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Sample records for genetic constraints guide

  1. Constraints in Genetic Programming

    NASA Technical Reports Server (NTRS)

    Janikow, Cezary Z.

    1996-01-01

    Genetic programming refers to a class of genetic algorithms utilizing generic representation in the form of program trees. For a particular application, one needs to provide the set of functions, whose compositions determine the space of program structures being evolved, and the set of terminals, which determine the space of specific instances of those programs. The algorithm searches the space for the best program for a given problem, applying evolutionary mechanisms borrowed from nature. Genetic algorithms have shown great capabilities in approximately solving optimization problems which could not be approximated or solved with other methods. Genetic programming extends their capabilities to deal with a broader variety of problems. However, it also extends the size of the search space, which often becomes too large to be effectively searched even by evolutionary methods. Therefore, our objective is to utilize problem constraints, if such can be identified, to restrict this space. In this publication, we propose a generic constraint specification language, powerful enough for a broad class of problem constraints. This language has two elements -- one reduces only the number of program instances, the other reduces both the space of program structures as well as their instances. With this language, we define the minimal set of complete constraints, and a set of operators guaranteeing offspring validity from valid parents. We also show that these operators are not less efficient than the standard genetic programming operators if one preprocesses the constraints - the necessary mechanisms are identified.

  2. Genetic map construction with constraints

    SciTech Connect

    Clark, D.A.; Rawlings, C.J.; Soursenot, S.

    1994-12-31

    A pilot program, CME, is described for generating a physical genetic map from hybridization fingerprinting data. CME is implemented in the parallel constraint logic programming language ElipSys. The features of constraint logic programming are used to enable the integration of preexisting mapping information (partial probe orders from cytogenetic maps and local physical maps) into the global map generation process, while parallelism enables the search space to be traversed more efficiently. CME was tested using data from chromosome 2 of Schizosaccharomyces pombe and was found able to generate maps as well as (and sometimes better than) a more traditional method. This paper illustrates the practical benefits of using a symbolic logic programming language and shows that the features of constraint handling and parallel execution bring the development of practical systems based on Al programming technologies nearer to being a reality.

  3. Genetic Constraints on Protein Evolution

    PubMed Central

    Camps, Manel; Herman, Asael; Loh, Ern; Loeb, Lawrence A.

    2013-01-01

    Evolution requires the generation and optimization of new traits (“adaptation”) and involves the selection of mutations that improve cellular function. These mutations were assumed to arise by selection of neutral mutations present at all times in the population. Here we review recent evidence that indicates that deleterious mutations are more frequent in the population than previously recognized and these mutations play a significant role in protein evolution through continuous positive selection. Positively selected mutations include adaptive mutations, i.e. mutations that directly affect enzymatic function, and compensatory mutations, which suppress the pleiotropic effects of adaptive mutations. Compensatory mutations are by far the most frequent of the two and would allow potentially adaptive but deleterious mutations to persist long enough in the population to be positively selected during episodes of adaptation. Compensatory mutations are, by definition, context-dependent and thus constrain the paths available for evolution. This provides a mechanistic basis for the examples of highly constrained evolutionary landscapes and parallel evolution reported in natural and experimental populations. The present review article describes these recent advances in the field of protein evolution and discusses their implications for understanding the genetic basis of disease and for protein engineering in vitro. PMID:17917869

  4. Genetic constraints on protein evolution.

    PubMed

    Camps, Manel; Herman, Asael; Loh, Ern; Loeb, Lawrence A

    2007-01-01

    Evolution requires the generation and optimization of new traits ("adaptation") and involves the selection of mutations that improve cellular function. These mutations were assumed to arise by selection of neutral mutations present at all times in the population. Here we review recent evidence that indicates that deleterious mutations are more frequent in the population than previously recognized and that these mutations play a significant role in protein evolution through continuous positive selection. Positively selected mutations include adaptive mutations, i.e. mutations that directly affect enzymatic function, and compensatory mutations, which suppress the pleiotropic effects of adaptive mutations. Compensatory mutations are by far the most frequent of the two and would allow potentially adaptive but deleterious mutations to persist long enough in the population to be positively selected during episodes of adaptation. Compensatory mutations are, by definition, context-dependent and thus constrain the paths available for evolution. This provides a mechanistic basis for the examples of highly constrained evolutionary landscapes and parallel evolution reported in natural and experimental populations. The present review article describes these recent advances in the field of protein evolution and discusses their implications for understanding the genetic basis of disease and for protein engineering in vitro.

  5. Lagrangian and Hamiltonian constraints for guiding-center Hamiltonian theories

    SciTech Connect

    Tronko, Natalia; Brizard, Alain J.

    2015-11-15

    A consistent guiding-center Hamiltonian theory is derived by Lie-transform perturbation method, with terms up to second order in magnetic-field nonuniformity. Consistency is demonstrated by showing that the guiding-center transformation presented here satisfies separate Jacobian and Lagrangian constraints that have not been explored before. A new first-order term appearing in the guiding-center phase-space Lagrangian is identified through a calculation of the guiding-center polarization. It is shown that this new polarization term also yields a simpler expression of the guiding-center toroidal canonical momentum, which satisfies an exact conservation law in axisymmetric magnetic geometries. Finally, an application of the guiding-center Lagrangian constraint on the guiding-center Hamiltonian yields a natural interpretation for its higher-order corrections.

  6. Active constraint control for image-guided robotic surgery.

    PubMed

    Yen, P-L; Davies, B L

    2010-01-01

    The concept of active constraint control for image-guided robotic surgery is introduced, together with its benefits and a short outline of its history. The clinical use of active constraint control in orthopaedic surgery is discussed, together with the outcomes of a clinical trial for unicondylar knee replacement surgery. The evolution of the robotic design from large costly structures towards simpler, more cost-effective systems is also presented, leading to the design of the Acrobot 'Sculptor' system. A new approach to the achievement of robotic total knee replacement is also presented, in which a high-speed rotary cutter is used to slice through the bone to achieve a speedy resection. The control concept is presented, together with the results of trials on animal bones and a cadaver, showing that it is possible to remove large quantities of bone both quickly and accurately.

  7. The contribution of selection and genetic constraints to phenotypic divergence.

    PubMed

    Chenoweth, Stephen F; Rundle, Howard D; Blows, Mark W

    2010-02-01

    Although divergent natural selection is common in nature, the extent to which genetic constraints bias evolutionary trajectories in its presence remains largely unknown. Here we develop a general framework to integrate estimates of divergent selection and genetic constraints to estimate their contributions to phenotypic divergence among natural populations. We apply these methods to estimates of phenotypic selection and genetic covariance from sexually selected traits that have undergone adaptive divergence among nine natural populations of the fly Drosophila serrata. Despite ongoing sexual selection within populations, differences in its direction among them, and genetic variance for all traits in all populations, divergent sexual selection only weakly resembled the observed pattern of divergence. Accounting for the influence of genetic covariance among the traits significantly improved the alignment between observed and predicted divergence. Our results suggest that the direction in which sexual selection generates divergence may depend on the pattern of genetic constraint in individual populations, ultimately restricting how sexually selected traits may diversify. More generally, we show how evolution is likely to proceed in the direction of major axes of genetic variance, rather than the direction of selection itself, when genetic variance-covariance matrices are ill conditioned and genetic variance is low in the direction of selection.

  8. Environmental Constraints Guide Migration of Malaria Parasites during Transmission

    PubMed Central

    Hellmann, Janina Kristin; Münter, Sylvia; Kudryashev, Mikhail; Schulz, Simon; Heiss, Kirsten; Müller, Ann-Kristin; Matuschewski, Kai; Spatz, Joachim P.; Schwarz, Ulrich S.; Frischknecht, Friedrich

    2011-01-01

    Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. In order to systematically examine how sporozoite migration depends on the structure of the environment, we studied it in micro-fabricated obstacle arrays. The trajectories observed in vivo and in vitro closely resemble each other suggesting that structural constraints can be sufficient to guide Plasmodium sporozoites in complex environments. Sporozoite speed in different environments is optimized for migration and correlates with persistence length and dispersal. However, this correlation breaks down in mutant sporozoites that show adhesion impairment due to the lack of TRAP-like protein (TLP) on their surfaces. This may explain their delay in infecting the host. The flexibility of sporozoite adaption to different environments and a favorable speed for optimal dispersal ensures efficient host switching during malaria transmission. PMID:21698220

  9. Genetic effects on infant handedness under spatial constraint conditions.

    PubMed

    Suzuki, Kunitake; Ando, Juko; Satou, Naho

    2009-12-01

    Previous studies have reported a genetic influence on the individual differences in adult handedness; however, relatively little is known about genetic influences on the development of infant hand selection. In the current study, we examined whether genetic influences on handedness are expressed in various spatial locations in infants aged 18 months using the twin method. Infants were asked to respond to targets positioned in left, middle, and right locations using grasping movements. Results showed that similarities in hand selection within monozygotic twin pairs was more than two times higher than that of the dizygotic twin pairs in the middle location. In the left location, similarities in hand selection within monozygotic and dizygotic twin pairs were low. In addition, low individual differences in hand selection in the right location were also observed. These results suggest a non-additive genetic influence on handedness, and that spatial constraint is a crucial factor for the expression of genetic effects on handedness in infants.

  10. Constraints on the Genetic and Antigenic Variability of Measles Virus

    PubMed Central

    Beaty, Shannon M.; Lee, Benhur

    2016-01-01

    Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation. PMID:27110809

  11. Constraints on the Genetic and Antigenic Variability of Measles Virus.

    PubMed

    Beaty, Shannon M; Lee, Benhur

    2016-04-21

    Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.

  12. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-04-07

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

  13. Using activity-based costing and theory of constraints to guide continuous improvement in managed care.

    PubMed

    Roybal, H; Baxendale, S J; Gupta, M

    1999-01-01

    Activity-based costing and the theory of constraints have been applied successfully in many manufacturing organizations. Recently, those concepts have been applied in service organizations. This article describes the application of activity-based costing and the theory of constraints in a managed care mental health and substance abuse organization. One of the unique aspects of this particular application was the integration of activity-based costing and the theory of constraints to guide process improvement efforts. This article describes the activity-based costing model and the application of the theory of constraint's focusing steps with an emphasis on unused capacities of activities in the organization.

  14. Genetic constraints on adaptive evolution in principle and in practice

    NASA Astrophysics Data System (ADS)

    Weinreich, Daniel

    2014-03-01

    Geneticists have long recognized that pairs of mutations often produce surprising effects on the organism, given their effects in isolation. Such mutational interactions are called epistasis. Importantly, epistasis among mutations influencing an organism's survival or reproductive success can constrain the temporal order in which mutations will be favored by natural selection. After exploring these theoretical considerations more fully, we will demonstrate substantial epistatic constraint on the evolution of an enzyme that confers bacterial antibiotic resistance. Such epistatically induced constraints turn out to be rather common in enzyme evolution, and we will briefly discuss recent work that seeks to explicate its mechanistic basis using methods of molecular and structural biology. Finally we observe that the epistatic interaction between two mutations itself often varies with genetic context, implying the existence of higher-order interactions. We present a computational framework for assessing magnitude of epistatic interactions of all orders, and show that non-negligible epistatic interactions of all orders are common in a diverse set of biological systems. Work supported by NIGMS Award R01GM095728 and NSF Emerging Frontiers Award 1038657

  15. Genetic programming over context-free languages with linear constraints for the knapsack problem: first results.

    PubMed

    Bruhn, Peter; Geyer-Schulz, Andreas

    2002-01-01

    In this paper, we introduce genetic programming over context-free languages with linear constraints for combinatorial optimization, apply this method to several variants of the multidimensional knapsack problem, and discuss its performance relative to Michalewicz's genetic algorithm with penalty functions. With respect to Michalewicz's approach, we demonstrate that genetic programming over context-free languages with linear constraints improves convergence. A final result is that genetic programming over context-free languages with linear constraints is ideally suited to modeling complementarities between items in a knapsack problem: The more complementarities in the problem, the stronger the performance in comparison to its competitors.

