the domain entities. In DIAS, models communicate only with Entity objects, never with each other. Each Entity object has a number of Parameter and Aspect (of behavior) objects associated with it. The Parameter objects contain the state properties of the Entity object. The Aspect objects represent the behaviors of the Entity object and how it interacts with other objects. DIAS extends the ''Object'' paradigm by abstraction of the object's dynamic behaviors, separating the ''WHAT'' from the ''HOW.'' DIAS object class definitions contain an abstract description of the various aspects of the object's behavior (the WHAT), but no implementation details (the HOW). Separate DIAS models/applications carry the implementation of object behaviors (the HOW). Any model deemed appropriate, including existing legacy-type models written in other languages, can drive entity object behavior. The DIAS design promotes plug-and-play of alternative models, with minimal recoding of existing applications. The DIAS Context Builder object builds a constructs or scenario for the simulation, based on developer specification and user inputs. Because DIAS is a discrete event simulation system, there is a Simulation Manager object with which all events are processed. Any class that registers to receive events must implement an event handler (method) to process the event during execution. Event handlers

  3. Modeling Customer Lifetimes with Multiple Causes of Churn

    OpenAIRE

    Michael Braun; David A. Schweidel

    2011-01-01

    Customer retention and customer churn are key metrics of interest to marketers, but little attention has been placed on linking the different reasons for which customers churn to their value to a contractual service provider. In this paper, we put forth a hierarchical competing-risk model to jointly model when customers choose to terminate their service and why. Some of these reasons for churn can be influenced by the firm (e.g., service problems or price–value trade-offs), but others are unc...

  4. Iron deposition is independent of cellular inflammation in a cerebral model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lee Phil

    2011-06-01

    Full Text Available Abstract Background Perivenular inflammation is a common early pathological feature in multiple sclerosis (MS. A recent hypothesis stated that CNS inflammation is induced by perivenular iron deposits that occur in response to altered blood flow in MS subjects. In order to evaluate this hypothesis, an animal model was developed, called cerebral experimental autoimmune encephalomyelitis (cEAE, which presents with CNS perivascular iron deposits. This model was used to investigate the relationship of iron deposition to inflammation. Methods In order to generate cEAE, mice were given an encephalitogen injection followed by a stereotactic intracerebral injection of TNF-α and IFN-γ. Control animals received encephalitogen followed by an intracerebral injection of saline, or no encephalitogen plus an intracerebral injection of saline or cytokines. Laser Doppler was used to measure cerebral blood flow. MRI and iron histochemistry were used to localize iron deposits. Additional histological procedures were used to localize inflammatory cell infiltrates, microgliosis and astrogliosis. Results Doppler analysis revealed that cEAE mice had a reduction in cerebral blood flow compared to controls. MRI revealed T2 hypointense areas in cEAE animals that spatially correlated with iron deposition around vessels and at some sites of inflammation as detected by iron histochemistry. Vessels with associated iron deposits were distributed across both hemispheres. Mice with cEAE had more iron-labeled vessels compared to controls, but these vessels were not commonly associated with inflammatory cell infiltrates. Some iron-laden vessels had associated microgliosis that was above the background microglial response, and iron deposits were observed within reactive microglia. Vessels with associated astrogliosis were more commonly observed without colocalization of iron deposits. Conclusion The findings indicate that iron deposition around vessels can occur independently of

  5. Long-run growth rate in a random multiplicative model

    Energy Technology Data Exchange (ETDEWEB)

    Pirjol, Dan [Institute for Physics and Nuclear Engineering, 077125 Bucharest (Romania)

    2014-08-01

    We consider the long-run growth rate of the average value of a random multiplicative process x{sub i+1} = a{sub i}x{sub i} where the multipliers a{sub i}=1+ρexp(σW{sub i}₋1/2 σ²t{sub i}) have Markovian dependence given by the exponential of a standard Brownian motion W{sub i}. The average value (x{sub n}) is given by the grand partition function of a one-dimensional lattice gas with two-body linear attractive interactions placed in a uniform field. We study the Lyapunov exponent λ=lim{sub n→∞}1/n log(x{sub n}), at fixed β=1/2 σ²t{sub n}n, and show that it is given by the equation of state of the lattice gas in thermodynamical equilibrium. The Lyapunov exponent has discontinuous partial derivatives along a curve in the (ρ, β) plane ending at a critical point (ρ{sub C}, β{sub C}) which is related to a phase transition in the equivalent lattice gas. Using the equivalence of the lattice gas with a bosonic system, we obtain the exact solution for the equation of state in the thermodynamical limit n → ∞.

  6. Intelligent control using multiple models based on on-line learning

    Institute of Scientific and Technical Information of China (English)

    Junyong ZHAI; Shumin FEI; Feipeng DA

    2006-01-01

    In this paper we deal with the problem of plants with large parameter variations under different operating modes. A novel intelligent control algorithm based on multiple models is proposed to improve the dynamical response performance. At the same time adaptive model bank is applied to establish models without prior system information.Multiple models and corresponding controllers are automatically established on-line by a conventionally adaptive model and a re-initialized one. A best controller is chosen by the performance function at every instant. The closed-loop system's stability and asymptotical convergence of tracking error can be guaranteed. Simulation results have confirmed the validity of the proposed method.

  7. On the thermoluminescent interactive multiple-trap system (IMTS) model: is it a simple model?

    Energy Technology Data Exchange (ETDEWEB)

    Gil T, M. I.; Perez C, L. [UNAM, Facultad de Quimica, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico); Cruz Z, E.; Furetta, C.; Roman L, J., E-mail: ecruz@nucleares.unam.mx [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico)

    2016-10-15

    In the thermally stimulated luminescence phenomenon, named thermoluminescence (Tl), the electrons and holes generated by the radiation-matter interaction can be trapped by the metastable levels in the band gap of the solid. Following, the electron can be thermally releases into the conduction band and a radiatively recombination with hole close to the recombination center occurred and the glow curve is emitted. However, the complex mechanism of trapping and thermally releases occurred in the band gap of solid. Some models, such as; first, second and general-order kinetics, have been well established to explain the behaviour of the glow curves and their defects recombination mechanism. In this work, expressions for and Interactive Multiple-Trap System model (IMTS) was obtained assuming: a set of discrete electron traps (active traps At), another set of thermally disconnected trap (TDT) and a recombination center (Rc) too. A numerical analysis based on the Levenberg-Marquardt method in conjunction with an implicit Rosenbrock method was taken into account to simulate the glow curve. The numerical method was tested through synthetic Tl glow curves for a wide range of trap parameters. The activation energy and kinetics order were determined using values from the General Order Kinetics (GOK) model as entry data to IMTS model. This model was tested using the experimental glow curves obtained from Ce or Eu-doped MgF{sub 2}(LiF) polycrystals samples. Results shown that the IMTS model can predict more accurately the behavior of the Tl glow curves that those obtained by the GOK modified by Rasheedy and by the Mixed Order Kinetics model. (Author)

  8. A preference-based multiple-source rough set model

    NARCIS (Netherlands)

    M.A. Khan; M. Banerjee

    2010-01-01

    We propose a generalization of Pawlak’s rough set model for the multi-agent situation, where information from an agent can be preferred over that of another agent of the system while deciding membership of objects. Notions of lower/upper approximations are given which depend on the knowledge base of

  9. Dynamic model for power systems with multiple FACTS controllers

    Energy Technology Data Exchange (ETDEWEB)

    Radman, Ghadir; Raje, Reshma S. [Center for Energy Systems Research, Tennessee Technological University, P.O. Box 5004, Cookeville, TN 38505 (United States)

    2008-03-15

    Computer simulation and analysis of power systems are necessary for both planning and operation. This requires an appropriate mathematical model of the system that includes many inter-related linear/nonlinear differential and algebraic equations. Such mathematical model is also needed for the design of globally coordinated controllers to improve power system dynamic performance and stability. This paper presents a procedure for finding comprehensive dynamic models of power systems fitted with shunt and/or series connected FACTS controllers such as STATCOM, SSSC, and UPFC. In this procedure, individual components of a power system are modeled using appropriate frame of references. Then all related equations are transformed to a common network frame of reference and tied to each other through the Y-matrix of the transmission network. The procedure is tested on the Western System Coordinating Council (WSCC) test system including FACTS controllers by performing computer simulations of the system for three-phase short circuit faults. MATLAB/Simulink software package is used for the simulations. (author)

  10. A semianalytic model for the productivity testing of multiple wells

    NARCIS (Netherlands)

    Fokker, P.A.; Verga, F.

    2008-01-01

    We present a semianalytic method for modeling the productivity testing of vertical, horizontal, slanted, or multilateral wells. The method is applicable to both oil and gas reservoirs and automatically accounts for well interference. The use of analytic expressions ensures that short-time transient

  11. Stochastic modeling of Lake Van water level time series with jumps and multiple trends

    Directory of Open Access Journals (Sweden)

    H. Aksoy

    2013-06-01

    Full Text Available In the 1990s, water level in the closed-basin Lake Van located in the Eastern Anatolia, Turkey, has risen up about 2 m. Analysis of the hydrometeorological data shows that change in the water level is related to the water budget of the lake. In this study, stochastic models are proposed for simulating monthly water level data. Two models considering mono- and multiple-trend time series are developed. The models are derived after removal of trend and periodicity in the dataset. Trend observed in the lake water level time series is fitted by mono- and multiple-trend lines. In the so-called mono-trend model, the time series is treated as a whole under the hypothesis that the lake water level has an increasing trend. In the second model (so-called multiple-trend, the time series is divided into a number of segments to each a linear trend can be fitted separately. Application on the lake water level data shows that four segments, each fitted with a trend line, are meaningful. Both the mono- and multiple-trend models are used for simulation of synthetic lake water level time series under the hypothesis that the observed mono- and multiple-trend structure of the lake water level persist during the simulation period. The multiple-trend model is found better for planning the future infrastructural projects in surrounding areas of the lake as it generates higher maxima for the simulated lake water level.

  12. Discriminative accuracy of genomic profiling comparing multiplicative and additive risk models.

    Science.gov (United States)

    Moonesinghe, Ramal; Khoury, Muin J; Liu, Tiebin; Janssens, A Cecile J W

    2011-02-01

    Genetic prediction of common diseases is based on testing multiple genetic variants with weak effect sizes. Standard logistic regression and Cox Proportional Hazard models that assess the combined effect of multiple variants on disease risk assume multiplicative joint effects of the variants, but this assumption may not be correct. The risk model chosen may affect the predictive accuracy of genomic profiling. We investigated the discriminative accuracy of genomic profiling by comparing additive and multiplicative risk models. We examined genomic profiles of 40 variants with genotype frequencies varying from 0.1 to 0.4 and relative risks varying from 1.1 to 1.5 in separate scenarios assuming a disease risk of 10%. The discriminative accuracy was evaluated by the area under the receiver operating characteristic curve. Predicted risks were more extreme at the lower and higher risks for the multiplicative risk model compared with the additive model. The discriminative accuracy was consistently higher for multiplicative risk models than for additive risk models. The differences in discriminative accuracy were negligible when the effect sizes were small (risk genotypes were common or when they had stronger effects. Unraveling the exact mode of biological interaction is important when effect sizes of genetic variants are moderate at the least, to prevent the incorrect estimation of risks.

  13. Divergence with gene flow between Ponto-Caspian refugia in an anadromous cyprinid Rutilus frisii revealed by multiple gene phylogeography.