  16. 75 FR 36445 - Draft Regulatory Guide, DG-4018, “Constraint on Releases of Airborne Radioactive Materials To the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

    ... COMMISSION Draft Regulatory Guide, DG-4018, ``Constraint on Releases of Airborne Radioactive Materials To the... of Airborne Radioactive Materials to the Environment for Licensees Other than Power Reactors.'' This....resource@nrc.gov . The Draft Regulatory Guide, DG-4018, ``Constraint on Releases of Airborne Radioactive...

  17. A guide to the genetics of psychiatric disease.

    PubMed

    Hough, Christopher J; Ursano, Robert J

    2006-01-01

    The road to scientific discovery begins with an awareness of what is unknown. Research in science can in some ways be like putting together the pieces of a puzzle without having the benefit of the box-top picture of the completed puzzle. The "picture" in science is an understanding of how nature works in a particular instance, and it takes many separate pieces of the "puzzle" to put this understanding together. These pieces are always of different kinds of data, often obtained using different approaches and techniques. The challenge of the researcher is to picture or hypothesize each of the missing pieces before actually having them in hand, so they can be sought and tested in the laboratory. This "picturing" is actually having a clear idea of what you don't know: having a clear image of the "shape" of the missing piece. This is easy when the puzzle surrounding the missing piece is already in hand, but more difficult with less of it constrained by what is already known. In putting paper puzzles together, the shape of the pieces is not the only limitation that needs to be satisfied. There is also the picture to satisfy, that is, the picture usually has to make sense. In science these constraints can be manifold, and usually the quality of the research is judged by the number of ways a piece of data integrates into and brings together the rest of the puzzle. The multidimensionality of scientific questions makes it virtually essential that as many different pieces of the puzzle as possible be obtained. The more that is not known about the puzzle, the more pieces you need. Thus it is with the genetics of psychiatric diseases. In this guide, we will explore as many of the domains of the genetic puzzle as we are aware of. We will learn a bit of the language of each and how they fit into the puzzle with at least one anecdote to serve as an example. Mapping unknown territory is always a process, but we hope this guide will increase the reader's awareness of what is unknown.

  18. Genetics and behavior: a guide for practitioners.

    PubMed

    Overall, Karen L; Tiira, Katriina; Broach, Desiree; Bryant, Deborah

    2014-05-01

    Phenotyping behavior is difficult, partly because behavior is almost always influenced by environment. Using objective terms/criteria to evaluate behaviors is best; the more objective the assessment, the more likely underlying genetic patterns will be identified. Behavioral pathologies, and highly desirable behavioral characteristics/traits, are likely complex, meaning that multiple genes are probably involved, and therefore simple genetic tests are less possible. Breeds can be improved using traditional quantitative genetic methods; unfortunately, this also creates the possibility of inadvertently selecting for covarying undesirable behaviors. Patterns of behaviors within families and breed lines are still the best guidelines for genetic counseling in dogs.

  19. Social constraints, genetic vulnerability, and mental health following collective stress.

    PubMed

    Holman, E Alison; Lucas-Thompson, Rachel G; Lu, Tammy

    2011-10-01

    A repeat-length polymorphism of the serotonin promoter gene (5-HTTLPR) has been associated with depression and posttraumatic stress disorder (PTSD) in trauma-exposed individuals reporting unsupportive social environments. We examine the contributions of the triallelic 5-HTTLPR genotype and social constraints to posttraumatic stress (PTS) symptoms in a national sample following the September 11, 2001 (9/11) terrorist attacks. Saliva was collected by mail from 711 respondents (European American subsample n = 463) of a large national probability sample of 2,729 adults. Respondents completed web-based assessments of pre-9/11 mental and physical health, acute stress 9 to 23 days post-9/11, PTS symptoms, and social constraints on disclosure regarding fears of future terrorist attacks 2-3 years post-9/11. Social constraints were positively associated with PTS symptoms 2-3 years post-9/11. The triallelic 5-HTTLPR genotype was not directly associated with PTS symptoms, but it interacted with social constraints to predict PTS symptoms 2-3 years post-9/11: Social constraints were more strongly associated with PTS symptoms for individuals with any s/lg allele than for homozygous la/la individuals. Constraints on disclosing fears about future terrorism moderate the 5-HTTLPR genotype-PTS symptom association even when indirectly exposed to collective stress. Copyright © 2011 International Society for Traumatic Stress Studies.

  20. How much can the orientation of G's eigenvectors tell us about genetic constraints?

    PubMed Central

    Berner, Daniel

    2012-01-01

    A key goal in evolutionary quantitative genetics is to understand how evolutionary trajectories are constrained by pleiotropic coupling among multiple traits. Because studying pleiotropic constraints directly at the molecular genetic level remains very difficult, several analytical approaches attempt to draw conclusions about constraints by relating the orientation of the eigenvectors of the traits' (co)variance matrix to vectors of multivariate selection. On the basis of explicit models of genetic architecture, I here argue that the value of such approaches is greatly overestimated. The reason is that eigenvector orientation can be highly unstable and lack a biologically meaningful relationship with the underlying traits' genetic architecture. Genetic constraints are more profitably explored through experimental approaches avoiding the mathematical abstraction inherent in eigenanalysis. PMID:22957186

  1. A guided search genetic algorithm using mined rules for optimal affective product design

    NASA Astrophysics Data System (ADS)

    Fung, Chris K. Y.; Kwong, C. K.; Chan, Kit Yan; Jiang, H.

    2014-08-01

    Affective design is an important aspect of new product development, especially for consumer products, to achieve a competitive edge in the marketplace. It can help companies to develop new products that can better satisfy the emotional needs of customers. However, product designers usually encounter difficulties in determining the optimal settings of the design attributes for affective design. In this article, a novel guided search genetic algorithm (GA) approach is proposed to determine the optimal design attribute settings for affective design. The optimization model formulated based on the proposed approach applied constraints and guided search operators, which were formulated based on mined rules, to guide the GA search and to achieve desirable solutions. A case study on the affective design of mobile phones was conducted to illustrate the proposed approach and validate its effectiveness. Validation tests were conducted, and the results show that the guided search GA approach outperforms the GA approach without the guided search strategy in terms of GA convergence and computational time. In addition, the guided search optimization model is capable of improving GA to generate good solutions for affective design.

  2. BiC2PAM: constraint-guided biclustering for biological data analysis with domain knowledge.

    PubMed

    Henriques, Rui; Madeira, Sara C

    2016-01-01

    Biclustering has been largely used in biological data analysis, enabling the discovery of putative functional modules from omic and network data. Despite the recognized importance of incorporating domain knowledge to guide biclustering and guarantee a focus on relevant and non-trivial biclusters, this possibility has not yet been comprehensively addressed. This results from the fact that the majority of existing algorithms are only able to deliver sub-optimal solutions with restrictive assumptions on the structure, coherency and quality of biclustering solutions, thus preventing the up-front satisfaction of knowledge-driven constraints. Interestingly, in recent years, a clearer understanding of the synergies between pattern mining and biclustering gave rise to a new class of algorithms, termed as pattern-based biclustering algorithms. These algorithms, able to efficiently discover flexible biclustering solutions with optimality guarantees, are thus positioned as good candidates for knowledge incorporation. In this context, this work aims to bridge the current lack of solid views on the use of background knowledge to guide (pattern-based) biclustering tasks. This work extends (pattern-based) biclustering algorithms to guarantee the satisfiability of constraints derived from background knowledge and to effectively explore efficiency gains from their incorporation. In this context, we first show the relevance of constraints with succinct, (anti-)monotone and convertible properties for the analysis of expression data and biological networks. We further show how pattern-based biclustering algorithms can be adapted to effectively prune of the search space in the presence of such constraints, as well as be guided in the presence of biological annotations. Relying on these contributions, we propose BiClustering with Constraints using PAttern Mining (BiC2PAM), an extension of BicPAM and BicNET biclustering algorithms. Experimental results on biological data demonstrate the

  3. Convergence Rate of the Successive Zooming Genetic Algorithm for Band-Widths of Equality Constraint

    NASA Astrophysics Data System (ADS)

    Kwon, Y. D.; Han, S. W.; Do, J. W.

    Modern optimization techniques, such as the steepest descent method, Newton's method, Rosen's gradient projection method, genetic algorithms, etc., have been developed and quickly improved with the progress of digital computers. The steepest descent method and Newton's method are applied efficiently to unconstrained problems. For many engineering problems involving constraints, the genetic algorithm and SUMT1are applied with relative ease. Genetic algorithms2have global search characteristics and relatively good convergence rates. Recently, a Successive Zooming Genetic Algorithm (SZGA)3,4 was introduced that can search the precise optimal solution at any level of desired accuracy. In the case of engineering problems involving an equality constraint, even if good optimization techniques are applied to the constraint problems, a proper constraint range can lead to a more rapid convergence and precise solution. This study investigated the proper band-width of an equality constraint using the Successive Zooming Genetic Algorithm (SZGA) technique both theoretically and numerically. We were able to find a certain band-width range of the rapid convergence for each problem, and a broad but more general one too.

  4. Constraint genetic algorithm and its application in sintering proportioning

    NASA Astrophysics Data System (ADS)

    Wu, Tiebin; Liu, Yunlian; Tang, Wenyan; Li, Xinjun; Yu, Yi

    2017-09-01

    This paper puts forward a method for constrained optimization problems based on self-adaptive penalty function and improved genetic algorithm. In order to improve the speed of convergence and avoid premature convergence, a method based on good-point set theory has been proposed. By using good point set method for generating initial population, the initial population is uniformly distributed in the solution space. This paper Designs an elite reverse learning strategy, and proposes a mechanism to automatically adjust the crossover probability according to the individual advantages and disadvantages. The tests indicate that the proposed constrained genetic algorithm is efficient and feasible.

  5. Deformable Image Registration with Local Rigidity Constraints for Cone-Beam CT Guided Spine Surgery

    PubMed Central

    Reaungamornrat, S.; Wang, A. S.; Uneri, A.; Otake, Y.; Khanna, A. J.; Siewerdsen, J. H.

    2014-01-01

    Image-guided spine surgery is associated with reduced co-morbidity and improved surgical outcome. However, precise localization of target anatomy and adjacent nerves and vessels relative to planning information (e.g., device trajectories) can be challenged by anatomical deformation. Rigid registration alone fails to account for deformation associated with changes in spine curvature, and conventional deformable registration fails to account for rigidity of the vertebrae, causing unrealistic distortions in the registered image that can confound high-precision surgery. We developed and evaluated a deformable registration method capable of preserving rigidity of bones while resolving the deformation of surrounding soft tissue. The method aligns preoperative CT to intraoperative CBCT using free-form deformation (FFD) with constraints on rigid body motion imposed according to a simple intensity threshold of bone intensities. The constraints enforced 3 properties of a rigid transformation – namely, constraints on affinity (AC), orthogonality (OC), and properness (PC). The method also incorporated an injectivity constraint (IC) to preserve topology. Physical experiments involving phantoms, an ovine spine, and a human cadaver as well as digital simulations were performed to evaluate the sensitivity to registration parameters, preservation of rigid body morphology, and overall registration accuracy of constrained FFD in comparison to conventional unconstrained FFD (denoted uFFD) and Demons registration. FFD with orthogonality and injectivity constraints (denoted FFD+OC+IC) demonstrated improved performance compared to uFFD and Demons. Affinity and properness constraints offered little or no additional improvement. The FFD+OC+IC method preserved rigid body morphology at near-ideal values of zero dilatation (𝒟 = 0.05, compared to 0.39 and 0.56 for uFFD and Demons, respectively) and shear (𝒮 = 0.08, compared to 0.36 and 0.44 for uFFD and Demons, respectively

  6. Guiding rational reservoir flood operation using penalty-type genetic algorithm

    NASA Astrophysics Data System (ADS)

    Chang, Li-Chiu

    2008-06-01

    SummaryReal-time flood control of a multi-purpose reservoir should consider decreasing the flood peak stage downstream and storing floodwaters for future usage during typhoon seasons. This study proposes a reservoir flood control optimization model with linguistic description of requirements and existing regulations for rational operating decisions. The approach involves formulating reservoir flood operation as an optimization problem and using the genetic algorithm (GA) as a search engine. The optimizing formulation is expressed not only by mathematical forms of objective function and constraints, but also by no analytic expression in terms of parameters. GA is used to search a global optimum of a mixture of mathematical and nonmathematical formulations. Due to the great number of constraints and flood control requirements, it is difficult to reach a solution without violating constraints. To tackle this bottleneck, the proper penalty strategy for each parameter is proposed to guide the GA searching process. The proposed approach is applied to the Shihmen reservoir in North Taiwan for finding the rational release and desired storage as a case study. The hourly historical data sets of 29 typhoon events that have hit the area in last thirty years are investigated bye the proposed method. To demonstrate the effectiveness of the proposed approach, the simplex method was performed. The results demonstrated that a penalty-type genetic algorithm could effectively provide rational hydrographs to reduce flood damage during the flood operation and to increase final storage for future usages.

  7. Genetic constraints for thermal coadaptation in Drosophila subobscura

    PubMed Central

    2010-01-01

    Background Behaviour has been traditionally viewed as a driver of subsequent evolution because behavioural adjustments expose organisms to novel environments, which may result in a correlated evolution on other traits. In Drosophila subobscura, thermal preference and heat tolerance are linked to chromosomal inversion polymorphisms that show parallel latitudinal clines worldwide, such that "cold-climate" ("warm-climate") chromosome arrangements collectively favour a coherent response to colder (warmer) settings as flies carrying them prefer colder (warmer) conditions and have lower (higher) knock out temperatures. Yet, it is not clear whether a genetic correlation between thermal preference and heat tolerance can partially underlie such response. Results We have analyzed the genetic basis of thermal preference and heat tolerance using isochromosomal lines in D. subobscura. Chromosome arrangements on the O chromosome were known to have a biometrical effect on thermal preference in a laboratory temperature gradient, and also harbour several genes involved in the heat shock response; in particular, the genes Hsp68 and Hsp70. Our results corroborate that arrangements on chromosome O affect adult thermal preference in a laboratory temperature gradient, with cold-climate Ost carriers displaying a lower thermal preference than their warm-climate O3+4 and O3+4+8 counterparts. However, these chromosome arrangements did not have any effect on adult heat tolerance and, hence, we putatively discard a genetic covariance between both traits arising from linkage disequilibrium between genes affecting thermal preference and candidate genes for heat shock resistance. Nonetheless, a possible association of juvenile thermal preference and heat resistance warrants further analysis. Conclusions Thermal preference and heat tolerance in the isochromosomal lines of D. subobscura appear to be genetically independent, which might potentially prevent a coherent response of behaviour and

  8. Genetic determinants and cellular constraints in noisy gene expression

    PubMed Central

    Sanchez, Alvaro; Golding, Ido

    2014-01-01

    In individual cells, transcription is a random process obeying single-molecule kinetics. Often, it occurs in a bursty, intermittent manner. The frequency and size of these bursts affect the magnitude of temporal fluctuations in mRNA and protein content within a cell, creating variation or “noise” in gene expression. It is still unclear to what degree transcriptional kinetics are specific to each gene and determined by its promoter sequence. Alternative scenarios have been proposed, where the kinetics of transcription are governed by cellular constraints and follow universal rules across the genome. Evidence from genome-wide noise studies and from systematic perturbations of promoter sequences suggest that both scenarios—namely gene-specific versus genome-wide regulation of transcription kinetics— may be present to different degrees in bacteria, yeast and animal cells. PMID:24311680

  9. Genetic constraints and the evolution of display trait sexual dimorphism by natural and sexual selection.

    PubMed

    Chenoweth, Stephen F; Rundle, Howard D; Blows, Mark W

    2008-01-01

    The evolution of sexual dimorphism involves an interaction between sex-specific selection and a breakdown of genetic constraints that arise because the two sexes share a genome. We examined genetic constraints and the effect of sex-specific selection on a suite of sexually dimorphic display traits in Drosophila serrata. Sexual dimorphism varied among nine natural populations covering a substantial portion of the species range. Quantitative genetic analyses showed that intersexual genetic correlations were high because of autosomal genetic variance but that the inclusion of X-linked effects reduced genetic correlations substantially, indicating that sex linkage may be an important mechanism by which intersexual genetic constraints are reduced in this species. We then explored the potential for both natural and sexual selection to influence these traits, using a 12-generation laboratory experiment in which we altered the opportunities for each process as flies adapted to a novel environment. Sexual dimorphism evolved, with natural selection reducing sexual dimorphism, whereas sexual selection tended to increase it overall. To this extent, our results are consistent with the hypothesis that sexual selection favors evolutionary divergence of the sexes. However, sex-specific responses to natural and sexual selection contrasted with the classic model because sexual selection affected females rather than males.

  10. Genetic analysis of life-history constraint and evolution in a wild ungulate population.

    PubMed

    Morrissey, Michael B; Walling, Craig A; Wilson, Alastair J; Pemberton, Josephine M; Clutton-Brock, Tim H; Kruuk, Loeske E B

    2012-04-01

    Trade-offs among life-history traits are central to evolutionary theory. In quantitative genetic terms, trade-offs may be manifested as negative genetic covariances relative to the direction of selection on phenotypic traits. Although the expression and selection of ecologically important phenotypic variation are fundamentally multivariate phenomena, the in situ quantification of genetic covariances is challenging. Even for life-history traits, where well-developed theory exists with which to relate phenotypic variation to fitness variation, little evidence exists from in situ studies that negative genetic covariances are an important aspect of the genetic architecture of life-history traits. In fact, the majority of reported estimates of genetic covariances among life-history traits are positive. Here we apply theory of the genetics and selection of life histories in organisms with complex life cycles to provide a framework for quantifying the contribution of multivariate genetically based relationships among traits to evolutionary constraint. We use a Bayesian framework to link pedigree-based inference of the genetic basis of variation in life-history traits to evolutionary demography theory regarding how life histories are selected. Our results suggest that genetic covariances may be acting to constrain the evolution of female life-history traits in a wild population of red deer Cervus elaphus: genetic covariances are estimated to reduce the rate of adaptation by about 40%, relative to predicted evolutionary change in the absence of genetic covariances. Furthermore, multivariate phenotypic (rather than genetic) relationships among female life-history traits do not reveal this constraint.

  11. Deformable image registration with local rigidity constraints for cone-beam CT-guided spine surgery

    NASA Astrophysics Data System (ADS)

    Reaungamornrat, S.; Wang, A. S.; Uneri, A.; Otake, Y.; Khanna, A. J.; Siewerdsen, J. H.

    2014-07-01

    Image-guided spine surgery (IGSS) is associated with reduced co-morbidity and improved surgical outcome. However, precise localization of target anatomy and adjacent nerves and vessels relative to planning information (e.g., device trajectories) can be challenged by anatomical deformation. Rigid registration alone fails to account for deformation associated with changes in spine curvature, and conventional deformable registration fails to account for rigidity of the vertebrae, causing unrealistic distortions in the registered image that can confound high-precision surgery. We developed and evaluated a deformable registration method capable of preserving rigidity of bones while resolving the deformation of surrounding soft tissue. The method aligns preoperative CT to intraoperative cone-beam CT (CBCT) using free-form deformation (FFD) with constraints on rigid body motion imposed according to a simple intensity threshold of bone intensities. The constraints enforced three properties of a rigid transformation—namely, constraints on affinity (AC), orthogonality (OC), and properness (PC). The method also incorporated an injectivity constraint (IC) to preserve topology. Physical experiments involving phantoms, an ovine spine, and a human cadaver as well as digital simulations were performed to evaluate the sensitivity to registration parameters, preservation of rigid body morphology, and overall registration accuracy of constrained FFD in comparison to conventional unconstrained FFD (uFFD) and Demons registration. FFD with orthogonality and injectivity constraints (denoted FFD+OC+IC) demonstrated improved performance compared to uFFD and Demons. Affinity and properness constraints offered little or no additional improvement. The FFD+OC+IC method preserved rigid body morphology at near-ideal values of zero dilatation ({ D} = 0.05, compared to 0.39 and 0.56 for uFFD and Demons, respectively) and shear ({ S} = 0.08, compared to 0.36 and 0.44 for uFFD and Demons

  12. A family genetic risk communication framework: guiding tool development in genetics health services.

    PubMed

    Wiens, Miriam E; Wilson, Brenda J; Honeywell, Christina; Etchegary, Holly

    2013-04-01

    Family communication of genetic risk information is a complex process. Currently, there are no evidence-based interventions to help genetics professionals facilitate the process of disclosure within families. This study was designed to create a framework to assist in the development of tools to support patients in communicating genetic risk information to family members. A systematic review identified the factors relevant in communicating genetic risk information in families. A guiding theory for the proposed framework was selected and populated with the factors identified from the review. The review identified 112 factors of relevance. The theory of planned behaviour was selected to guide framework development, organising the framework in terms of the patient's attitudes about disclosure, perceived pressure to disclose and perceived control over disclosure. Attitudes about disclosure are influenced by a desire to protect oneself or family members, and the patient's perceptions of relevance of the information for family members, responsibility to disclose, family members' rights to information and the usefulness of communicating. Perceived pressure to disclose information is shaped by genetic professionals, family members and society. Perceived control over disclosure is affected by family relationships/dynamics, personal communication skills, the ability of the patient and family to understand the information and coping skills of the patient and family member. The family genetic risk communication framework presents a concise synthesis of the evidence on family communication of genetic information; it may be useful in creating and evaluating tools to help genetic counsellors and patients with communication issues.