    Science.gov (United States)

    Kotlík, Petr; Marková, Silvia; Choleva, Lukás; Bogutskaya, Nina G; Ekmekçi, F Guler; Ivanova, Petya P

    2008-02-01

    The Black and Caspian Seas have experienced alternating periods of isolation and interconnection over many Milankovitch climate oscillations and most recently became separated when the meltwater overflow from the Caspian Sea ceased at the end of the last glaciation. Climate-induced habitat changes have indisputably had profound impacts on distribution and demography of aquatic species, yet uncertainties remain about the relative roles of isolation and dispersal in the response of species shared between the Black and Caspian Sea basins. We examined these issues using phylogeographical analysis of an anadromous cyprinid fish Rutilus frisii. Bayesian coalescence analyses of sequence variation at two nuclear and one mitochondrial genes suggest that the Black and Caspian Seas supported separate populations of R. frisii during the last glaciation. Parameter estimates from the fitted isolation-with-migration model showed that their separation was not complete, however, and that the two populations continued to exchange genes in both directions. These analyses also suggested that majority of migrations occurred during the Pleistocene, showing that the variation shared between the Black and Caspian Seas is the result of ancient dispersal along the temporary natural connections between the basins, rather than of incomplete lineage sorting or recent human-mediated dispersal. Gene flow between the refugial populations was therefore an important source of genetic variation, and we suggest that it facilitated the evolutionary response of the populations to changing climate.

  14. Stochastic modeling of Lake Van water level time series with jumps and multiple trends

    Directory of Open Access Journals (Sweden)

    H. Aksoy

    2013-02-01

    Full Text Available In 1990s, water level in the closed-basin Lake Van located in the Eastern Anatolia, Turkey has risen up about 2 m. Analysis of the hydrometeorological shows that change in the water level is related to the water budget of the lake. In this study, a stochastic model is generated using the measured monthly water level data of the lake. The model is derived after removal of trend and periodicity in the data set. Trend observed in the lake water level time series is fitted by mono- and multiple-trend lines. For the multiple-trend, the time series is first divided into homogeneous segments by means of SEGMENTER, segmentation software. Four segments are found meaningful practically each fitted with a trend line. Two models considering mono- and multiple-trend time series are developed. The multiple-trend model is found better for planning future development in surrounding areas of the lake.

  15. Visualizing a Dusty Plasma Shock Wave via Interacting Multiple-Model Mode Probabilities

    OpenAIRE

    Oxtoby, Neil P.; Ralph, Jason F.; Durniak, Céline; Samsonov, Dmitry

    2011-01-01

    Particles in a dusty plasma crystal disturbed by a shock wave are tracked using a three-mode interacting multiple model approach. Color-coded mode probabilities are used to visualize the shock wave propagation through the crystal.

  16. Multiple integral representation for the trigonometric SOS model with domain wall boundaries

    CERN Document Server

    Galleas, W

    2011-01-01

    Using the dynamical Yang-Baxter algebra we derive a functional equation for the partition function of the trigonometric SOS model with domain wall boundary conditions. The solution of the equation is given in terms of a multiple contour integral.

  17. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models

    National Research Council Canada - National Science Library

    Preacher, Kristopher J; Hayes, Andrew F

    2008-01-01

    .... We provide an overview of simple and multiple mediation and explore three approaches that can be used to investigate indirect processes, as well as methods for contrasting two or more mediators within a single model...

  18. A geospatial modelling approach to predict seagrass habitat recovery under multiple stressor regimes

    Science.gov (United States)

    Restoration of estuarine seagrass habitats requires a clear understanding of the modes of action of multiple interacting stressors including nutrients, climate change, coastal land-use change, and habitat modification. We have developed and demonstrated a geospatial modeling a...

  19. Multiple Positive Solutions for Some Neutral Integral Equatious Modeling Infectious Disease

    Institute of Scientific and Technical Information of China (English)

    ZHAOHua-xiang; SUNXing-wang

    2003-01-01

    By using fixed point index theory of cone mapping and extension method,this paper discusses the existence of multiple positive solution of nonlinear neutral integral equatious modeling infectious dis-ease.

  20. Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration.

    Science.gov (United States)

    Anderson, Ryan M; Bosch, Justin A; Goll, Mary G; Hesselson, Daniel; Dong, P Duc Si; Shin, Donghun; Chi, Neil C; Shin, Chong Hyun; Schlegel, Amnon; Halpern, Marnie; Stainier, Didier Y R

    2009-10-01

    Developmental mechanisms regulating gene expression and the stable acquisition of cell fate direct cytodifferentiation during organogenesis. Moreover, it is likely that such mechanisms could be exploited to repair or regenerate damaged organs. DNA methyltransferases (Dnmts) are enzymes critical for epigenetic regulation, and are used in concert with histone methylation and acetylation to regulate gene expression and maintain genomic integrity and chromosome structure. We carried out two forward genetic screens for regulators of endodermal organ development. In the first, we screened for altered morphology of developing digestive organs, while in the second we screed for the lack of terminally differentiated cell types in the pancreas and liver. From these screens, we identified two mutant alleles of zebrafish dnmt1. Both lesions are predicted to eliminate dnmt1 function; one is a missense mutation in the catalytic domain and the other is a nonsense mutation that eliminates the catalytic domain. In zebrafish dnmt1 mutants, the pancreas and liver form normally, but begin to degenerate after 84 h post fertilization (hpf). Acinar cells are nearly abolished through apoptosis by 100 hpf, though neither DNA replication, nor entry into mitosis is halted in the absence of detectable Dnmt1. However, endocrine cells and ducts are largely spared. Surprisingly, dnmt1 mutants and dnmt1 morpholino-injected larvae show increased capacity for pancreatic beta cell regeneration in an inducible model of pancreatic beta cell ablation. Thus, our data suggest that Dnmt1 is dispensable for pancreatic duct or endocrine cell formation, but not for acinar cell survival. In addition, Dnmt1 may influence the differentiation of pancreatic beta cell progenitors or the reprogramming of cells toward the pancreatic beta cell fate.

  1. Decoupling speed and accuracy in an urgent decision-making task reveals multiple contributions to their trade-off

    Directory of Open Access Journals (Sweden)

    Emilio eSalinas

    2014-04-01

    Full Text Available A key goal in the study of decision making is determining how neural networks involved in perception and motor planning interact to generate a given choice, but this is complicated due to the internal trade-off between speed and accuracy, which confounds their individual contributions. Urgent decisions, however, are special: they may range between random and fully informed, depending on the amount of processing time (or stimulus viewing time available in each trial, but regardless, movement preparation always starts early on. As a consequence, under time pressure it is possible to produce a psychophysical curve that characterizes perceptual performance independently of reaction time, and this, in turn, makes it possible to pinpoint how perceptual information (which requires sensory input modulates motor planning (which does not to guide a choice. Here we review experiments in which, on the basis of this approach, the origin of the speed-accuracy trade-off becomes particularly transparent. Psychophysical, neurophysiological, and modeling results in the `compelled-saccade' task indicate that, during urgent decision making, perceptual information - if and whenever it becomes available - accelerates or decelerates competing motor plans that are already ongoing. This interaction affects both the reaction time and the probability of success in any given trial. In two experiments with reward asymmetries, we find that speed and accuracy can be traded in different amounts and for different reasons, depending on how the particular task contingencies affect specific neural mechanisms related to perception and motor planning. Therefore, from the vantage point of urgent decisions, the speed-accuracy trade-off is not a unique phenomenon tied to a single underlying mechanism, but rather a typical outcome of many possible combinations of internal adjustments within sensory-motor neural circuits.

  2. De novo assembly and characterization of two transcriptomes reveal multiple light-mediated functions in the scallop eye (Bivalvia: Pectinidae.

    Directory of Open Access Journals (Sweden)

    Autum N Pairett

    Full Text Available BACKGROUND: The eye has evolved across 13 separate lineages of molluscs. Yet, there have been very few studies examining the molecular machinary underlying eye function of this group, which is due, in part, to a lack of genomic resources. The scallop (Bivalvia: Pectinidae represents a compeling molluscan model to study photoreception due to its morphologically novel and separately evolved mirror-type eye. We sequenced the adult eye transcriptome of two scallop species to: 1 identify the phototransduction pathway components; 2 identify any additional light detection functions; and 3 test the hypothesis that molluscs possess genes not found in other animal lineages. RESULTS: A total of 3,039 contigs from the bay scallop, Argopecten irradians and 26,395 contigs from the sea scallop, Placopecten magellanicus were produced by 454 sequencing. Targeted BLAST searches and functional annotation using Gene Ontology (GO terms and KEGG pathways identified transcripts from three light detection systems: two phototransduction pathways and the circadian clock, a previously unrecognized function of the scallop eye. By comparing the scallop transcriptomes to molluscan and non-molluscan genomes, we discovered that a large proportion of the transcripts (7,776 sequences may be specific to the scallop lineage. Nearly one-third of these contain transmembrane protein domains, suggesting these unannotated transcripts may be sensory receptors. CONCLUSIONS: Our data provide the most comprehensive transcriptomic resource currently available from a single molluscan eye type. Candidate genes potentially involved in sensory reception were identified, and are worthy of further investigation. This resource, combined with recent phylogenetic and genomic data, provides a strong foundation for future investigations of the function and evolution of molluscan photosensory systems in this morphologically and taxonomically diverse phylum.

  3. Backward probability model using multiple observations of contamination to identify groundwater contamination sources at the Massachusetts Military Reservation

    Science.gov (United States)

    Neupauer, R. M.; Wilson, J. L.

    2005-02-01

    Backward location and travel time probability density functions characterize the possible former locations (or the source location) of contamination that is observed in an aquifer. For an observed contaminant particle the backward location probability density function (PDF) describes its position at a fixed time prior to sampling, and the backward travel time probability density function describes the amount of time required for the particle to travel to the sampling location from a fixed upgradient position. The backward probability model has been developed for a single observation of contamination (e.g., Neupauer and Wilson, 1999). In practical situations, contamination is sampled at multiple locations and times, and these additional data provide information that can be used to better characterize the former position of contamination. Through Bayes' theorem we combine the individual PDFs for each observation to obtain a PDF for multiple observations that describes the possible source locations or release times of all observed contaminant particles, assuming they originated from the same instantaneous point source. We show that the multiple-observation probability density function is the normalized product of the single-observation PDFs. The additional information available from multiple observations reduces the variances of the source location and travel time probability density functions and improves the characterization of the contamination source. We apply the backward probability model to a trichloroethylene (TCE) plume at the Massachusetts Military Reservation (MMR). We use four TCE samples distributed throughout the plume to obtain single-observation and multiple-observation location and travel time PDFs in three dimensions. These PDFs provide information about the possible sources of contamination. Under assumptions that the existing MMR model is properly calibrated and the conceptual model is correct the results confirm the two suspected sources of

  4. Modeling of CMUTs with Multiple Anisotropic Layers and Residual Stress

    DEFF Research Database (Denmark)

    Engholm, Mathias; Thomsen, Erik Vilain

    2014-01-01

    Usually the analytical approach for modeling CMUTs uses the single layer plate equation to obtain the deflection and does not take anisotropy and residual stress into account. A highly accurate model is developed for analytical characterization of CMUTs taking an arbitrary number of layers...... and residual stress into account. Based on the stress-strain relation of each layer and balancing stress resultants and bending moments, a general multilayered anisotropic plate equation is developed for plates with an arbitrary number of layers. The exact deflection profile is calculated for a circular...... clamped plate of anisotropic materials with residual bi-axial stress. From the deflection shape the critical stress for buckling is calculated and by using the Rayleigh-Ritz method the natural frequency is estimated....