  13. The evolution of developmental patterning under genetic duplication constraints.

    PubMed

    Fuentes, Miguel A; Krakauer, David C

    2008-02-06

    Of considerable interest are the evolutionary and developmental origins of complex, adaptive structures and the mechanisms that stabilize these structures. We consider the relationship between the evolutionary process of gene duplication and deletion and the stability of morphogenetic patterns produced by interacting activators and inhibitors. We compare the relative stability of patterns with a single activator and inhibitor (two-dimensional system) against a 'redundant' system with two activators or two inhibitors (three-dimensional system). We find that duplication events can both expand and contract the space of patterns. We study developmental robustness in terms of stochastic escape times from this space, also known as a 'canalization potential'. We embed the output of pattern formation into an explicit evolutionary model of gene duplication, gene loss and variation in the steepness of the canalization potential. We find that under all constant conditions, the system evolves towards a preference for steep potentials associated with low phenotypic variability and longer lifespans. This preference leads to an overall decrease in the density of redundant genotypes as developmental robustness neutralizes the advantages of genetic robustness.

  14. Technical guide for genetic advancement of underdeveloped and intractable Clostridium.

    PubMed

    Pyne, Michael E; Bruder, Mark; Moo-Young, Murray; Chung, Duane A; Chou, C Perry

    2014-01-01

    In recent years, the genus Clostridium has risen to the forefront of both medical biotechnology and industrial biotechnology owing to its potential in applications as diverse as anticancer therapy and production of commodity chemicals and biofuels. The prevalence of hyper-virulent strains of C. difficile within medical institutions has also led to a global epidemic that demands a more thorough understanding of clostridial genetics, physiology, and pathogenicity. Unfortunately, Clostridium suffers from a lack of sophisticated genetic tools and techniques which has hindered the biotechnological exploitation of this important bacterial genus. This review provides a comprehensive summary of biotechnological progress made in clostridial genetic tool development, while also aiming to serve as a technical guide for the advancement of underdeveloped clostridial strains, including recalcitrant species, novel environmental samples, and non-type strains. Relevant strain engineering techniques, from genome sequencing and establishment of a gene transfer methodology through to deployment of advanced genome editing procedures, are discussed in detail to provide a blueprint for future clostridial strain construction endeavors. It is expected that a more thorough and rounded-out genetic toolkit available for use in the clostridia will bring about the construction of superior bioprocessing strains and a more complete understanding of clostridial genetics, physiology, and pathogenicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Statistical estimates of fundamental constraints on the use of commercial CCD cameras in TV guide systems of large optical telescopes

    NASA Astrophysics Data System (ADS)

    Komarov, V. V.; Fomenko, A. F.

    2007-03-01

    The parameters of TV guide cameras of the BTA and Zeiss-1000 telescopes are analyzed. The formation of optical images by the “atmosphere + telescope” system is analyzed with allowance for the laws of photoelectron statistics in order to justify the applicability of commercial CCD cameras in the guiding systems of large optical telescopes. The analysis focuses on the estimates of fundamental constraints imposed on the method of TV observations of the sky through a turbulent atmosphere. The possible ways of reducing the main constraining factors in the case of the use of highly sensitive commercially produced CCDs in TV guide cameras are outlined.

  16. Genetic Code Evolution Reveals the Neutral Emergence of Mutational Robustness, and Information as an Evolutionary Constraint

    PubMed Central

    Massey, Steven E.

    2015-01-01

    The standard genetic code (SGC) is central to molecular biology and its origin and evolution is a fundamental problem in evolutionary biology, the elucidation of which promises to reveal much about the origins of life. In addition, we propose that study of its origin can also reveal some fundamental and generalizable insights into mechanisms of molecular evolution, utilizing concepts from complexity theory. The first is that beneficial traits may arise by non-adaptive processes, via a process of “neutral emergence”. The structure of the SGC is optimized for the property of error minimization, which reduces the deleterious impact of point mutations. Via simulation, it can be shown that genetic codes with error minimization superior to the SGC can emerge in a neutral fashion simply by a process of genetic code expansion via tRNA and aminoacyl-tRNA synthetase duplication, whereby similar amino acids are added to codons related to that of the parent amino acid. This process of neutral emergence has implications beyond that of the genetic code, as it suggests that not all beneficial traits have arisen by the direct action of natural selection; we term these “pseudaptations”, and discuss a range of potential examples. Secondly, consideration of genetic code deviations (codon reassignments) reveals that these are mostly associated with a reduction in proteome size. This code malleability implies the existence of a proteomic constraint on the genetic code, proportional to the size of the proteome (P), and that its reduction in size leads to an “unfreezing” of the codon – amino acid mapping that defines the genetic code, consistent with Crick’s Frozen Accident theory. The concept of a proteomic constraint may be extended to propose a general informational constraint on genetic fidelity, which may be used to explain variously, differences in mutation rates in genomes with differing proteome sizes, differences in DNA repair capacity and genome GC content

  17. Genetic code evolution reveals the neutral emergence of mutational robustness, and information as an evolutionary constraint.

    PubMed

    Massey, Steven E

    2015-04-24

    The standard genetic code (SGC) is central to molecular biology and its origin and evolution is a fundamental problem in evolutionary biology, the elucidation of which promises to reveal much about the origins of life. In addition, we propose that study of its origin can also reveal some fundamental and generalizable insights into mechanisms of molecular evolution, utilizing concepts from complexity theory. The first is that beneficial traits may arise by non-adaptive processes, via a process of "neutral emergence". The structure of the SGC is optimized for the property of error minimization, which reduces the deleterious impact of point mutations. Via simulation, it can be shown that genetic codes with error minimization superior to the SGC can emerge in a neutral fashion simply by a process of genetic code expansion via tRNA and aminoacyl-tRNA synthetase duplication, whereby similar amino acids are added to codons related to that of the parent amino acid. This process of neutral emergence has implications beyond that of the genetic code, as it suggests that not all beneficial traits have arisen by the direct action of natural selection; we term these "pseudaptations", and discuss a range of potential examples. Secondly, consideration of genetic code deviations (codon reassignments) reveals that these are mostly associated with a reduction in proteome size. This code malleability implies the existence of a proteomic constraint on the genetic code, proportional to the size of the proteome (P), and that its reduction in size leads to an "unfreezing" of the codon - amino acid mapping that defines the genetic code, consistent with Crick's Frozen Accident theory. The concept of a proteomic constraint may be extended to propose a general informational constraint on genetic fidelity, which may be used to explain variously, differences in mutation rates in genomes with differing proteome sizes, differences in DNA repair capacity and genome GC content between organisms, a

  18. Patterns of genetic variation and covariation in ejaculate traits reveal potential evolutionary constraints in guppies.

    PubMed

    Evans, J P

    2011-05-01

    Ejaculates comprise multiple and potentially interacting traits that determine male fertility and sperm competitiveness. Consequently, selection on these traits is likely to be intense, but the efficacy of selection will depend critically on patterns of genetic variation and covariation underlying their expression. In this study, I provide a prospective quantitative genetic analysis of ejaculate traits in the guppy Poecilia reticulata, a highly promiscuous live-bearing fish. I used a standard paternal half-sibling breeding design to characterize patterns of genetic (co)variation in components of sperm length and in vitro sperm performance. All traits exhibited high levels of phenotypic and additive genetic variation, and in several cases, patterns of genetic variation was consistent with Y-linkage. There were also highly significant negative genetic correlations between the various measures of sperm length and sperm performance. In particular, the length of the sperm's midpiece was strongly, negatively and genetically correlated with sperm's swimming velocity-an important determinant of sperm competitiveness in this and other species. Other components of sperm length, including the flagellum and head, were independently and negatively genetically correlated with the proportion of live sperm in the ejaculate (sperm viability). Whether these relationships represent evolutionary trade-offs depends on the precise relationships between these traits and competitive fertilization rates, which have yet to be fully resolved in this (and indeed most) species. Nevertheless, these prospective analyses point to potential constraints on ejaculate evolution and may explain the high level of phenotypic variability in ejaculate traits in this species.

  19. Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.

    PubMed

    Yan, Jingwen; Du, Lei; Kim, Sungeun; Risacher, Shannon L; Huang, Heng; Moore, Jason H; Saykin, Andrew J; Shen, Li

    2014-09-01

    Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate technique used in imaging genetics to identify complex multi-SNP-multi-QT associations. However, most of the existing SCCA algorithms are designed using the soft thresholding method, which assumes that the input features are independent from one another. This assumption clearly does not hold for the imaging genetic data. In this article, we propose a new knowledge-guided SCCA algorithm (KG-SCCA) to overcome this limitation as well as improve learning results by incorporating valuable prior knowledge. The proposed KG-SCCA method is able to model two types of prior knowledge: one as a group structure (e.g. linkage disequilibrium blocks among SNPs) and the other as a network structure (e.g. gene co-expression network among brain regions). The new model incorporates these prior structures by introducing new regularization terms to encourage weight similarity between grouped or connected features. A new algorithm is designed to solve the KG-SCCA model without imposing the independence constraint on the input features. We demonstrate the effectiveness of our algorithm with both synthetic and real data. For real data, using an Alzheimer's disease (AD) cohort, we examine the imaging genetic associations between all SNPs in the APOE gene (i.e. top AD gene) and amyloid deposition measures among cortical regions (i.e. a major AD hallmark). In comparison with a widely used SCCA implementation, our KG-SCCA algorithm produces not only improved cross-validation performances but also biologically meaningful

  20. Trait Associations across Evolutionary Time within a Drosophila Phylogeny: Correlated Selection or Genetic Constraint?

    PubMed Central

    Kellermann, Vanessa; Overgaard, Johannes; Loeschcke, Volker; Kristensen, Torsten Nygaard; Hoffmann, Ary A.