  5. A localization model to localize multiple sources using Bayesian inference

    Science.gov (United States)

    Dunham, Joshua Rolv

    Accurate localization of a sound source in a room setting is important in both psychoacoustics and architectural acoustics. Binaural models have been proposed to explain how the brain processes and utilizes the interaural time differences (ITDs) and interaural level differences (ILDs) of sound waves arriving at the ears of a listener in determining source location. Recent work shows that applying Bayesian methods to this problem is proving fruitful. In this thesis, pink noise samples are convolved with head-related transfer functions (HRTFs) and compared to combinations of one and two anechoic speech signals convolved with different HRTFs or binaural room impulse responses (BRIRs) to simulate room positions. Through exhaustive calculation of Bayesian posterior probabilities and using a maximal likelihood approach, model selection will determine the number of sources present, and parameter estimation will result in azimuthal direction of the source(s).

  6. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  7. Field data and numerical modeling: A multiple lines of evidence approach for assessing vapor intrusion exposure risks.

    Science.gov (United States)

    Pennell, Kelly G; Scammell, Madeleine K; McClean, Michael D; Suuberg, Eric M; Moradi, Ali; Roghani, Mohammadyousef; Ames, Jennifer; Friguglietti, Leigh; Indeglia, Paul A; Shen, Rui; Yao, Yijun; Heiger-Bernays, Wendy J

    2016-06-15

    USEPA recommends a multiple lines of evidence approach to make informed decisions at vapor intrusion sites because the vapor intrusion pathway is notoriously difficult to characterize. Our study uses this approach by incorporating groundwater, soil gas, indoor air field measurements and numerical models to evaluate vapor intrusion exposure risks in a Metro-Boston neighborhood known to exhibit lower than anticipated indoor air concentrations based on groundwater concentrations. We collected and evaluated five rounds of field sampling data over the period of one year. Field data results show a steep gradient in soil gas concentrations near the groundwater surface; however as the depth decreases, soil gas concentration gradients also decrease. Together, the field data and the numerical model results suggest that a subsurface feature is limiting vapor transport into indoor air spaces at the study site and that groundwater concentrations are not appropriate indicators of vapor intrusion exposure risks in this neighborhood. This research also reveals the importance of including relevant physical models when evaluating vapor intrusion exposure risks using the multiple lines of evidence approach. Overall, the findings provide insight about how the multiple lines of evidence approach can be used to inform decisions by using field data collected using regulatory-relevant sampling techniques, and a well-established 3-D vapor intrusion model.

  8. Adaptive switching control of discrete time nonlinear systems based on multiple models

    Institute of Scientific and Technical Information of China (English)

    Rui KAN

    2004-01-01

    We use the approach of "optimal" switching to design the adaptive control because the design among multiple models is intuitively more practically feasible than the traditional adaptive control in improving the performances. We prove that for a typical class of nonlinear systems disturbed by random noise, the multiple model adaptive switching control based on WLS(Weighted Least Squares) or projected-LS (Least Squares) is stable and convergent.

  9. Learning probabilistic models of connectivity from multiple spike train data

    OpenAIRE

    2010-01-01

    Neuronal circuits or cell assemblies carry out brain function through complex coordinated firing patterns [1]. Inferring topology of neuronal circuits from simultaneously recorded spike train data is a challenging problem in neuroscience. In this work we present a new class of dynamic Bayesian networks to infer polysynaptic excitatory connectivity between spiking cortical neurons [2]. The emphasis on excitatory networks allows us to learn connectivity models by exploiting fast data mining alg...

  10. A NUI Based Multiple Perspective Variability Modelling CASE Tool

    OpenAIRE

    Bashroush, Rabih

    2010-01-01

    With current trends towards moving variability from hardware to \\ud software, and given the increasing desire to postpone design decisions as much \\ud as is economically feasible, managing the variability from requirements \\ud elicitation to implementation is becoming a primary business requirement in the \\ud product line engineering process. One of the main challenges in variability \\ud management is the visualization and management of industry size variability \\ud models. In this demonstrat...

  11. Modeling water demand when households have multiple sources of water

    Science.gov (United States)

    Coulibaly, Lassina; Jakus, Paul M.; Keith, John E.

    2014-07-01

    A significant portion of the world's population lives in areas where public water delivery systems are unreliable and/or deliver poor quality water. In response, people have developed important alternatives to publicly supplied water. To date, most water demand research has been based on single-equation models for a single source of water, with very few studies that have examined water demand from two sources of water (where all nonpublic system water sources have been aggregated into a single demand). This modeling approach leads to two outcomes. First, the demand models do not capture the full range of alternatives, so the true economic relationship among the alternatives is obscured. Second, and more seriously, economic theory predicts that demand for a good becomes more price-elastic as the number of close substitutes increases. If researchers artificially limit the number of alternatives studied to something less than the true number, the price elasticity estimate may be biased downward. This paper examines water demand in a region with near universal access to piped water, but where system reliability and quality is such that many alternative sources of water exist. In extending the demand analysis to four sources of water, we are able to (i) demonstrate why households choose the water sources they do, (ii) provide a richer description of the demand relationships among sources, and (iii) calculate own-price elasticity estimates that are more elastic than those generally found in the literature.

  12. An architecture model for multiple disease management information systems.

    Science.gov (United States)

    Chen, Lichin; Yu, Hui-Chu; Li, Hao-Chun; Wang, Yi-Van; Chen, Huang-Jen; Wang, I-Ching; Wang, Chiou-Shiang; Peng, Hui-Yu; Hsu, Yu-Ling; Chen, Chi-Huang; Chuang, Lee-Ming; Lee, Hung-Chang; Chung, Yufang; Lai, Feipei

    2013-04-01

    Disease management is a program which attempts to overcome the fragmentation of healthcare system and improve the quality of care. Many studies have proven the effectiveness of disease management. However, the case managers were spending the majority of time in documentation, coordinating the members of the care team. They need a tool to support them with daily practice and optimizing the inefficient workflow. Several discussions have indicated that information technology plays an important role in the era of disease management. Whereas applications have been developed, it is inefficient to develop information system for each disease management program individually. The aim of this research is to support the work of disease management, reform the inefficient workflow, and propose an architecture model that enhance on the reusability and time saving of information system development. The proposed architecture model had been successfully implemented into two disease management information system, and the result was evaluated through reusability analysis, time consumed analysis, pre- and post-implement workflow analysis, and user questionnaire survey. The reusability of the proposed model was high, less than half of the time was consumed, and the workflow had been improved. The overall user aspect is positive. The supportiveness during daily workflow is high. The system empowers the case managers with better information and leads to better decision making.

  13. Atmospheric Climate Model Experiments Performed at Multiple Horizontal Resolutions

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, T; Bala, G; Gleckler, P; Lobell, D; Mirin, A; Maxwell, R; Rotman, D

    2007-12-21

    This report documents salient features of version 3.3 of the Community Atmosphere Model (CAM3.3) and of three climate simulations in which the resolution of its latitude-longitude grid was systematically increased. For all these simulations of global atmospheric climate during the period 1980-1999, observed monthly ocean surface temperatures and sea ice extents were prescribed according to standard Atmospheric Model Intercomparison Project (AMIP) values. These CAM3.3 resolution experiments served as control runs for subsequent simulations of the climatic effects of agricultural irrigation, the focus of a Laboratory Directed Research and Development (LDRD) project. The CAM3.3 model was able to replicate basic features of the historical climate, although biases in a number of atmospheric variables were evident. Increasing horizontal resolution also generally failed to ameliorate the large-scale errors in most of the climate variables that could be compared with observations. A notable exception was the simulation of precipitation, which incrementally improved with increasing resolution, especially in regions where orography plays a central role in determining the local hydroclimate.

  14. A multiple time-scale model for TCP bandwidth sharing under user heterogeneity

    NARCIS (Netherlands)

    Abendroth, D.; Berg, J.L. van den; Mandjes, M.

    2005-01-01

    Building on the vast body of existing TCP models, we develop a novel versatile model that explicitly captures user heterogeneity, and takes into consideration dynamics at both the packet level and the flow level. It is described how the resulting multiple time-scale model can be numerically evaluate

  15. The common marmoset as an indispensable animal model for immunotherapy development in multiple sclerosis

    NARCIS (Netherlands)

    Kap, Yolanda S.; Jagessar, S. Anwar; Dunham, Jordon; 't Hart, Bert A.

    2016-01-01

    New drugs often fail in the translation from the rodent experimental autoimmune encephalomyelitis (EAE) model to human multiple sclerosis (MS). Here, we present the marmoset EAE model as an indispensable model for translational research into MS. The genetic heterogeneity of this species and lifelong

  16. Testing effect of a drug using multiple nested models for the dose–response

    DEFF Research Database (Denmark)

    Baayen, C.; Hougaard, P.; Pipper, C. B.

    2015-01-01

    of the assumed dose–response model. Bretz et al. (2005, Biometrics 61, 738–748) suggested a combined approach, which selects one or more suitable models from a set of candidate models using a multiple comparison procedure. The method initially requires a priori estimates of any non-linear parameters...

  17. Exacting predictions by cybernetic model confirmed experimentally: steady state multiplicity in the chemostat.

    Science.gov (United States)

    Kim, Jin Il; Song, Hyun-Seob; Sunkara, Sunil R; Lali, Arvind; Ramkrishna, Doraiswami

    2012-01-01

    We demonstrate strong experimental support for the cybernetic model based on maximizing carbon uptake rate in describing the microorganism's regulatory behavior by verifying exacting predictions of steady state multiplicity in a chemostat. Experiments with a feed mixture of glucose and pyruvate show multiple steady state behavior as predicted by the cybernetic model. When multiplicity occurs at a dilution (growth) rate, it results in hysteretic behavior following switches in dilution rate from above and below. This phenomenon is caused by transient paths leading to different steady states through dynamic maximization of the carbon uptake rate. Thus steady state multiplicity is a manifestation of the nonlinearity arising from cybernetic mechanisms rather than of the nonlinear kinetics. The predicted metabolic multiplicity would extend to intracellular states such as enzyme levels and fluxes to be verified in future experiments.

  18. Multiple instance learning for hidden Markov models: application to landmine detection

    Science.gov (United States)

    Bolton, Jeremy; Yuksel, Seniha Esen; Gader, Paul

    2013-06-01

    Multiple instance learning is a recently researched learning paradigm in machine intelligence which operates under conditions of uncertainty. A Multiple Instance Hidden Markov Model (MI-HMM) is investigated with applications to landmine detection using ground penetrating radar data. Without introducing any additional parameters, the MI-HMM provides an elegant and simple way to learn the parameters of an HMM in a multiple instance framework. The efficacy of the model is shown on a real landmine dataset. Experiments on the landmine dataset show that MI-HMM learning is effective.

  19. Phase-field model of isothermal solidification with multiple grain growth

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Wang Zhi-Ping; Zhu Chang-Sheng; Lu Yang

    2009-01-01

    This paper develops a new phase-field model for equiaxed dendrite growth of multiple grains in multicomponent alloys based on the Ginzberg-Landau theory and phase-field model of a single grain. Taking Al-Cu and Al-Cu-Mg alloys for example, it couples the concentration field and simulates the dendrite growth process of multiple grains during isothermal solidification. The result of the simulation shows dendrite competitive growth of multiple grains, and is reapplied to the process of dendrite growth in practical solidification.

  20. ADDITIVE-MULTIPLICATIVE MODEL FOR RISK ESTIMATION IN THE PRODUCTION OF ROCKET AND SPACE TECHNICS

    Directory of Open Access Journals (Sweden)

    Orlov A. I.