    2013-01-01

    Traits do not evolve independently. To understand how trait changes under selection might constrain adaptive changes, phenotypic and genetic correlations are typically considered within species, but these capture constraints across a few generations rather than evolutionary time. For longer-term constraints, comparisons are needed across species but associations may arise because of correlated selection pressures rather than genetic interactions. Implementing a unique approach, we use known patterns of selection to separate likely trait correlations arising due to correlated selection from those reflecting genetic constraints. We examined the evolution of stress resistance in >90 Drosophila species adapted to a range of environments, while controlling for phylogeny. Initially we examined the role of climate and phylogeny in shaping the evolution of starvation and body size, two traits previously not examined in this context. Following correction for phylogeny only a weak relationship between climate and starvation resistance was detected, while all of the variation in the relationship between body size and climate could be attributed to phylogeny. Species were divided into three environmental groups (hot and dry, hot and wet, cold) with the expectation that, if genetic correlations underpin trait correlations, these would persist irrespective of the environment, whereas selection-driven evolution should produce correlations dependent on the environment. We found positive associations between most traits in hot and dry environments coupled with high trait means. In contrast few trait correlations were observed in hot/wet and cold environments. These results suggest trait associations are primarily driven by correlated selection rather than genetic interactions, highlighting that such interactions are unlikely to limit evolution of stress resistance. PMID:24015206

  1. An Improved Hierarchical Genetic Algorithm for Sheet Cutting Scheduling with Process Constraints

    PubMed Central

    Rao, Yunqing; Qi, Dezhong; Li, Jinling

    2013-01-01

    For the first time, an improved hierarchical genetic algorithm for sheet cutting problem which involves n cutting patterns for m non-identical parallel machines with process constraints has been proposed in the integrated cutting stock model. The objective of the cutting scheduling problem is minimizing the weighted completed time. A mathematical model for this problem is presented, an improved hierarchical genetic algorithm (ant colony—hierarchical genetic algorithm) is developed for better solution, and a hierarchical coding method is used based on the characteristics of the problem. Furthermore, to speed up convergence rates and resolve local convergence issues, a kind of adaptive crossover probability and mutation probability is used in this algorithm. The computational result and comparison prove that the presented approach is quite effective for the considered problem. PMID:24489491

  2. Fast and Easy 3D Reconstruction with the Help of Geometric Constraints and Genetic Algorithms

    NASA Astrophysics Data System (ADS)

    Annich, Afafe; El Abderrahmani, Abdellatif; Satori, Khalid

    2017-09-01

    The purpose of the work presented in this paper is to describe new method of 3D reconstruction from one or more uncalibrated images. This method is based on two important concepts: geometric constraints and genetic algorithms (GAs). At first, we are going to discuss the combination between bundle adjustment and GAs that we have proposed in order to improve 3D reconstruction efficiency and success. We used GAs in order to improve fitness quality of initial values that are used in the optimization problem. It will increase surely convergence rate. Extracted geometric constraints are used first to obtain an estimated value of focal length that helps us in the initialization step. Matching homologous points and constraints is used to estimate the 3D model. In fact, our new method gives us a lot of advantages: reducing the estimated parameter number in optimization step, decreasing used image number, winning time and stabilizing good quality of 3D results. At the end, without any prior information about our 3D scene, we obtain an accurate calibration of the cameras, and a realistic 3D model that strictly respects the geometric constraints defined before in an easy way. Various data and examples will be used to highlight the efficiency and competitiveness of our present approach.

  3. Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

    PubMed

    Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

    2017-02-01

    Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA.

  4. Pharmacogenetics: Using Genetic Information to Guide Drug Therapy

    PubMed Central

    CHANG, KU-LANG; WEITZEL, KRISTIN; SCHMIDT, SIEGFRIED

    2016-01-01

    Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects. PMID:26447442

  5. Indirect genetics effects and evolutionary constraint: an analysis of social dominance in red deer, Cervus elaphus.

    PubMed

    Wilson, A J; Morrissey, M B; Adams, M J; Walling, C A; Guinness, F E; Pemberton, J M; Clutton-Brock, T H; Kruuk, L E B

    2011-04-01

    By determining access to limited resources, social dominance is often an important determinant of fitness. Thus, if heritable, standard theory predicts mean dominance should evolve. However, dominance is usually inferred from the tendency to win contests, and given one winner and one loser in any dyadic contest, the mean proportion won will always equal 0.5. Here, we argue that the apparent conflict between quantitative genetic theory and common sense is resolved by recognition of indirect genetic effects (IGEs). We estimate selection on, and genetic (co)variance structures for, social dominance, in a wild population of red deer Cervus elaphus, on the Scottish island of Rum. While dominance is heritable and positively correlated with lifetime fitness, contest outcomes depend as much on the genes carried by an opponent as on the genotype of a focal individual. We show how this dependency imposes an absolute evolutionary constraint on the phenotypic mean, thus reconciling theoretical predictions with common sense. More generally, we argue that IGEs likely provide a widespread but poorly recognized source of evolutionary constraint for traits influenced by competition.

  6. A restoration genetics guide for coral reef conservation.

    PubMed

    Baums, Iliana B

    2008-06-01

    Worldwide degradation of coral reef communities has prompted a surge in restoration efforts. They proceed largely without considering genetic factors because traditionally, coral populations have been regarded as open over large areas with little potential for local adaptation. Since, biophysical and molecular studies indicated that most populations are closed over shorter time and smaller spatial scales. Thus, it is justified to re-examine the potential for site adaptation in corals. There is ample evidence for differentiated populations, inbreeding, asexual reproduction and the occurrence of ecotypes, factors that may facilitate local adaptation. Discovery of widespread local adaptation would influence coral restoration projects mainly with regard to the physical and evolutionary distance from the source wild and/or captive bred propagules may be moved without causing a loss of fitness in the restored population. Proposed causes for loss of fitness as a result of (plant) restoration efforts include founder effects, genetic swamping, inbreeding and/or outbreeding depression. Direct evidence for any of these processes is scarce in reef corals due to a lack of model species that allow for testing over multiple generations and the separation of the relative contributions of algal symbionts and their coral hosts to the overall performance of the coral colony. This gap in our knowledge may be closed by employing novel population genetic and genomics approaches. The use of molecular tools may aid managers in the selection of appropriate propagule sources, guide spatial arrangement of transplants, and help in assessing the success of coral restoration projects by tracking the performance of transplants, thereby generating important data for future coral reef conservation and restoration projects.

  7. Little effect of seasonal constraints on population genetic structure in eusocial paper wasps.

    PubMed

    Lengronne, Thibault; Leadbeater, Ellouise; Patalano, Solenn; Dreier, Stephanie; Field, Jeremy; Sumner, Seirian; Keller, Laurent

    2012-10-01

    Climate has long been suggested to affect population genetic structures of eusocial insect societies. For instance, Hamilton [Journal of Theoretical Biology7 (1964) 17] discusses whether temperate and tropical eusocial insects may show differences in population-level genetic structure and viscosity, and how this might relate to differences in the degree of synchrony in their life cycles or modes of nest founding. Despite the importance of Hamilton's 1964 papers, this specific idea has not been tested in actual populations of wasps, probably due to the paucity of studies on tropical species. Here, we compare colony and population genetic structures in two species of primitively eusocial paper wasps with contrasting ecologies: the tropical species Polistes canadensis and the temperate species P. dominulus. Our results provide important clarifications of Hamilton's discussion. Specifically, we show that the genetic structures of the temperate and tropical species were very similar, indicating that seasonality does not greatly affect population viscosity or inbreeding. For both species, the high genetic differentiation between nests suggests strong selection at the nest level to live with relatives, whereas low population viscosity and low genetic differentiation between nest aggregations might reflect balancing selection to disperse, avoiding competition with relatives. Overall, our study suggests no prevalence of seasonal constraints of the life cycle in affecting the population genetic structure of eusocial paper wasps. These conclusions are likely to apply also to other primitively eusocial insects, such as halictine bees. They also highlight how selection for a kin structure that promotes altruism can override potential effects of ecology in eusocial insects.

  8. Little effect of seasonal constraints on population genetic structure in eusocial paper wasps

    PubMed Central

    Lengronne, Thibault; Leadbeater, Ellouise; Patalano, Solenn; Dreier, Stephanie; Field, Jeremy; Sumner, Seirian; Keller, Laurent

    2012-01-01

    Climate has long been suggested to affect population genetic structures of eusocial insect societies. For instance, Hamilton [Journal of Theoretical Biology 7 (1964) 17] discusses whether temperate and tropical eusocial insects may show differences in population-level genetic structure and viscosity, and how this might relate to differences in the degree of synchrony in their life cycles or modes of nest founding. Despite the importance of Hamilton's 1964 papers, this specific idea has not been tested in actual populations of wasps, probably due to the paucity of studies on tropical species. Here, we compare colony and population genetic structures in two species of primitively eusocial paper wasps with contrasting ecologies: the tropical species Polistes canadensis and the temperate species P. dominulus. Our results provide important clarifications of Hamilton's discussion. Specifically, we show that the genetic structures of the temperate and tropical species were very similar, indicating that seasonality does not greatly affect population viscosity or inbreeding. For both species, the high genetic differentiation between nests suggests strong selection at the nest level to live with relatives, whereas low population viscosity and low genetic differentiation between nest aggregations might reflect balancing selection to disperse, avoiding competition with relatives. Overall, our study suggests no prevalence of seasonal constraints of the life cycle in affecting the population genetic structure of eusocial paper wasps. These conclusions are likely to apply also to other primitively eusocial insects, such as halictine bees. They also highlight how selection for a kin structure that promotes altruism can override potential effects of ecology in eusocial insects. PMID:23145345

  9. Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants

    PubMed Central

    Bagley, Steven C.; Sirota, Marina; Chen, Richard; Butte, Atul J.; Altman, Russ B.

    2016-01-01

    Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups. PMID:27115429

  10. A multivariate analysis of genetic constraints to life history evolution in a wild population of red deer.

    PubMed

    Walling, Craig A; Morrissey, Michael B; Foerster, Katharina; Clutton-Brock, Tim H; Pemberton, Josephine M; Kruuk, Loeske E B

    2014-12-01

    Evolutionary theory predicts that genetic constraints should be widespread, but empirical support for their existence is surprisingly rare. Commonly applied univariate and bivariate approaches to detecting genetic constraints can underestimate their prevalence, with important aspects potentially tractable only within a multivariate framework. However, multivariate genetic analyses of data from natural populations are challenging because of modest sample sizes, incomplete pedigrees, and missing data. Here we present results from a study of a comprehensive set of life history traits (juvenile survival, age at first breeding, annual fecundity, and longevity) for both males and females in a wild, pedigreed, population of red deer (Cervus elaphus). We use factor analytic modeling of the genetic variance-covariance matrix ( G: ) to reduce the dimensionality of the problem and take a multivariate approach to estimating genetic constraints. We consider a range of metrics designed to assess the effect of G: on the deflection of a predicted response to selection away from the direction of fastest adaptation and on the evolvability of the traits. We found limited support for genetic constraint through genetic covariances between traits, both within sex and between sexes. We discuss these results with respect to other recent findings and to the problems of estimating these parameters for natural populations.

  11. A Multivariate Analysis of Genetic Constraints to Life History Evolution in a Wild Population of Red Deer

    PubMed Central

    Walling, Craig A.; Morrissey, Michael B.; Foerster, Katharina; Clutton-Brock, Tim H.; Pemberton, Josephine M.; Kruuk, Loeske E. B.

    2014-01-01

    Evolutionary theory predicts that genetic constraints should be widespread, but empirical support for their existence is surprisingly rare. Commonly applied univariate and bivariate approaches to detecting genetic constraints can underestimate their prevalence, with important aspects potentially tractable only within a multivariate framework. However, multivariate genetic analyses of data from natural populations are challenging because of modest sample sizes, incomplete pedigrees, and missing data. Here we present results from a study of a comprehensive set of life history traits (juvenile survival, age at first breeding, annual fecundity, and longevity) for both males and females in a wild, pedigreed, population of red deer (Cervus elaphus). We use factor analytic modeling of the genetic variance–covariance matrix (G) to reduce the dimensionality of the problem and take a multivariate approach to estimating genetic constraints. We consider a range of metrics designed to assess the effect of G on the deflection of a predicted response to selection away from the direction of fastest adaptation and on the evolvability of the traits. We found limited support for genetic constraint through genetic covariances between traits, both within sex and between sexes. We discuss these results with respect to other recent findings and to the problems of estimating these parameters for natural populations. PMID:25278555

  12. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints.

    PubMed

    Sessions, October M; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients' sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses.