    2014-10-01

    Full Text Available For the first time we have developed a general additive-multiplicative model of the risk estimation (to estimate the probabilities of risk events. In the two-level system in the lower level the risk estimates are combined additively, on the top – in a multiplicative way. Additive-multiplicative model was used for risk estimation for (1 implementation of innovative projects at universities (with external partners, (2 the production of new innovative products, (3 the projects for creation of rocket and space equipmen

  1. Multiple Discrete Endogenous Variables in Weakly-Separable Triangular Models

    Directory of Open Access Journals (Sweden)

    Sung Jae Jun

    2016-02-01

    Full Text Available We consider a model in which an outcome depends on two discrete treatment variables, where one treatment is given before the other. We formulate a three-equation triangular system with weak separability conditions. Without assuming assignment is random, we establish the identification of an average structural function using two-step matching. We also consider decomposing the effect of the first treatment into direct and indirect effects, which are shown to be identified by the proposed methodology. We allow for both of the treatment variables to be non-binary and do not appeal to an identification-at-infinity argument.

  2. Convex Combination of Multiple Statistical Models with Application to VAD

    DEFF Research Database (Denmark)

    Petsatodis, Theodoros; Boukis, Christos; Talantzis, Fotios

    2011-01-01

    This paper proposes a robust Voice Activity Detector (VAD) based on the observation that the distribution of speech captured with far-field microphones is highly varying, depending on the noise and reverberation conditions. The proposed VAD employs a convex combination scheme comprising three...... statistical distributions - a Gaussian, a Laplacian, and a two-sided Gamma - to effectively model captured speech. This scheme shows increased ability to adapt to dynamic acoustic environments. The contribution of each distribution to this convex combination is automatically adjusted based on the statistical...

  3. Analysis of an incomplete longitudinal composite variable using a marginalized random effects model and multiple imputation.

    Science.gov (United States)

    Gosho, Masahiko; Maruo, Kazushi; Ishii, Ryota; Hirakawa, Akihiro

    2016-11-16

    The total score, which is calculated as the sum of scores in multiple items or questions, is repeatedly measured in longitudinal clinical studies. A mixed effects model for repeated measures method is often used to analyze these data; however, if one or more individual items are not measured, the method cannot be directly applied to the total score. We develop two simple and interpretable procedures that infer fixed effects for a longitudinal continuous composite variable. These procedures consider that the items that compose the total score are multivariate longitudinal continuous data and, simultaneously, handle subject-level and item-level missing data. One procedure is based on a multivariate marginalized random effects model with a multiple of Kronecker product covariance matrices for serial time dependence and correlation among items. The other procedure is based on a multiple imputation approach with a multivariate normal model. In terms of the type-1 error rate and the bias of treatment effect in total score, the marginalized random effects model and multiple imputation procedures performed better than the standard mixed effects model for repeated measures analysis with listwise deletion and single imputations for handling item-level missing data. In particular, the mixed effects model for repeated measures with listwise deletion resulted in substantial inflation of the type-1 error rate. The marginalized random effects model and multiple imputation methods provide for a more efficient analysis by fully utilizing the partially available data, compared to the mixed effects model for repeated measures method with listwise deletion.

  4. Parametric bootstrap methods for testing multiplicative terms in GGE and AMMI models.

    Science.gov (United States)

    Forkman, Johannes; Piepho, Hans-Peter

    2014-09-01

    The genotype main effects and genotype-by-environment interaction effects (GGE) model and the additive main effects and multiplicative interaction (AMMI) model are two common models for analysis of genotype-by-environment data. These models are frequently used by agronomists, plant breeders, geneticists and statisticians for analysis of multi-environment trials. In such trials, a set of genotypes, for example, crop cultivars, are compared across a range of environments, for example, locations. The GGE and AMMI models use singular value decomposition to partition genotype-by-environment interaction into an ordered sum of multiplicative terms. This article deals with the problem of testing the significance of these multiplicative terms in order to decide how many terms to retain in the final model. We propose parametric bootstrap methods for this problem. Models with fixed main effects, fixed multiplicative terms and random normally distributed errors are considered. Two methods are derived: a full and a simple parametric bootstrap method. These are compared with the alternatives of using approximate F-tests and cross-validation. In a simulation study based on four multi-environment trials, both bootstrap methods performed well with regard to Type I error rate and power. The simple parametric bootstrap method is particularly easy to use, since it only involves repeated sampling of standard normally distributed values. This method is recommended for selecting the number of multiplicative terms in GGE and AMMI models. The proposed methods can also be used for testing components in principal component analysis.

  5. Emergence of multiple ocean ecosystem drivers in a large ensemble suite with an earth system model

    Directory of Open Access Journals (Sweden)

    K. B. Rodgers

    2014-12-01

    Full Text Available Marine ecosystems are increasingly impacted by human-induced changes. Ocean ecosystem drivers – including warming, acidification, deoxygenation and perturbations to biological productivity – can co-occur in space and time, but detecting their trends is complicated by the presence of noise associated with natural variability in the climate system. Here we use Large Initial-Condition Ensemble Simulations with a comprehensive Earth System Model under a historical/RCP8.5 pathway over 1950–2100 to consider emergence characteristics for the four individual and combined drivers. Using a one-standard deviation (67% confidence threshold of signal-to-noise to define emergence with a 30 yr trend window, we show that ocean acidification emerges much earlier than other drivers, namely during the 20th century over most of the global ocean. For biological productivity, the anthropogenic signal does not emerge from the noise over most of the global ocean before the end of the 21st century. The early emergence pattern for sea surface temperature in low latitudes is reversed from that of subsurface oxygen inventories, where emergence occurs earlier in the Southern Ocean. For the combined multiple-driver field, 41% of the global ocean exhibits emergence for the 2005–2014 period, and 63% for the 2075–2084 period. The combined multiple-driver field reveals emergence patterns by the end of this century that are relatively high over much of the Southern Ocean, North Pacific, and Atlantic, but relatively low over the tropics and the South Pacific. In regions with pronounced emergence characteristics, marine ecosystems can be expected to be pushed outside of their comfort zone determined by the degree of natural background variability to which they are adapted. The results here thus have implications not only for optimization of the ocean observing system, but also for risk assessment and mitigation strategies.

  6. A multiple flux-tube solar wind model

    CERN Document Server

    Pinto, Rui F

    2016-01-01

    We present a new model, MULTI-VP, that computes the three-dimensional structure of the solar wind which includes the chromosphere, the transition region, and the corona and low heliosphere. MULTI- VP calculates a large ensemble of wind profiles flowing along open magnetic field-lines which sample the whole three-dimensional atmosphere or, alternatively, on a given region of interest. The radial domain starts from the photosphere and extends, typically, to about 30 $R_{sun}$ . The elementary uni-dimensional wind solutions are based on a mature numerical scheme which was adapted in order to accept any flux-tube geometry. We discuss here the first results obtained with this model. We use Potential Field Source-Surface (PFSS) extrapolations of magnetograms from the Wilcox Solar Observatory (WSO) to determine the structure of the background magnetic field. Our results support the hypothesis that the geometry of the magnetic flux-tubes in the lower corona controls the distribution of slow and fast wind flows. The i...

  7. Multiple-Scale Geomechanical Models for Thermal Spallation Drilling.

    Science.gov (United States)

    Lomov, I.; Walsh, S. D.; Roberts, J. J.

    2011-12-01

    Widespread adoption of geothermal energy will require access to deeply buried geothermal sources in granitic basement rocks at high temperatures and pressures. Exploiting these resources necessitates novel methods for drilling, stimulation, and maintenance, under operating conditions difficult or impossible to test in laboratory settings. Physically rigorous numerical modeling tools are vital to highlight potential risks, guide process optimization and reduce the uncertainties involved in these developing technologies. In this presentation, we discuss a numerical modeling effort investigating the multiscale mechanics of thermal spallation drilling (TSD) - a technique in which rock is fragmented into small flakes by a high temperature fluid jet. This process encompasses interconnected phenomena on several length and time scales: from system-scale fluid dynamics to grain-scale thermomechanics of spallation. Here we describe how these disperate scales are simulated using GEODYN, a parallel Eulerian compressible solid and fluid dynamics code with adaptive mesh refinement (AMR) capabilities. GEODYN is able to simulate materials under extremely large deformations, resolve details of wave propagation within grains, and uses a continuum damage mechanics approach to represent fracture. We will present results from both system- and grain-scale simulations describing the transfer of heat from the high temperature jet to the rock face, and the effect of grain-scale properties such as incipient flaw distribution, grain size and grain size distribution, heat flux, applied temperature and material heterogeneity on the onset of spallation. Detailed computer modeling helps to address several of the uncertainties surrounding TSD: 1) What rock compositions are drillable with TSD? 2) How do grain size and grain size distribution affect TSD and drilling rates? 3) What combination of macroscopic (Poisson ratio, heat capacity and thermal conductivity) and microscopic (flaw distribution

  8. Music genre classification via likelihood fusion from multiple feature models

    Science.gov (United States)

    Shiu, Yu; Kuo, C.-C. J.

    2005-01-01

    Music genre provides an efficient way to index songs in a music database, and can be used as an effective means to retrieval music of a similar type, i.e. content-based music retrieval. A new two-stage scheme for music genre classification is proposed in this work. At the first stage, we examine a couple of different features, construct their corresponding parametric models (e.g. GMM and HMM) and compute their likelihood functions to yield soft classification results. In particular, the timbre, rhythm and temporal variation features are considered. Then, at the second stage, these soft classification results are integrated to result in a hard decision for final music genre classification. Experimental results are given to demonstrate the performance of the proposed scheme.

  9. Electronic Commerce Success Model: A Search for Multiple Criteria

    Directory of Open Access Journals (Sweden)

    Didi Achjari

    2004-01-01

    Full Text Available The current study attempts to develop and examine framework of e-commerce success. In order to obtain comprehensive and robust measures, the framework accomodates key factors that are identified in the literature concerning the success of electronic commerce. The structural model comprises of four exogenous variables (Internal Driver, Internal Impediment, External Driver and Exgternal Impediment and one endogenous variable (Electornic Commerce Success eith 24 observed variables. The study that was administered within large Australian companies using questionaire survey concluded that benefits for both internal organization and external parties from the use of e-commerce were the main factor tro predict perceived and/or expected success of electronic commerce.

  10. The impact of ignoring multiple membership data structures in multilevel models.

    Science.gov (United States)

    Chung, Hyewon; Beretvas, S Natasha

    2012-05-01

    This study compared the use of the conventional multilevel model (MM) with that of the multiple membership multilevel model (MMMM) for handling multiple membership data structures. Multiple membership data structures are commonly encountered in longitudinal educational data sets in which, for example, mobile students are members of more than one higher-level unit (e.g., school). While the conventional MM requires the user either to delete mobile students' data or to ignore prior schools attended, MMMM permits inclusion of mobile students' data and models the effect of all schools attended on student outcomes. The simulation study identified underestimation of the school-level predictor coefficient, as well as underestimation of the level-two variance component with corresponding overestimation of the level-one variance when multiple membership data structures were ignored. Results are discussed along with limitations and ideas for future MMMM methodological research as well as implications for applied researchers.

  11. Should researchers use single indicators, best indicators, or multiple indicators in structural equation models?

    Directory of Open Access Journals (Sweden)

    Hayduk Leslie A

    2012-10-01

    Full Text Available Abstract Background Structural equation modeling developed as a statistical melding of path analysis and factor analysis that obscured a fundamental tension between a factor preference for multiple indicators and path modeling’s openness to fewer indicators. Discussion Multiple indicators hamper theory by unnecessarily restricting the number of modeled latents. Using the few best indicators – possibly even the single best indicator of each latent – encourages development of theoretically sophisticated models. Additional latent variables permit stronger statistical control of potential confounders, and encourage detailed investigation of mediating causal mechanisms. Summary We recommend the use of the few best indicators. One or two indicators are often sufficient, but three indicators may occasionally be helpful. More than three indicators are rarely warranted because additional redundant indicators provide less research benefit than single indicators of additional latent variables. Scales created from multiple indicators can introduce additional problems, and are prone to being less desirable than either single or multiple indicators.

  12. Robotic and mathematical modeling reveal general principles of appendage control and coordination in terrestrial locomotion

    Science.gov (United States)

    McInroe, Benjamin; Astley, Henry; Gong, Chaohui; Kawano, Sandy; Schiebel, Perrin; Choset, Howie; Goldman, Daniel I.

    The transition from aquatic to terrestrial life presented new challenges to early walkers, necessitating robust locomotion on complex, flowable substrates (e.g. sand, mud). Locomotion on such substrates is sensitive to limb morphology and kinematics. Although early walker morphologies are known, principles of appendage control remain elusive. To reveal limb control strategies that facilitated the invasion of land, we study both robotic and mathematical models. Robot experiments show that an active tail is critical for robust locomotion on granular media, enabling locomotion even with poor foot placement and limited ability to lift the body. Using a granular resistive force theory model, we construct connection vector fields that reveal how appendage coordination and terrain inclination impact locomotor performance. This model replicates experimental results, showing that moving limbs/tail in phase is most effective (suggesting a locomotor template). Varying limb trajectories and contacts, we find gaits for which tail use can be neutral or harmful, suggesting limb-tail coordination to be a nontrivial aspect of locomotion. Our findings show that robot experiments coupled with geometric mechanics provide a general framework to reveal principles of robust terrestrial locomotion. This work was supported by NSF PoLS.

  13. Modeling individual subtests of the WAIS IV with multiple latent factors.

    Directory of Open Access Journals (Sweden)

    Dennis J McFarland

    Full Text Available Performance on a cognitive test can be viewed either as measuring a unitary function or as reflecting the operation of multiple factors. Individual subtests in batteries designed to measure human abilities are commonly modeled as a single latent factor. Several latent factors are then used to model groups of subtests. However these latent factors are not independent as they are related through hierarchical or oblique structures. As a result, the simple structure of subtest performance results in complex latent factors. The present study used structural equation modeling to evaluate several multidimensional models of the Wechsler Adult Intelligence Scales-fourth edition (WAIS-IV subtests. Multidimensional models of subtest performance provided better model fit as compared to several previously proposed one dimensional models. These multidimensional models also generalized well to new samples of populations differing in age from that used to estimate the model parameters. Overall these results show that models that describe subtests as multidimensional functions of uncorrelated factors provided a better fit to the WAIS-IV correlations than models that describe subtests as one dimensional functions of correlated factors. There appears to be a trade-off in modeling subtests as one dimensional and modeling with homogeneous latent traits. More consideration should be given to models that include multiple uncorrelated latent factors as determinants of the performance on a given subtest. These results support the view that performance on any given cognitive test is potentially the result of multiple factors. Simple structure may be too simple.

  14. Modeling individual subtests of the WAIS IV with multiple latent factors.

    Science.gov (United States)

    McFarland, Dennis J

    2013-01-01

    Performance on a cognitive test can be viewed either as measuring a unitary function or as reflecting the operation of multiple factors. Individual subtests in batteries designed to measure human abilities are commonly modeled as a single latent factor. Several latent factors are then used to model groups of subtests. However these latent factors are not independent as they are related through hierarchical or oblique structures. As a result, the simple structure of subtest performance results in complex latent factors. The present study used structural equation modeling to evaluate several multidimensional models of the Wechsler Adult Intelligence Scales-fourth edition (WAIS-IV) subtests. Multidimensional models of subtest performance provided better model fit as compared to several previously proposed one dimensional models. These multidimensional models also generalized well to new samples of populations differing in age from that used to estimate the model parameters. Overall these results show that models that describe subtests as multidimensional functions of uncorrelated factors provided a better fit to the WAIS-IV correlations than models that describe subtests as one dimensional functions of correlated factors. There appears to be a trade-off in modeling subtests as one dimensional and modeling with homogeneous latent traits. More consideration should be given to models that include multiple uncorrelated latent factors as determinants of the performance on a given subtest. These results support the view that performance on any given cognitive test is potentially the result of multiple factors. Simple structure may be too simple.

  15. Tracking multiple people under occlusion and across cameras using probabilistic models

    Institute of Scientific and Technical Information of China (English)

    Xuan-he WANG; Ji-lin LIU

    2009-01-01

    Tracking multiple people under occlusion and across cameras is a challenging question for discussion. Furthermore,the cameras in this study are used to extend the field of view, which are distinguished from the same field of view. Such correspondence between multiple cameras is a burgeoning research subject in the area of computer vision. This paper effectively solves the problems of tracking multiple people who pass from one camera to another and segmenting people under occlusion using probabilistic models. The probabilistic models are composed of blob model, motion model and color model, which make the most of the space, motion and color information. First, we present a color model that uses maximum likelihood estimation based on non-parametric kernel density estimation. Second, we introduce a blob model based on mean shift, which segments the body into many regions according to the color of each person in order to spatially localize the color features corresponding to the way people are dressed. Clothes can be any mixture of colors. Third, we bring forward a motion model based on statistical probability which indicates the movement position of the same person between two successive frames in a single camera. Finally, we effectively unify the three models into a general probabilistic model and attain a maximization likelihood probability image, which is used to segment the foreground region under occlusion and to match people across multiple cameras.

  16. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  17. A test of the multiple connections model of reading acquisition.

    Science.gov (United States)

    Berninger, V W; Chen, A C; Abbott, R D

    1988-10-01

    Within the framework of Society of Mind Theory (Minsky, 1986), learning to read is conceptualized as a process of creating new communication links or neural connections between an existing visual society and an existing linguistic society. Four visual-linguistic connections may become functional: letter-phonemic code, whole word-semantic code, whole word-name code, letter sequence-aural syllabic code. The hypothesis was tested that more than one of these visual-linguistic connections must be taken into account in predicting reading achievement. Results showed that the combination of the composite letter-phoneme variable and the composite whole word-semantic code variable accounted for significantly more variance in oral reading than did either single variable at the end of the first grade. Groups with large absolute discrepancy (1 or more standard scores) or small absolute discrepancy (1/3 standard score or less) on corresponding visual and linguistic skills differed significantly in both oral (whole word-semantic code composite) and silent reading (whole word-semantic code and letter sequence-aural syllabic code composites). There was a relationship between the number of large discrepancies and reading achievement. Results are discussed in reference to neuropsychological models of connectionism (Rumelhart & McClelland, 1986) and working brain systems (Luria, 1973).

  18. Gear Defect Modeling of a Multiple-Stage Gear Train

    Directory of Open Access Journals (Sweden)

    Andrew Sommer

    2011-01-01

    Full Text Available This study demonstrates the transient and steady state dynamic loading on teeth within a two-stage gear transmission arising from backlash and geometric manufacturing errors by utilizing a nonlinear multibody dynamics software model. Backlash between gear teeth which is essential to provide better lubrication on tooth surfaces and to eliminate interference is included as a defect and a necessary part of transmission design. Torsional vibration is shown to cause teeth separation and double-sided impacts in unloaded and lightly loaded gearing drives. Vibration and impact force distinctions between backlash and combinations of transmission errors are demonstrated under different initial velocities and load conditions. The backlash and manufacturing errors in the first stage of the gear train are distinct from those of the second stage. By analyzing the signal at a location between the two stages, the mutually affected impact forces are observed from different gear pairs, a phenomenon not observed from single pair of gears. Frequency analysis shows the appearance of side band modulations as well as harmonics of the gear mesh frequency. A joint time-frequency response analysis during startup illustrates the manner in which contact forces increase during acceleration.

  19. Sensor management for multiple target tracking with heterogeneous sensor models

    Science.gov (United States)

    Williams, Jason L.; Fisher, John W., III; Willsky, Alan S.

    2006-05-01

    Modern sensors are able to rapidly change mode of operation and steer between physically separated objects. While control of such sensors over a rolling planning horizon can be formulated as a dynamic program, the optimal solution is inevitably intractable. In this paper, we consider the control problem under a restricted family of policies and show that the essential sensor control trade-offs are still captured. The advantage of this approach is that one can obtain the optimal policy within the restricted class in a tractable fashion, in this case by using the auction algorithm. The approach is well-suited for problems in which a single sensor (or group of sensors) is being used to track many targets using a heterogeneous sensor model, i.e., where the quality of observations varies with object state, such as due to obscuration. Our algorithm efficiently weighs the rewards achievable by observing each target at each time to find the best sensor plan within the restricted set. We extend this approach using a roll-out algorithm, to handle additional cases such as when observations take different amounts of time to complete.

  20. Nanostructure Determination by Co-Refining Models to Multiple Datasets

    Energy Technology Data Exchange (ETDEWEB)

    Billinge, Simon

    2011-05-31

    The results of the work are contained in the publications resulting from the grant (which are listed below). Here I summarize the main findings from the last period of the award, 2006-2007: • Published a paper in Science with Igor Levin outlining the “Nanostructure Problem”, our inability to solve structure at the nanoscale. • Published a paper in Nature demonstrating the first ever ab-initio structure determination of a nanoparticle from atomic pair distribution function (PDF) data. • Published one book and 3 overview articles on PDF methods and the nanostructure problem. • Completed a project that sought to find a structural response to the presence of the so-called “intermediate phase” in network glasses which appears close to the rigidity percolation threshold in these systems. The main result was that we did not see convincing evidence for this, which drew into doubt the idea that GexSe1-x glasses were a model system exhibiting rigidity percolation.

  1. Disaggregate Traffic Mode Choice Model Based on Combination of Revealed and Stated Preference Data

    Institute of Scientific and Technical Information of China (English)

    JIAO Pengpeng; LU Huapu; YANG Lang

    2006-01-01

    The conventional traffic demand forecasting methods based on revealed preference (RP) data are not able to predict the modal split. Passengers' stated intentions are indispensable for modal split forecasting and evaluation of new traffic modes. This paper analyzed the biases and errors included in stated preference data, put forward the new stochastic utility functions, and proposed an unbiased disaggregate model and its approximate model based on the combination of RP and stated preference (SP) data, with analysis of the parameter estimation algorithm. The model was also used to forecast rail transit passenger volumes to the Beijing Capital International Airport and the shift ratios from current traffic modes to rail transit. Experimental results show that the model can greatly increase forecasting accuracy of the modal split ratio of current traffic modes and can accurately forecast the shift ratios from current modes to the new mode.

  2. QTL mapping in multiple populations and development stages reveals dynamic quantitative trait loci for fruit size in cucumbers of different market classes.

    Science.gov (United States)

    Weng, Yiqun; Colle, Marivi; Wang, Yuhui; Yang, Luming; Rubinstein, Mor; Sherman, Amir; Ophir, Ron; Grumet, Rebecca

    2015-09-01

    QTL analysis in multi-development stages with different QTL models identified 12 consensus QTLs underlying fruit elongation and radial growth presenting a dynamic view of genetic control of cucumber fruit development. Fruit size is an important quality trait in cucumber (Cucumis sativus L.) of different market classes. However, the genetic and molecular basis of fruit size variations in cucumber is not well understood. In this study, we conducted QTL mapping of fruit size in cucumber using F2, F2-derived F3 families and recombinant inbred lines (RILs) from a cross between two inbred lines Gy14 (North American picking cucumber) and 9930 (North China fresh market cucumber). Phenotypic data of fruit length and diameter were collected at three development stages (anthesis, immature and mature fruits) in six environments over 4 years. QTL analysis was performed with three QTL models including composite interval mapping (CIM), Bayesian interval mapping (BIM), and multiple QTL mapping (MQM). Twenty-nine consistent and distinct QTLs were detected for nine traits from multiple mapping populations and QTL models. Synthesis of information from available fruit size QTLs allowed establishment of 12 consensus QTLs underlying fruit elongation and radial growth, which presented a dynamic view of genetic control of cucumber fruit development. Results from this study highlighted the benefits of QTL analysis with multiple QTL models and different mapping populations in improving the power of QTL detection. Discussion was presented in the context of domestication and diversifying selection of fruit length and diameter, marker-assisted selection of fruit size, as well as identification of candidate genes for fruit size QTLs in cucumber.