  13. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints

    PubMed Central

    Sessions, October M.; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M.; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R.; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients’ sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses. PMID:26327586

  14. Unifying Genetic Canalization, Genetic Constraint, and Genotype-by-Environment Interaction: QTL by Genomic Background by Environment Interaction of Flowering Time in Boechera stricta

    PubMed Central

    Lee, Cheng-Ruei; Anderson, Jill T.; Mitchell-Olds, Thomas

    2014-01-01

    Natural populations exhibit substantial variation in quantitative traits. A quantitative trait is typically defined by its mean and variance, and to date most genetic mapping studies focus on loci altering trait means but not (co)variances. For single traits, the control of trait variance across genetic backgrounds is referred to as genetic canalization. With multiple traits, the genetic covariance among different traits in the same environment indicates the magnitude of potential genetic constraint, while genotype-by-environment interaction (GxE) concerns the same trait across different environments. While some have suggested that these three attributes of quantitative traits are different views of similar concepts, it is not yet clear, however, whether they have the same underlying genetic mechanism. Here, we detect quantitative trait loci (QTL) influencing the (co)variance of phenological traits in six distinct environments in Boechera stricta, a close relative of Arabidopsis. We identified nFT as the QTL altering the magnitude of phenological trait canalization, genetic constraint, and GxE. Both the magnitude and direction of nFT's canalization effects depend on the environment, and to our knowledge, this reversibility of canalization across environments has not been reported previously. nFT's effects on trait covariance structure (genetic constraint and GxE) likely result from the variable and reversible canalization effects across different traits and environments, which can be explained by the interaction among nFT, genomic backgrounds, and environmental stimuli. This view is supported by experiments demonstrating significant nFT by genomic background epistatic interactions affecting phenological traits and expression of the candidate gene, FT. In contrast to the well-known canalization gene Hsp90, the case of nFT may exemplify an alternative mechanism: Our results suggest that (at least in traits with major signal integrators such as flowering time) genetic

  15. Insight into the ten-penny problem: guiding search by constraints and maximization.

    PubMed

    Öllinger, Michael; Fedor, Anna; Brodt, Svenja; Szathmáry, Eörs

    2016-09-03

    For a long time, insight problem solving has been either understood as nothing special or as a particular class of problem solving. The first view implicates the necessity to find efficient heuristics that restrict the search space, the second, the necessity to overcome self-imposed constraints. Recently, promising hybrid cognitive models attempt to merge both approaches. In this vein, we were interested in the interplay of constraints and heuristic search, when problem solvers were asked to solve a difficult multi-step problem, the ten-penny problem. In three experimental groups and one control group (N = 4 × 30) we aimed at revealing, what constraints drive problem difficulty in this problem, and how relaxing constraints, and providing an efficient search criterion facilitates the solution. We also investigated how the search behavior of successful problem solvers and non-solvers differ. We found that relaxing constraints was necessary but not sufficient to solve the problem. Without efficient heuristics that facilitate the restriction of the search space, and testing the progress of the problem solving process, the relaxation of constraints was not effective. Relaxing constraints and applying the search criterion are both necessary to effectively increase solution rates. We also found that successful solvers showed promising moves earlier and had a higher maximization and variation rate across solution attempts. We propose that this finding sheds light on how different strategies contribute to solving difficult problems. Finally, we speculate about the implications of our findings for insight problem solving.

  16. Flexible Job-Shop Scheduling with Dual-Resource Constraints to Minimize Tardiness Using Genetic Algorithm

    NASA Astrophysics Data System (ADS)

    Paksi, A. B. N.; Ma'ruf, A.

    2016-02-01

    In general, both machines and human resources are needed for processing a job on production floor. However, most classical scheduling problems have ignored the possible constraint caused by availability of workers and have considered only machines as a limited resource. In addition, along with production technology development, routing flexibility appears as a consequence of high product variety and medium demand for each product. Routing flexibility is caused by capability of machines that offers more than one machining process. This paper presents a method to address scheduling problem constrained by both machines and workers, considering routing flexibility. Scheduling in a Dual-Resource Constrained shop is categorized as NP-hard problem that needs long computational time. Meta-heuristic approach, based on Genetic Algorithm, is used due to its practical implementation in industry. Developed Genetic Algorithm uses indirect chromosome representative and procedure to transform chromosome into Gantt chart. Genetic operators, namely selection, elitism, crossover, and mutation are developed to search the best fitness value until steady state condition is achieved. A case study in a manufacturing SME is used to minimize tardiness as objective function. The algorithm has shown 25.6% reduction of tardiness, equal to 43.5 hours.

  17. The ethics of characterizing difference: guiding principles on using racial categories in human genetics.

    PubMed

    Lee, Sandra Soo-Jin; Mountain, Joanna; Koenig, Barbara; Altman, Russ; Brown, Melissa; Camarillo, Albert; Cavalli-Sforza, Luca; Cho, Mildred; Eberhardt, Jennifer; Feldman, Marcus; Ford, Richard; Greely, Henry; King, Roy; Markus, Hazel; Satz, Debra; Snipp, Matthew; Steele, Claude; Underhill, Peter

    2008-01-01

    We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation.

  18. The ethics of characterizing difference: guiding principles on using racial categories in human genetics

    PubMed Central

    Lee, Sandra Soo-Jin; Mountain, Joanna; Koenig, Barbara; Altman, Russ; Brown, Melissa; Camarillo, Albert; Cavalli-Sforza, Luca; Cho, Mildred; Eberhardt, Jennifer; Feldman, Marcus; Ford, Richard; Greely, Henry; King, Roy; Markus, Hazel; Satz, Debra; Snipp, Matthew; Steele, Claude; Underhill, Peter

    2008-01-01

    We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation. PMID:18638359

  19. Geographic variation of melanisation patterns in a hornet species: genetic differences, climatic pressures or aposematic constraints?

    PubMed

    Perrard, Adrien; Arca, Mariangela; Rome, Quentin; Muller, Franck; Tan, Jiangli; Bista, Sanjaya; Nugroho, Hari; Baudoin, Raymond; Baylac, Michel; Silvain, Jean-François; Carpenter, James M; Villemant, Claire

    2014-01-01

    Coloration of stinging insects is often based on contrasted patterns of light and black pigmentations as a warning signal to predators. However, in many social wasp species, geographic variation drastically modifies this signal through melanic polymorphism potentially driven by different selective pressures. To date, surprisingly little is known about the geographic variation of coloration of social wasps in relation to aposematism and melanism and to genetic and developmental constraints. The main objectives of this study are to improve the description of the colour variation within a social wasp species and to determine which factors are driving this variation. Therefore, we explored the evolutionary history of a polymorphic hornet, Vespa velutina Lepeletier, 1836, using mitochondrial and microsatellite markers, and we analysed its melanic variation using a colour space based on a description of body parts coloration. We found two main lineages within the species and confirmed the previous synonymy of V. auraria Smith, 1852, under V. velutina, differing only by the coloration. We also found that the melanic variation of most body parts was positively correlated, with some segments forming potential colour modules. Finally, we showed that the variation of coloration between populations was not related to their molecular, geographic or climatic differences. Our observations suggest that the coloration patterns of hornets and their geographic variations are determined by genes with an influence of developmental constraints. Our results also highlight that Vespa velutina populations have experienced several convergent evolutions of the coloration, more likely influenced by constraints on aposematism and Müllerian mimicry than by abiotic pressures on melanism.

  20. Geographic Variation of Melanisation Patterns in a Hornet Species: Genetic Differences, Climatic Pressures or Aposematic Constraints?

    PubMed Central

    Perrard, Adrien; Arca, Mariangela; Rome, Quentin; Muller, Franck; Tan, Jiangli; Bista, Sanjaya; Nugroho, Hari; Baudoin, Raymond; Baylac, Michel; Silvain, Jean-François; Carpenter, James M.; Villemant, Claire

    2014-01-01

    Coloration of stinging insects is often based on contrasted patterns of light and black pigmentations as a warning signal to predators. However, in many social wasp species, geographic variation drastically modifies this signal through melanic polymorphism potentially driven by different selective pressures. To date, surprisingly little is known about the geographic variation of coloration of social wasps in relation to aposematism and melanism and to genetic and developmental constraints. The main objectives of this study are to improve the description of the colour variation within a social wasp species and to determine which factors are driving this variation. Therefore, we explored the evolutionary history of a polymorphic hornet, Vespa velutina Lepeletier, 1836, using mitochondrial and microsatellite markers, and we analysed its melanic variation using a colour space based on a description of body parts coloration. We found two main lineages within the species and confirmed the previous synonymy of V. auraria Smith, 1852, under V. velutina, differing only by the coloration. We also found that the melanic variation of most body parts was positively correlated, with some segments forming potential colour modules. Finally, we showed that the variation of coloration between populations was not related to their molecular, geographic or climatic differences. Our observations suggest that the coloration patterns of hornets and their geographic variations are determined by genes with an influence of developmental constraints. Our results also highlight that Vespa velutina populations have experienced several convergent evolutions of the coloration, more likely influenced by constraints on aposematism and Müllerian mimicry than by abiotic pressures on melanism. PMID:24740142

  1. Constraints to genetic exchange support gene coadaptation in a tripartite RNA virus.

    PubMed

    Escriu, Fernando; Fraile, Aurora; García-Arenal, Fernando

    2007-01-01

    Genetic exchange by recombination, or reassortment of genomic segments, has been shown to be an important process in RNA virus evolution, resulting often in important phenotypic changes affecting host range and virulence. However, data from numerous systems indicate that reassortant or recombinant genotypes could be selected against in virus populations and suggest that there is coadaptation among viral genes. Little is known about the factors affecting the frequency of reassortants and recombinants along the virus life cycle. We have explored this issue by estimating the frequency of reassortant and recombinant genotypes in experimental populations of Cucumber mosaic virus derived from mixed infections with four different pairs of isolates that differed in about 12% of their nucleotide sequence. Genetic composition of progeny populations were analyzed at various steps of the virus life cycle during host colonization: infection of leaf cells, cell-to-cell movement within the inoculated leaf, encapsidation of progeny genomes, and systemic movement to upper noninoculated leaves. Results indicated that reassortant frequencies do not correspond to random expectations and that selection operates against reassortant genotypes. The intensity of selection, estimated through the use of log-linear models, increased as host colonization progressed. No recombinant was detected in any progeny. Hence, results showed the existence of constraints to genetic exchange linked to various steps of the virus life cycle, so that genotypes with heterologous gene combinations were less fit and disappeared from the population. These results contribute to explain the low frequency of recombinants and reassortants in natural populations of many viruses, in spite of high rates of genetic exchange. More generally, the present work supports the hypothesis of coadaptation of gene complexes within the viral genomes.

  2. Leveraging human genetics to guide drug target discovery.

    PubMed

    Stitziel, Nathan O; Kathiresan, Sekar

    2017-07-01

    Identifying appropriate molecular targets is a critical step in drug development. Despite many advantages, the traditional tools of observational epidemiology and cellular or animal models of disease can be misleading in identifying causal pathways likely to lead to successful therapeutics. Here, we review some favorable aspects of human genetics studies that have the potential to accelerate drug target discovery. These include using genetic studies to identify pathways relevant to human disease, leveraging human genetics to discern causal relationships between biomarkers and disease, and studying genetic variation in humans to predict the potential efficacy and safety of inhibitory compounds aimed at molecular targets. We present some examples taken from studies of plasma lipids and coronary artery disease to highlight how human genetics can accelerate therapeutics development. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Preimplantation genetic diagnosis guided by single-cell genomics

    PubMed Central

    2013-01-01

    Preimplantation genetic diagnosis (PGD) aims to help couples with heritable genetic disorders to avoid the birth of diseased offspring or the recurrence of loss of conception. Following in vitro fertilization, one or a few cells are biopsied from each human preimplantation embryo for genetic testing, allowing diagnosis and selection of healthy embryos for uterine transfer. Although classical methods, including single-cell PCR and fluorescent in situ hybridization, enable PGD for many genetic disorders, they have limitations. They often require family-specific designs and can be labor intensive, resulting in long waiting lists. Furthermore, certain types of genetic anomalies are not easy to diagnose using these classical approaches, and healthy offspring carrying the parental mutant allele(s) can result. Recently, state-of-the-art methods for single-cell genomics have flourished, which may overcome the limitations associated with classical PGD, and these underpin the development of generic assays for PGD that enable selection of embryos not only for the familial genetic disorder in question, but also for various other genetic aberrations and traits at once. Here, we discuss the latest single-cell genomics methodologies based on DNA microarrays, single-nucleotide polymorphism arrays or next-generation sequence analysis. We focus on their strengths, their validation status, their weaknesses and the challenges for implementing them in PGD. PMID:23998893

  4. Imposing nonlinear constraints when estimating genetic and cultural transmission under assortative mating: a simulation study using Mx and BUGS.

    PubMed

    van den Berg, Stéphanie M

    2009-01-01

    Modeling both genetic and cultural transmission in parent-offspring data in the presence of phenotypic assortment requires the imposition of nonlinear constraints. This article reports a simulation study that determined how well the structural equation modeling software package Mx and the Bayesian-oriented BUGS software package can handle such nonlinear constraints under various conditions. Results generally showed good and comparable results for Mx and BUGS, although BUGS was much slower than Mx. However, since BUGS uses Markov-chain Monte Carlo estimation it could be used for parent-offspring models with non-normal data and/or item-response theory models.

  5. Making Sense of Your Genes: A Guide to Genetic Counseling

    MedlinePlus

    ... background (some diseases are more common in certain ethnicities) • Are pregnant and the baby has been diagnosed ... some genetic conditions are more common in certain ethnic groups. What will happen during my appointment? Depending on ...

  6. Introductory Guide to the Statistics of Molecular Genetics

    ERIC Educational Resources Information Center

    Eley, Thalia C.; Rijsdijk, Fruhling

    2005-01-01

    Background: This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association. Methods: Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach. Results: New methods are being developed all…

  7. Guiding Genetic Program Based Data Mining Using Fuzzy Rules

    DTIC Science & Technology

    2006-09-01

    A data mining procedure for automatic determination of fuzzy decision tree structure using a genetic program is discussed. A genetic program (GP) is...an algorithm that evolves other algorithms or mathematical expressions. Methods for accelerating convergence of the data mining procedure are examined...Connections to past GP based data mining procedures for evolving fuzzy decision trees are established. Finally, experimental methods that have been used to validate the data mining algorithm are discussed.

  8. Effects of Hybridization and Evolutionary Constraints on Secondary Metabolites: The Genetic Architecture of Phenylpropanoids in European Populus Species

    PubMed Central

    Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

    2015-01-01

    The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the ‘model forest tree’ Populus. PMID:26010156

  9. Effects of hybridization and evolutionary constraints on secondary metabolites: the genetic architecture of phenylpropanoids in European populus species.

    PubMed

    Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

    2015-01-01

    The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the 'model forest tree' Populus.

  10. A general P300 brain–computer interface presentation paradigm based on performance guided constraints

    PubMed Central

    Townsend, George; Shanahan, Jessica; Ryan, David B.; Sellers, Eric W.

    2013-01-01

    An electroencephalographic-based brain–computer interface (BCI) can provide a non-muscular method of communication. A general model for P300-based BCI stimulus presentations is introduced – the “m choose n” or C(m (number of flashes per sequence), n (number of flashes per item)) paradigm, which is a universal extension of the previously reported checkerboard paradigm (CBP). C(m,n) captures all possible (unconstrained) ways to flash target items, and then applies constraints to enhance ERP’s produced by attended matrix items. We explore a C(36,5) instance of C(m,n) called the “five flash paradigm” (FFP) and compare its performance to the CBP. Eight subjects were tested in each paradigm, counter-balanced. Twelve minutes of calibration data were used as input to a stepwise linear discriminant analysis to derive classification coefficients used for online classification. Accuracy was consistently high for FFP (88%) and CBP (90%); information transfer rate was significantly higher for the FFP (63 bpm) than the CBP (48 bpm). The C(m,n) is a novel and effective general strategy for organizing stimulus groups. Appropriate choices for “m,” “n,” and specific constraints can improve presentation paradigms by adjusting the parameters in a subject specific manner. This may be especially important for people with neuromuscular disabilities. PMID:22960261

  11. Genetic variation and constraints on the evolution of defense against spittlebug (Philaenus spumarius) herbivory in Mimulus guttatus.

    PubMed

    Ivey, C T; Carr, D E; Eubanks, M D

    2009-03-01

    Plants mediate carbon into most ecosystems and are thus under persistent attack by diverse enemies. The evolution of defense against such assaults will depend on the availability of genetic variation, as well as the costs and constraints on defense. We estimated the magnitude of genetic variation for defense against spittlebug (Philaenus spumarius) herbivory in Mimulus guttatus using a diallel cross-grown in a greenhouse. Except for flowering time, additive genetic variation for the plant traits we measured was negligible, regardless of herbivory environment. In contrast, nonadditive genetic variation contributed significantly to all plant traits measured. We found significant additive genetic variation among plants for biomass of adult spittlebugs, suggesting heritability for resistance to herbivory. The other putative resistance trait measured, spittlebug maturation time, was not significantly heritable. We found no evidence for significant genetic variation for tolerance to herbivory except for a small non-nuclear paternal contribution to tolerance for flower number. Additive genetic correlations indicated that more resistant plant genotypes (in terms of adult spittlebug biomass) were also smaller in the absence of spittlebugs, suggesting a potential cost of resistance to herbivory. We found no other significant genetic correlations indicating a cost of defense, nor did we find evidence for a tradeoff between resistance and tolerance to herbivory. Overall, these results suggest the future adaptive evolution of tolerance to spittlebugs in this population will be limited primarily by available genetic variation, whereas the future evolution of antibiosis resistance may be constrained by allocation costs of resistance.

  12. Guided wave constraints on the hydrated low velocity structure of subducting slabs from around the Pacific

    NASA Astrophysics Data System (ADS)

    Garth, T.; Coulson, S.; Rietbrock, A.

    2016-12-01

    Subduction zone guided waves are sensitive to fine scale low velocity structure in the subducting plate, which is not well resolved by other established seismic imaging methods. The low velocity structure of subducting slabs is thought to be primarily related to the hydration of the subducting lithosphere. Studying subduction zone guided waves arrivals can therefore provide new insights into the hydrated structure of subducted slabs, helping to understand the role of fluids in generating Wadati-Benioff zone (WBZ) seismicity, and quantifying the amount of water delivered to the mantle through subduction, as well as revealing the depth to which fluids are delivered. We present guided wave observations and analysis from three subduction zones in the Pacific rim where different ages of oceanic lithosphere is being subducted. Results are presented from the Alaskan-Aleutian, Northern Chile, and Northern Japan subduction zones. Certain features of the low velocity structure, such as a low velocity layer (LVL) at the top of the slab that persists to at least 200km, and low velocity normal faults in the subducted lithospheric mantle, appear to be common in several subduction zone settings. There are however significant variations in the thickness of the LVL, and character of hydrated faults, suggesting significant variations in the hydration of the subducting lithosphere. The LVL is interpreted as metastable oceanic crust, and appears to be thicker in older subducted slabs (e.g. 8 km thick in Northern Japan), than in the younger crust subducted slabs (e.g. 1-2 km beneath South America). The lithospheric mantle also appears to be more highly hydrated in the older subducting lithosphere (e.g. 2.0 - 3.5 wt% hydrated beneath Northern Japan) than in the younger subducted slabs (e.g. 0.6 - 1.9 wt% beneath South America). Coupled with the thicker WBZ seen in the older subducting material, this suggests that older subducting material is able to carry more water to the deeper mantle

  13. Autism spectrum disorders: an updated guide for genetic counseling.

    PubMed

    Griesi-Oliveira, Karina; Sertié, Andréa Laurato

    2017-01-01

    Autism spectrum disorder is a complex and genetically heterogeneous disorder, which has hampered the identification of the etiological factors in each patient and, consequently, the genetic counseling for families at risk. However, in the last decades, the remarkable advances in the knowledge of genetic aspects of autism based on genetic and molecular research, as well as the development of new molecular diagnostic tools, have substantially changed this scenario. Nowadays, it is estimated that using the currently available molecular tests, a potential underlying genetic cause can be identified in nearly 25% of cases. Combined with clinical assessment, prenatal history evaluation and investigation of other physiological aspects, an etiological explanation for the disease can be found for approximately 30 to 40% of patients. Therefore, in view of the current knowledge about the genetic architecture of autism spectrum disorder, which has contributed for a more precise genetic counseling, and of the potential benefits that an etiological investigation can bring to patients and families, molecular genetic investigation has become increasingly important. Here, we discuss the current view of the genetic architecture of autism spectrum disorder, and list the main associated genetic alterations, the available molecular tests and the key aspects for the genetic counseling of these families. RESUMO O transtorno do espectro autista é um distúrbio complexo e geneticamente heterogêneo, o que sempre dificultou a identificação de sua etiologia em cada paciente em particular e, por consequência, o aconselhamento genético das famílias. Porém, nas últimas décadas, o acúmulo crescente de conhecimento oriundo das pesquisas sobre os aspectos genéticos e moleculares desta doença, assim como o desenvolvimento de novas ferramentas de diagnóstico molecular, tem mudado este cenário de forma substancial. Atualmente, estima-se que, por meio de testes moleculares, é poss

  14. A Guide to Selected National Genetic Voluntary Organizations.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    The directory lists approximately 120 mutual support groups concerned with the medical and psychological impacts of genetic disorders and birth defects on individuals and their families. The groups are dedicated to serving the ongoing emotional, practical, and financial needs of these populations. The entries are arranged alphabetically and…

  15. A Guide to Selected National Genetic Voluntary Organizations.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    The directory lists mutual support groups concerned with the medical and psychosocial impacts of genetic disorders and birth defects on affected individuals and families. Each organization included is dedicated to the ongoing emotional, practical, and financial needs of these populations. Entries are categorized by disorder, including: general,…

  16. Pushing the P300-based brain-computer interface beyond 100 bpm: extending performance guided constraints into the temporal domain.