  3. Persistent search in single and multiple confined domains: a velocity-jump process model

    Science.gov (United States)

    Poll, Daniel B.; Kilpatrick, Zachary P.

    2016-05-01

    We analyze velocity-jump process models of persistent search for a single target on a bounded domain. The searcher proceeds along ballistic trajectories and is absorbed upon collision with the target boundary. When reaching the domain boundary, the searcher chooses a random direction for its new trajectory. For circular domains and targets, we can approximate the mean first passage time (MFPT) using a Markov chain approximation of the search process. Our analysis and numerical simulations reveal that the time to find the target decreases for targets closer to the domain boundary. When there is a small probability of direction-switching within the domain, we find the time to find the target decreases slightly with the turning probability. We also extend our exit time analysis to the case of partitioned domains, where there is a single target within one of multiple disjoint subdomains. Given an average time of transition between domains , we find that the optimal rate of transition that minimizes the time to find the target obeys {β\\text{min}}\\propto 1/\\sqrt .

  4. Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

    Directory of Open Access Journals (Sweden)

    Jatin Narula

    2010-05-01

    Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

  5. Power-Law Modeling of Cancer Cell Fates Driven by Signaling Data to Reveal Drug Effects

    Science.gov (United States)

    Zhang, Fan; Wu, Min; Kwoh, Chee Keong; Zheng, Jie

    2016-01-01

    Extracellular signals are captured and transmitted by signaling proteins inside a cell. An important type of cellular responses to the signals is the cell fate decision, e.g., apoptosis. However, the underlying mechanisms of cell fate regulation are still unclear, thus comprehensive and detailed kinetic models are not yet available. Alternatively, data-driven models are promising to bridge signaling data with the phenotypic measurements of cell fates. The traditional linear model for data-driven modeling of signaling pathways has its limitations because it assumes that the a cell fate is proportional to the activities of signaling proteins, which is unlikely in the complex biological systems. Therefore, we propose a power-law model to relate the activities of all the measured signaling proteins to the probabilities of cell fates. In our experiments, we compared our nonlinear power-law model with the linear model on three cancer datasets with phosphoproteomics and cell fate measurements, which demonstrated that the nonlinear model has superior performance on cell fates prediction. By in silico simulation of virtual protein knock-down, the proposed model is able to reveal drug effects which can complement traditional approaches such as binding affinity analysis. Moreover, our model is able to capture cell line specific information to distinguish one cell line from another in cell fate prediction. Our results show that the power-law data-driven model is able to perform better in cell fate prediction and provide more insights into the signaling pathways for cancer cell fates than the linear model. PMID:27764199

  6. Models of production runs for multiple products in flexible manufacturing system

    Directory of Open Access Journals (Sweden)

    Ilić Oliver

    2011-01-01

    Full Text Available How to determine economic production runs (EPR for multiple products in flexible manufacturing systems (FMS is considered in this paper. Eight different although similar, models are developed and presented. The first four models are devoted to the cases when no shortage is allowed. The other four models are some kind of generalization of the previous ones when shortages may exist. The numerical examples are given as the illustration of the proposed models.

  7. Using multiple group modeling to test moderators in meta-analysis.

    Science.gov (United States)

    Schoemann, Alexander M

    2016-12-01

    Meta-analysis is a popular and flexible analysis that can be fit in many modeling frameworks. Two methods of fitting meta-analyses that are growing in popularity are structural equation modeling (SEM) and multilevel modeling (MLM). By using SEM or MLM to fit a meta-analysis researchers have access to powerful techniques associated with SEM and MLM. This paper details how to use one such technique, multiple group analysis, to test categorical moderators in meta-analysis. In a multiple group meta-analysis a model is fit to each level of the moderator simultaneously. By constraining parameters across groups any model parameter can be tested for equality. Using multiple groups to test for moderators is especially relevant in random-effects meta-analysis where both the mean and the between studies variance of the effect size may be compared across groups. A simulation study and the analysis of a real data set are used to illustrate multiple group modeling with both SEM and MLM. Issues related to multiple group meta-analysis and future directions for research are discussed. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Storm-time Distortion of the Near Magnetosphere as Revealed by Data-Based Models

    Science.gov (United States)

    Sitnov, M. I.; Tsyganenko, N. A.

    2007-05-01

    An overview will be given of recent progress in the empirical modeling of the geomagnetic field, focused on the storm-time reconfiguration of the inner magnetosphere. Data-based modeling still remains one of primary techniques for representing and forecasting the structure and dynamics of the inner magnetosphere, an extremely hard task for the first-principle approaches. The storm-time evolution of the inner geomagnetic field was quantitatively modeled by Tsyganenko, Singer, and Kasper [2003], where it was shown for the first time that a global dramatic distortion of the magnetic field during strong storms could penetrate as deep as to only R ~ 3RE. The dynamical aspects of storm-time magnetic field distortions were further elaborated in the TS05 model [Tsyganenko and Sitnov, 2005]. It was shown, in particular, that the magnetospheric response to the solar wind loading is drastically different for major current systems (ring, tail, and field-aligned currents), with the fastest response for field-aligned currents and the slowest for the symmetrical ring current. Finally, to resolve the complex spatial structure of storm-time magnetic field distortions Tsyganenko and Sitnov [2007] elaborated a new model with a high-resolution extensible approximation for the field of equatorial currents combined with a flexible field-aligned current module. The new model was fitted to a new database of space magnetometer data from Geotail, Polar, Cluster, IMP-8, and Goes-8,-9,-10, and -12, as well as concurrent solar wind and IMF data, spanning more than a decade (1995-2005). The new high-resolution magnetic field modeling revealed many interesting effects that were conjectured earlier based on other (largely indirect) methods, such as the pile-up of the magnetic flux near the magnetopause for northward IMF and the strong erosion/depression of the dayside field during intervals of southward IMF. It also revealed a dramatic difference between the global configurations of equatorial

  9. Multiple Genome Comparison within a Bacterial Species Reveals a Unit of Evolution Spanning Two Adjacent Genes in a Tandem Paralog Cluster

    Science.gov (United States)

    Tsuru, Takeshi

    2008-01-01

    It has been assumed that an open reading frame (ORF) represents a unit of gene evolution as well as a unit of gene expression and function. In the present work, we report a case in which a unit comprising the 3′ region of an ORF linked to a downstream intergenic region that is in turn linked to the 5′ region of a downstream ORF has been conserved, and has served as the unit of gene evolution. The genes are tandem paralogous genes from the bacterium Staphylococcus aureus, for which more than ten entire genomes have been sequenced. We compared these multiple genome sequences at a locus for the lpl (lipoprotein-like) cluster (encoding lipoprotein homologs presumably related to their host interaction) in the genomic island termed νSaα. A highly conserved nucleotide sequence found within every lpl ORF is likely to provide a site for homologous recombination. Comparison of phylogenies of the 5′-variable region and the 3′-variable region within the same ORF revealed significant incongruence. In contrast, pairs of the 3′-variable region of an ORF and the 5′-variable region of the next downstream ORF gave more congruent phylogenies, with distinct groups of conserved pairs. The intergenic region seemed to have coevolved with the flanking variable regions. Multiple recombination events at the central conserved region appear to have caused various types of rearrangements among strains, shuffling the two variable regions in one ORF, but maintaining a conserved unit comprising the 3′-variable region, the intergenic region, and the 5′-variable region spanning adjacent ORFs. This result has strong impact on our understanding of gene evolution because most gene lineages underwent tandem duplication and then diversified. This work also illustrates the use of multiple genome sequences for high-resolution evolutionary analysis within the same species. PMID:18765438

  10. Multiple-contact discrete-element model for simulating dense granular media

    Science.gov (United States)

    Brodu, Nicolas; Dijksman, Joshua A.; Behringer, Robert P.

    2015-03-01

    This article presents a new force model for performing quantitative simulations of dense granular materials. Interactions between multiple contacts (MC) on the same grain are explicitly taken into account. Our readily applicable MC-DEM method retains all the advantages of discrete-element method simulations and does not require the use of costly finite-element methods. The new model closely reproduces our recent experimental measurements, including contact force distributions in full 3D, at all compression levels of the packing up to the experimental maximum limit of 13%. Comparisons with classic simulations using the nondeformable spheres approach, as well as with alternative models for interactions between multiple contacts, are provided. The success of our model, compared to these alternatives, demonstrates that interactions between multiple contacts on each grain must be included for dense granular packings.

  11. Dependence of Xmax and multiplicity of electron and muon on different high energy interaction models

    Directory of Open Access Journals (Sweden)

    G Rastegarzadeh

    2010-06-01

    Full Text Available Different high energy interaction models are the applied in CORSIKA code to simulate Extensive Air Showers (EAS generated by Cosmic Rays (CR. In this work the effects of QGSJET01, QGSJETII, DPMJET, SIBYLL models on Xmax and multiplicity of secondary electrons and muons at observation level are studied.

  12. Featuring Multiple Local Optima to Assist the User in the Interpretation of Induced Bayesian Network Models

    DEFF Research Database (Denmark)

    Dalgaard, Jens; Pena, Jose; Kocka, Tomas

    2004-01-01

    We propose a method to assist the user in the interpretation of the best Bayesian network model indu- ced from data. The method consists in extracting relevant features from the model (e.g. edges, directed paths and Markov blankets) and, then, assessing the con¯dence in them by studying multiple...

  13. Cognitive Models: The Missing Link to Learning Fraction Multiplication and Division

    Science.gov (United States)

    de Castro, Belinda V.

    2008-01-01

    This quasi-experimental study aims to streamline cognitive models on fraction multiplication and division that contain the most worthwhile features of other existing models. Its exploratory nature and its approach to proof elicitation can be used to help establish its effectiveness in building students' understanding of fractions as compared to…

  14. Non-invasive measurement of brain damage in a primate model of multiple sclerosis

    NARCIS (Netherlands)

    T Hart, B.A.; Vogels, J.; Bauer, J.; Brok, H.P.M.; Blezer, E.

    2004-01-01

    Early recognition of whether a product has potential as a new therapy for treating multiple sclerosis (MS) relies upon the quality of the animal models used in the preclinical trials. The promising effects of new treatments in rodent models of experimental autoimmune encephalomyelitis (EAE) have rar

  15. A Multivariate Model for the Meta-Analysis of Study Level Survival Data at Multiple Times

    Science.gov (United States)

    Jackson, Dan; Rollins, Katie; Coughlin, Patrick

    2014-01-01

    Motivated by our meta-analytic dataset involving survival rates after treatment for critical leg ischemia, we develop and apply a new multivariate model for the meta-analysis of study level survival data at multiple times. Our data set involves 50 studies that provide mortality rates at up to seven time points, which we model simultaneously, and…

  16. Modelling and simulation of multiple single - phase induction motor in parallel connection

    Directory of Open Access Journals (Sweden)

    Sujitjorn, S.

    2006-11-01

    Full Text Available A mathematical model for parallel connected n-multiple single-phase induction motors in generalized state-space form is proposed in this paper. The motor group draws electric power from one inverter. The model is developed by the dq-frame theory and was tested against four loading scenarios in which satisfactory results were obtained.

  17. A PROBABILISTIC INVENTORY MODEL FOR CONDITIONAL CREDIT PERIOD AND LEAD TIME WITH MULTIPLE STORAGE FACILITIES

    Directory of Open Access Journals (Sweden)

    S. S. Mishra

    2008-01-01

    Full Text Available A probabilistic inventory model for conditional credit period with exponential demand, non-zero lead time and multiple storage facility has been developed. The behaviour of total expected cost (TEC has been examined and the use and application of the model is demonstrated with the help of a numerical example.

  18. The Multiple Menu Model: A Successful Marriage for Integrating Content and Process.

    Science.gov (United States)

    Renzulli, Joseph S.

    1997-01-01

    The Multiple Menu Model is a practical set of planning guides that teachers can use to design indepth curriculum units. This model differs from traditional approaches by balancing content and process, involving students as inquirers, and exploring knowledge's structure and interconnectedness. Components include menus for knowledge, instructional…

  19. Supporting Students in Learning with Multiple Representation to Improve Student Mental Models on Atomic Structure Concepts

    Science.gov (United States)

    Sunyono; Yuanita, L.; Ibrahim, M.

    2015-01-01

    The aim of this research is identify the effectiveness of a multiple representation-based learning model, which builds a mental model within the concept of atomic structure. The research sample of 108 students in 3 classes is obtained randomly from among students of Mathematics and Science Education Studies using a stratified random sampling…

  20. Conceptual Incoherence as a Result of the Use of Multiple Historical Models in School Textbooks

    Science.gov (United States)

    Gericke, Niklas M.; Hagberg, Mariana

    2010-01-01

    This paper explores the occurrence of conceptual incoherence in upper secondary school textbooks resulting from the use of multiple historical models. Swedish biology and chemistry textbooks, as well as a selection of books from English speaking countries, were examined. The purpose of the study was to identify which models are used to represent…

  1. Pursuing the method of multiple working hypotheses to understand differences in process-based snow models

    Science.gov (United States)

    Clark, Martyn; Essery, Richard

    2017-04-01

    When faced with the complex and interdisciplinary challenge of building process-based land models, different modelers make different decisions at different points in the model development process. These modeling decisions are generally based on several considerations, including fidelity (e.g., what approaches faithfully simulate observed processes), complexity (e.g., which processes should be represented explicitly), practicality (e.g., what is the computational cost of the model simulations; are there sufficient resources to implement the desired modeling concepts), and data availability (e.g., is there sufficient data to force and evaluate models). Consequently the research community, comprising modelers of diverse background, experience, and modeling philosophy, has amassed a wide range of models, which differ in almost every aspect of their conceptualization and implementation. Model comparison studies have been undertaken to explore model differences, but have not been able to meaningfully attribute inter-model differences in predictive ability to individual model components because there are often too many structural and implementation differences among the different models considered. As a consequence, model comparison studies to date have provided limited insight into the causes of differences in model behavior, and model development has often relied on the inspiration and experience of individual modelers rather than on a systematic analysis of model shortcomings. This presentation will summarize the use of "multiple-hypothesis" modeling frameworks to understand differences in process-based snow models. Multiple-hypothesis frameworks define a master modeling template, and include a a wide variety of process parameterizations and spatial configurations that are used in existing models. Such frameworks provide the capability to decompose complex models into the individual decisions that are made as part of model development, and evaluate each decision in

  2. Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase.

    Directory of Open Access Journals (Sweden)

    Marcus J Tindall

    2010-08-01

    Full Text Available Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs and response regulators (RRs. These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1 the main RR controlling flagellar rotation, CheY(6, aided by its specific phosphatase, the bifunctional kinase CheA(3, acts as a phosphate sink for the other RRs; and (2 a phosphorelay pathway involving CheB(2 connects the cytoplasmic cluster kinase CheA(3 with the polar localised kinase CheA(2, and allows CheA(3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA(3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources.

  3. Genome-Scale Model Reveals Metabolic Basis of Biomass Partitioning in a Model Diatom.

    Directory of Open Access Journals (Sweden)

    Jennifer Levering

    Full Text Available Diatoms are eukaryotic microalgae that contain genes from various sources, including bacteria and the secondary endosymbiotic host. Due to this unique combination of genes, diatoms are taxonomically and functionally distinct from other algae and vascular plants and confer novel metabolic capabilities. Based on the genome annotation, we performed a genome-scale metabolic network reconstruction for the marine diatom Phaeodactylum tricornutum. Due to their endosymbiotic origin, diatoms possess a complex chloroplast structure which complicates the prediction of subcellular protein localization. Based on previous work we implemented a pipeline that exploits a series of bioinformatics tools to predict protein localization. The manually curated reconstructed metabolic network iLB1027_lipid accounts for 1,027 genes associated with 4,456 reactions and 2,172 metabolites distributed across six compartments. To constrain the genome-scale model, we determined the organism specific biomass composition in terms of lipids, carbohydrates, and proteins using Fourier transform infrared spectrometry. Our simulations indicate the presence of a yet unknown glutamine-ornithine shunt that could be used to transfer reducing equivalents generated by photosynthesis to the mitochondria. The model reflects the known biochemical composition of P. tricornutum in defined culture conditions and enables metabolic engineering strategies to improve the use of P. tricornutum for biotechnological applications.

  4. Genome-Scale Model Reveals Metabolic Basis of Biomass Partitioning in a Model Diatom.

    Science.gov (United States)

    Levering, Jennifer; Broddrick, Jared; Dupont, Christopher L; Peers, Graham; Beeri, Karen; Mayers, Joshua; Gallina, Alessandra A; Allen, Andrew E; Palsson, Bernhard O; Zengler, Karsten

    2016-01-01

    Diatoms are eukaryotic microalgae that contain genes from various sources, including bacteria and the secondary endosymbiotic host. Due to this unique combination of genes, diatoms are taxonomically and functionally distinct from other algae and vascular plants and confer novel metabolic capabilities. Based on the genome annotation, we performed a genome-scale metabolic network reconstruction for the marine diatom Phaeodactylum tricornutum. Due to their endosymbiotic origin, diatoms possess a complex chloroplast structure which complicates the prediction of subcellular protein localization. Based on previous work we implemented a pipeline that exploits a series of bioinformatics tools to predict protein localization. The manually curated reconstructed metabolic network iLB1027_lipid accounts for 1,027 genes associated with 4,456 reactions and 2,172 metabolites distributed across six compartments. To constrain the genome-scale model, we determined the organism specific biomass composition in terms of lipids, carbohydrates, and proteins using Fourier transform infrared spectrometry. Our simulations indicate the presence of a yet unknown glutamine-ornithine shunt that could be used to transfer reducing equivalents generated by photosynthesis to the mitochondria. The model reflects the known biochemical composition of P. tricornutum in defined culture conditions and enables metabolic engineering strategies to improve the use of P. tricornutum for biotechnological applications.

  5. A P-value model for theoretical power analysis and its applications in multiple testing procedures

    Directory of Open Access Journals (Sweden)

    Fengqing Zhang

    2016-10-01

    Full Text Available Abstract Background Power analysis is a critical aspect of the design of experiments to detect an effect of a given size. When multiple hypotheses are tested simultaneously, multiplicity adjustments to p-values should be taken into account in power analysis. There are a limited number of studies on power analysis in multiple testing procedures. For some methods, the theoretical analysis is difficult and extensive numerical simulations are often needed, while other methods oversimplify the information under the alternative hypothesis. To this end, this paper aims to develop a new statistical model for power analysis in multiple testing procedures. Methods We propose a step-function-based p-value model under the alternative hypothesis, which is simple enough to perform power analysis without simulations, but not too simple to lose the information from the alternative hypothesis. The first step is to transform distributions of different test statistics (e.g., t, chi-square or F to distributions of corresponding p-values. We then use a step function to approximate each of the p-value’s distributions by matching the mean and variance. Lastly, the step-function-based p-value model can be used for theoretical power analysis. Results The proposed model is applied to problems in multiple testing procedures. We first show how the most powerful critical constants can be chosen using the step-function-based p-value model. Our model is then applied to the field of multiple testing procedures to explain the assumption of monotonicity of the critical constants. Lastly, we apply our model to a behavioral weight loss and maintenance study to select the optimal critical constants. Conclusions The proposed model is easy to implement and preserves the information from the alternative hypothesis.

  6. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.

    Science.gov (United States)

    Xue, Jia; Schmidt, Susanne V; Sander, Jil; Draffehn, Astrid; Krebs, Wolfgang; Quester, Inga; De Nardo, Dominic; Gohel, Trupti D; Emde, Martina; Schmidleithner, Lisa; Ganesan, Hariharasudan; Nino-Castro, Andrea; Mallmann, Michael R; Labzin, Larisa; Theis, Heidi; Kraut, Michael; Beyer, Marc; Latz, Eicke; Freeman, Tom C; Ulas, Thomas; Schultze, Joachim L

    2014-02-20

    Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.

  7. An interval number-based multiple attribute bid-decision making model for substation equipments

    Directory of Open Access Journals (Sweden)

    Zhu Lili

    2016-01-01

    Full Text Available By analyzing the characteristics of public bidding for substation equipments and combining with the research methods of multiple attribute decision-making problems, a multiple attribute bid-decision making model is presented. Firstly, the weight of interval numbers is specified by using the interval numbers theory and entropy theory. Secondly, the deviation degree of decision-making scheme is proposed. Then the schemes are sorted. A typical case is analyzed based on the above-mentioned.

  8. Modeling and Decentralized Control for the Multiple UAVs Formation based on Lyapunov design and redesign

    OpenAIRE

    Hou, Zhicheng; Fantoni, Isabelle; Zavala-Río, Arturo

    2013-01-01

    International audience; This paper concerns the leader-follower multiple agent formation with nonlinear and coupled individual dynamics. We address the problem of multi-agent formation control by proposing a decentralized control strategy. The agents in the formation are quad-rotors UAVs. By attributing the high-order nonlinear and unmodelled dynamics as uncertainties, we propose a switching singular system model to represent the formation of the multiple UAVs system with switching topology. ...

  9. An Asymptotic Solvable Multiple "Look-Ahead" Model with Multi-weight

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A type of multiple "look-ahead" car-following models is studied by nonlinear analysis. The mKdV equation to describe density wave of traffic jamming is derived. The result indicates that the behavior of multiple "look-ahead" is in favor of stability enhancement of traffic flow. Furthermore, the traffic flow can reach the most stable case via adjustment of the parameter of weight functions m = 3.

  10. An Asymptotic Solvable Multiple ``Look-Ahead" Model with Multi-weight

    Science.gov (United States)

    Shi, Wei; Chen, Ning-Guo; Xue, Yu

    2007-12-01

    A type of multiple ``look-ahead" car-following models is studied by nonlinear analysis. The mKdV equation to describe density wave of traffic jamming is derived. The result indicates that the behavior of multiple ``look-ahead" is in favor of stability enhancement of traffic flow. Furthermore, the traffic flow can reach the most stable case via adjustment of the parameter of weight functions m = 3.

  11. DUAL RANDOM MODEL OF INCREASING LIFE INSURANCE FOR MULTIPLE-LIFE STATUS

    Institute of Scientific and Technical Information of China (English)

    ZhangYi; HeWenjiong

    2002-01-01

    In this paper the dual random model of increasing life insurance for multiple-life status is discussed. The rnth moment of the present value of benefits are calculated and the respective expressions of the moments under joint life status or last- survivor status are presented.Fur-thermore,the limiting distribution of average cost of a portfolio of increasing life insurance for multiple-life status is studied.

  12. Modeling of multivariate longitudinal phenotypes in family genetic studies with Bayesian multiplicity adjustment

    OpenAIRE

    Ding, Lili; Kurowski, Brad G; He, Hua; Alexander, Eileen S.; Mersha, Tesfaye B.; Fardo, David W.; Zhang, Xue; Pilipenko, Valentina V; Kottyan, Leah; Martin, Lisa J.

    2014-01-01

    Genetic studies often collect data on multiple traits. Most genetic association analyses, however, consider traits separately and ignore potential correlation among traits, partially because of difficulties in statistical modeling of multivariate outcomes. When multiple traits are measured in a pedigree longitudinally, additional challenges arise because in addition to correlation between traits, a trait is often correlated with its own measures over time and with measurements of other family...

  13. Multiplicity fluctuation and correlation of identified baryons in a quark combination model

    Science.gov (United States)

    Song, Jun; Li, Hai-hong; Wang, Rui-qin; Shao, Feng-lan

    2017-01-01

    The dynamical multiplicity fluctuations and correlations of identified baryons and antibaryons produced by the hadronization of a bulk quark system are systematically studied in a quark combination model. Starting from the most basic dynamics of the quark combination which is necessary for multiplicity study, we analyze moments (variance, skewness, and kurtosis) of inclusive multiplicity distributions of identified baryons, two-baryon multiplicity correlations, and baryon-antibaryon multiplicity correlations after the hadronization of a quark system with given quark number and antiquark number. We obtain a series of interesting results, e.g., binomial behavior of multiplicity moments, coinciding flavor-dependent two-baryon correlation, and universal baryon-antibaryon correlation, which can be regarded as general features of the quark combination. We further take into account correlations and fluctuations of quark numbers before hadronization and study their influence on multiple production of baryons and antibaryons. We find that quark number fluctuations and flavor conservation lead to a series of important results such as the negative p Ω¯ + multiplicity correlation and universal two-baryon correlations. We also study the influence of resonance decays in order to compare our results with future experimental data in ultrarelativistic heavy ion collisions at the Large Hadron Collider.

  14. Tumorigenic fragments of APC cause dominant defects in directional cell migration in multiple model systems

    Directory of Open Access Journals (Sweden)

    Scott A. Nelson

    2012-11-01

    Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APCMin/+; multiple intestinal neoplasia model demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+ intestines are overpopulated with cells, suggesting that a lack of migration might cause cell

  15. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis.

    Science.gov (United States)

    Bando, Yoshio; Nomura, Taichi; Bochimoto, Hiroki; Murakami, Koichi; Tanaka, Tatsuhide; Watanabe, Tsuyoshi; Yoshida, Shigetaka

    2015-02-01

    Demyelination and axonal damage are responsible for neurological deficits in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. However, the pathology of axonal damage in MS is not fully understood. In this study, histological analysis of morphological changes of axonal organelles during demyelination in murine models was investigated by scanning electron microscopy (SEM) using an osmium-maceration method. In cuprizone-induced demyelination, SEM showed typical morphology of demyelination in the corpus callosum of mouse brain. In contrast, SEM displayed variations in ultrastructural abnormalities of myelin structures and axonal organelles in spinal cord white matter of experimental autoimmune encephalomyelitis (EAE) mice, an animal model of MS. Myelin detachment and excessive myelin formation were observed as typical morphological myelin abnormalities in EAE. In addition, well-developed axoplasmic reticulum-like structures and accumulated mitochondria were observed in tortuous degenerating/degenerated axons and the length of mitochondria in axons of EAE spinal cord was shorter compared with naïve spinal cord. Immunohistochemistry also revealed dysfunction of mitochondrial fusion/fission machinery in EAE spinal cord axons. Moreover, the number of Y-shaped mitochondria was significantly increased in axons of the EAE spinal cord. Axonal morphologies in myelin basic protein-deficient shiverer mice were similar to those in EAE. However, shiverer mice had "tortuous" (S-curve shaped mitochondria) and larger mitochondria compared with wild-type and EAE mice. Lastly, analysis of human MS patient autopsied brains also demonstrated abnormal myelin structures in demyelinating lesions. These results indicate that morphological abnormalities of myelin and axonal organelles play important role on the pathogenesis of axonal injury in demyelinating diseases.

  16. A modeling and numerical algorithm for thermoporomechanics in multiple porosity media for naturally fractured reservoirs

    Science.gov (United States)

    Kim, J.; Sonnenthal, E. L.; Rutqvist, J.

    2011-12-01

    Rigorous modeling of coupling between fluid, heat, and geomechanics (thermo-poro-mechanics), in fractured porous media is one of the important and difficult topics in geothermal reservoir simulation, because the physics are highly nonlinear and strongly coupled. Coupled fluid/heat flow and geomechanics are investigated using the multiple interacting continua (MINC) method as applied to naturally fractured media. In this study, we generalize constitutive relations for the isothermal elastic dual porosity model proposed by Berryman (2002) to those for the non-isothermal elastic/elastoplastic multiple porosity model, and derive the coupling coefficients of coupled fluid/heat flow and geomechanics and constraints of the coefficients. When the off-diagonal terms of the total compressibility matrix for the flow problem are zero, the upscaled drained bulk modulus for geomechanics becomes the harmonic average of drained bulk moduli of the multiple continua. In this case, the drained elastic/elastoplastic moduli for mechanics are determined by a combination of the drained moduli and volume fractions in multiple porosity materials. We also determine a relation between local strains of all multiple porosity materials in a gridblock and the global strain of the gridblock, from which we can track local and global elastic/plastic variables. For elastoplasticity, the return mapping is performed for all multiple porosity materials in the gridblock. For numerical implementation, we employ and extend the fixed-stress sequential method of the single porosity model to coupled fluid/heat flow and geomechanics in multiple porosity systems, because it provides numerical stability and high accuracy. This sequential scheme can be easily implemented by using a porosity function and its corresponding porosity correction, making use of the existing robust flow and geomechanics simulators. We implemented the proposed modeling and numerical algorithm to the reaction transport simulator

  17. Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages.

    Science.gov (United States)

    Hilty, Markus; Wüthrich, Daniel; Salter, Susannah J; Engel, Hansjürg; Campbell, Samuel; Sá-Leão, Raquel; de Lencastre, Hermínia; Hermans, Peter; Sadowy, Ewa; Turner, Paul; Chewapreecha, Claire; Diggle, Mathew; Pluschke, Gerd; McGee, Lesley; Köseoğlu Eser, Özgen; Low, Donald E; Smith-Vaughan, Heidi; Endimiani, Andrea; Küffer, Marianne; Dupasquier, Mélanie; Beaudoing, Emmanuel; Weber, Johann; Bruggmann, Rémy; Hanage, William P; Parkhill, Julian; Hathaway, Lucy J; Mühlemann, Kathrin; Bentley, Stephen D

    2014-12-04

    The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent.

  18. Multiple soil nutrient competition between plants, microbes, and mineral surfaces: model development, parameterization, and example applications in several tropical forests

    Directory of Open Access Journals (Sweden)

    Q. Zhu

    2015-03-01

    Full Text Available Soil is a complex system where biotic (e.g., plant roots, micro-organisms and abiotic (e.g., mineral surfaces consumers compete for resources necessary for life (e.g., nitrogen, phosphorus. This competition is ecologically significant, since it regulates the dynamics of soil nutrients and controls aboveground plant productivity. Here we develop, calibrate, and test a nutrient competition model that accounts for multiple soil nutrients interacting with multiple biotic and abiotic consumers. As applied here for tropical forests, the Nutrient COMpetition model (N-COM includes three primary soil nutrients (NH4+, NO3−, and POx (representing the sum of PO43−, HPO42−, and H2PO4− and five potential competitors (plant roots, decomposing microbes, nitrifiers, denitrifiers, and mineral surfaces. The competition is formulated with a quasi-steady-state chemical equilibrium approximation to account for substrate (multiple substrates share one consumer and consumer (multiple consumers compete for one substrate effects. N-COM successfully reproduced observed soil heterotrophic respiration, N2O emissions, free phosphorus, sorbed phosphorus, and free NH4+ at a tropical forest site (Tapajos. The overall model posterior uncertainty was moderately well constrained. Our sensitivity analysis revealed that soil nutrient competition was primarily regulated by consumer-substrate affinity rather than environmental factors such as soil temperature or soil moisture. Our results imply that the competitiveness (from most to least competitive followed this order: (1 for NH4+, nitrifiers ~ decomposing microbes > plant roots, (2 for NO3−, denitrifiers ~ decomposing microbes > plant roots, (3 for POx, mineral surfaces > decomposing microbes ~ plant roots. Although smaller, plant relative competitiveness is of the same order of magnitude as microbes. We then applied the N-COM model to analyze field nitrogen and phosphorus perturbation experiments in two tropical forest

  19. Multiple soil nutrient competition between plants, microbes, and mineral surfaces: model development, parameterization, and example applications in several tropical forests

    Science.gov (United States)

    Zhu, Q.; Riley, W. J.; Tang, J.; Koven, C. D.

    2016-01-01

    Soil is a complex system where biotic (e.g., plant roots, micro-organisms) and abiotic (e.g., mineral surfaces) consumers compete for resources necessary for life (e.g., nitrogen, phosphorus). This competition is ecologically significant, since it regulates the dynamics of soil nutrients and controls aboveground plant productivity. Here we develop, calibrate and test a nutrient competition model that accounts for multiple soil nutrients interacting with multiple biotic and abiotic consumers. As applied here for tropical forests, the Nutrient COMpetition model (N-COM) includes three primary soil nutrients (NH4+, NO3- and POx; representing the sum of PO43-, HPO42- and H2PO4-) and five potential competitors (plant roots, decomposing microbes, nitrifiers, denitrifiers and mineral surfaces). The competition is formulated with a quasi-steady-state chemical equilibrium approximation to account for substrate (multiple substrates share one consumer) and consumer (multiple consumers compete for one substrate) effects. N-COM successfully reproduced observed soil heterotrophic respiration, N2O emissions, free phosphorus, sorbed phosphorus and NH4+ pools at a tropical forest site (Tapajos). The overall model uncertainty was moderately well constrained. Our sensitivity analysis revealed that soil nutrient competition was primarily regulated by consumer-substrate affinity rather than environmental factors such as soil temperature or soil moisture. Our results also imply that under strong nutrient limitation, relative competitiveness depends strongly on the competitor functional traits (affinity and nutrient carrier enzyme abundance). We then applied the N-COM model to analyze field nitrogen and phosphorus perturbation experiments in two tropical forest sites (in Hawaii and Puerto Rico) not used in model development or calibration. Under soil inorganic nitrogen and phosphorus elevated conditions, the model accurately replicated the experimentally observed competition among

  20. Proximate analysis based multiple regression models for higher heating value estimation of low rank coals

    Energy Technology Data Exchange (ETDEWEB)

    Akkaya, Ali Volkan [Department of Mechanical Engineering, Yildiz Technical University, 34349 Besiktas, Istanbul (Turkey)

    2009-02-15

    In this paper, multiple nonlinear regression models for estimation of higher heating value of coals are developed using proximate analysis data obtained generally from the low rank coal samples as-received basis. In this modeling study, three main model structures depended on the number of proximate analysis parameters, which are named the independent variables, such as moisture, ash, volatile matter and fixed carbon, are firstly categorized. Secondly, sub-model structures with different arrangements of the independent variables are considered. Each sub-model structure is analyzed with a number of model equations in order to find the best fitting model using multiple nonlinear regression method. Based on the results of nonlinear regression analysis, the best model for each sub-structure is determined. Among them, the models giving highest correlation for three main structures are selected. Although the selected all three models predicts HHV rather accurately, the model involving four independent variables provides the most accurate estimation of HHV. Additionally, when the chosen model with four independent variables and a literature model are tested with extra proximate analysis data, it is seen that that the developed model in this study can give more accurate prediction of HHV of coals. It can be concluded that the developed model is effective tool for HHV estimation of low rank coals. (author)