    PubMed

    Townsend, G; Platsko, V

    2016-04-01

    A new presentation paradigm for the P300-based brain-computer interface (BCI) referred to as the 'asynchronous paradigm' (ASP) is introduced and studied. It is based on the principle of performance guided constraints (Townsend et al 2012 Neurosci. Lett. 531 63-8) extended from the spatial domain into the temporal domain. The traditional constraint of flashing targets in predefined constant epochs of time is eliminated and targets flash asynchronously with timing based instead on constraints intended to improve performance. We propose appropriate temporal constraints to derive the ASP and compare its performance to that of the 'checkerboard paradigm' (CBP), which has previously been shown to be superior to the standard 'row/column paradigm' introduced by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). Ten participants were tested in the ASP and CBP conditions both with traditional flashing items and with flashing faces in place of the targets (see Zhang et al 2012 J. Neural Eng. 9 026018; Kaufmann and Kübler 2014 J. Neural Eng. 11 ; Chen et al 2015 J. Neurosci. Methods 239 18-27). Eleven minutes of calibration data were used as input to a stepwise linear discriminant analysis to derive classification coefficients used for online classification. Accuracy was consistently high for both paradigms (87% and 93%) while information transfer rate was 45% higher for the ASP than the CBP. In a free spelling task, one subject spelled a 66 character sentence (from a 72 item matrix) with 100% accuracy in 3 min and 24 s demonstrating a practical throughput of 120 bits per minute (bpm) with a theoretical upper bound of 258 bpm. The subject repeated the task three times in a row without error. This work represents an advance in P300 speller technology and raises the ceiling that was being reached on P300-based BCIs. Most importantly, the research presented here is a novel and effective general strategy for organising timing for flashing items. The ASP

  17. Caenorhabditis elegans: A Genetic Guide to Parasitic Nematode Biology.

    PubMed

    Bird, D M; Opperman, C H

    1998-09-01

    The advent of parasite genome sequencing projects, as well as an increase in biology-directed gene discovery, promises to reveal genes encoding many of the key molecules required for nematode-host interactions. However, distinguishing parasitism genes from those merely required for nematode viability remains a substantial challenge. Although this will ultimately require a functional test in the host or parasite, the free-living nematode Caenorhabditis elegans can be exploited as a heterologous system to determine function of candidate parasitism genes. Studies of C. elegans also have revealed genetic networks, such as the dauer pathway, that may also be important adaptations for parasitism. As a more directed means of identifying parasitism traits, we developed classical genetics for Heterodera glycines and have used this approach to map genes conferring host resistance-breaking phenotypes. It is likely that the C. elegans and H. glycines genomes will be at least partially syntenic, thus permitting predictive physical mapping of H. glycines genes of interest.

  18. Initialization Method for Grammar-Guided Genetic Programming

    NASA Astrophysics Data System (ADS)

    García-Arnau, M.; Manrique, D.; Ríos, J.; Rodríguez-Patón, A.

    This paper proposes a new tree-generation algorithm for grammarguided genetic programming that includes a parameter to control the maximum size of the trees to be generated. An important feature of this algorithm is that the initial populations generated are adequately distributed in terms of tree size and distribution within the search space. Consequently, genetic programming systems starting from the initial populations generated by the proposed method have a higher convergence speed. Two different problems have been chosen to carry out the experiments: a laboratory test involving searching for arithmetical equalities and the real-world task of breast cancer prognosis. In both problems, comparisons have been made to another five important initialization methods.

  19. RNA-guided genetic silencing systems in bacteria and archaea.

    PubMed

    Wiedenheft, Blake; Sternberg, Samuel H; Doudna, Jennifer A

    2012-02-15

    Clustered regularly interspaced short palindromic repeat (CRISPR) are essential components of nucleic-acid-based adaptive immune systems that are widespread in bacteria and archaea. Similar to RNA interference (RNAi) pathways in eukaryotes, CRISPR-mediated immune systems rely on small RNAs for sequence-specific detection and silencing of foreign nucleic acids, including viruses and plasmids. However, the mechanism of RNA-based bacterial immunity is distinct from RNAi. Understanding how small RNAs are used to find and destroy foreign nucleic acids will provide new insights into the diverse mechanisms of RNA-controlled genetic silencing systems.

  20. Specific immunotherapy by genetically engineered APCs: the "guided missile" strategy.

    PubMed

    Wu, B; Wu, J M; Miagkov, A; Adams, R N; Levitsky, H I; Drachman, D B

    2001-04-01

    We tested the hypothesis that APCs genetically engineered to present an Ag and to express Fas ligand (FasL) simultaneously can target and eliminate Ag-specific T cells. Transgenic T cells specific for influenza hemagglutinin (HA) were used as targets. We prepared recombinant vaccinia virus vectors (VVV) to transfer the gene constructs individually or simultaneously into APCs. We prevented unwanted viral replication by attenuating the VVVs with psoralen-UV light treatment. For presentation of the HA Ag, APCs were transduced with cDNA for HA flanked by sequences of the lysosome-associated membrane protein that direct efficient processing and presentation of the Ag by APCs. As a "warhead" for the APCs, we transduced them with the gene for FasL, which induces apoptosis of Fas-expressing activated T cells. To protect the transduced APCs from self-destruction by FasL, we transferred cDNA for a truncated form of Fas-associated death domain, which inhibits Fas-mediated cell death. Our results show that the engineered APCs effectively expressed the genes of interest. APCs transduced with VVV carrying all three gene constructs specifically killed HA-transgenic T cells in culture. Coculture with T cells specific for an unrelated Ag (OVA) had no significant effect. Our in vitro findings show that APCs can be genetically engineered to target and kill Ag-specific T cells and represent a promising novel strategy for the specific treatment of autoimmune diseases.

  1. The prospect of genome-guided preventive medicine: a need and opportunity for genetic counselors.

    PubMed

    O'Daniel, Julianne M

    2010-08-01

    One of the major anticipated benefits of genomic medicine is the area of preventive medicine. Commercially available genomic profiling is now able to generate risk information for a number of common conditions several of which have recognized preventive guidelines. Similarly, family history assessment affords powerful health risk prediction based on the shared genetic, physical and lifestyle environments within families. Thus, with the ability to help predict disease risk and enable preemptive health plans, genome-guided preventive medicine has the potential to improve population health on an individualized level. To realize this potential, steps to broaden access to accurate genomic health information must be considered. With expertise in genetic science, risk assessment and communication, and a patient-centered practice approach, genetic counselors are poised to play a critical role in facilitating the incorporation of genomic health risks into the burgeoning field of genome-guided preventive medicine.

  2. Genome evolution is driven by gene expression-generated biophysical constraints through RNA-directed genetic variation: A hypothesis.

    PubMed

    Auboeuf, Didier

    2017-10-01

    The biogenesis of RNAs and proteins is a threat to the cell. Indeed, the act of transcription and nascent RNAs challenge DNA stability. Both RNAs and nascent proteins can also initiate the formation of toxic aggregates because of their physicochemical properties. In reviewing the literature, I show that co-transcriptional and co-translational biophysical constraints can trigger DNA instability that in turn increases the likelihood that sequences that alleviate the constraints emerge over evolutionary time. These directed genetic variations rely on the biogenesis of small RNAs that are transcribed directly from challenged DNA regions or processed from the transcripts that directly or indirectly generate constraints or aggregates. These small RNAs can then target the genomic regions from which they initially originate and increase the local mutation rate of the targeted loci. This mechanism is based on molecular pathways involved in anti-parasite genome defence systems, and implies that gene expression-related biophysical constraints represent a driving force of genome evolution. © 2017 The Authors. BioEssays Published by Wiley Periodicals, Inc.

  3. Constraints imposed by the membrane selectively guide the alternating access dynamics of the glutamate transporter GltPh.

    PubMed

    Lezon, Timothy R; Bahar, Ivet

    2012-03-21

    Substrate transport in sodium-coupled amino acid symporters involves a large-scale conformational change that shifts the access to the substrate-binding site from one side of the membrane to the other. The structural change is particularly substantial and entails a unique piston-like quaternary rearrangement in glutamate transporters, as evidenced by the difference between the outward-facing and inward-facing structures resolved for the archaeal aspartate transporter Glt(Ph). These structural changes occur over time and length scales that extend beyond the reach of current fully atomic models, but are regularly explored with the use of elastic network models (ENMs). Despite their success with other membrane proteins, ENM-based approaches for exploring the collective dynamics of Glt(Ph) have fallen short of providing a plausible mechanism. This deficiency is attributed here to the anisotropic constraints imposed by the membrane, which are not incorporated into conventional ENMs. Here we employ two novel (to our knowledge) ENMs to demonstrate that one can largely capture the experimentally observed structural change using only the few lowest-energy modes of motion that are intrinsically accessible to the transporter, provided that the surrounding lipid molecules are incorporated into the ENM. The presence of the membrane reduces the overall energy of the transition compared with conventional models, showing that the membrane not only guides the selected mechanism but also acts as a facilitator. Finally, we show that the dynamics of Glt(Ph) is biased toward transitions of individual subunits of the trimer rather than cooperative transitions of all three subunits simultaneously, suggesting a mechanism of transport that exploits the intrinsic dynamics of individual subunits. Our software is available online at http://www.membranm.csb.pitt.edu. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. The genetics of phaeochromocytoma: using clinical features to guide genetic testing.

    PubMed

    Jafri, Mariam; Maher, Eamonn R

    2012-02-01

    Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by endocrinologists. Over the last decade, major advances have been made in understanding the molecular genetic basis of adrenal and extra-adrenal phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra-adrenal functional paraganglioma (eFPGL)). In contrast to the previously held belief that only 10% of cases had a genetic component, currently about one-third of all aPCA/eFPGL cases are thought to be attributable to germline mutations in at least nine genes (NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, MAX and VHL). Recognition of inherited cases of aPCA/eFPGL is critical for optimal patient management. Thus, the identification of a germline mutation can predict risks of malignancy, recurrent disease, associated non-chromaffin tumours and risks to other family members. Mutation carriers should be offered specific surveillance programmes (according to the relevant gene). In this review, we will describe the genetics of aPCA/eFPGL and strategies for genetic testing.

  5. EDGA: A Population Evolution Direction-Guided Genetic Algorithm for Protein-Ligand Docking.

    PubMed

    Guan, Boxin; Zhang, Changsheng; Ning, Jiaxu

    2016-07-01

    Protein-ligand docking can be formulated as a search algorithm associated with an accurate scoring function. However, most current search algorithms cannot show good performance in docking problems, especially for highly flexible docking. To overcome this drawback, this article presents a novel and robust optimization algorithm (EDGA) based on the Lamarckian genetic algorithm (LGA) for solving flexible protein-ligand docking problems. This method applies a population evolution direction-guided model of genetics, in which search direction evolves to the optimum solution. The method is more efficient to find the lowest energy of protein-ligand docking. We consider four search methods-a tradition genetic algorithm, LGA, SODOCK, and EDGA-and compare their performance in docking of six protein-ligand docking problems. The results show that EDGA is the most stable, reliable, and successful.

  6. Differentiation of persistent anatomical defensive structures is costly and determined by nutrient availability and genetic growth-defence constraints.

    PubMed

    Moreira, Xoaquín; Zas, Rafael; Solla, Alejandro; Sampedro, Luis

    2015-02-01

    Conifers exhibit a number of chemical and anatomical mechanisms to defend against pests and pathogens. Theory predicts an increased investment in plant defences under limited nutrient availability, but while this has been demonstrated for chemical defences, it has rarely been shown for anatomical defensive structures. In a long-lived woody plant, we tested the hypothesis that limited nutrient availability may promote an improved differentiation of persistent anatomical defences. We also hypothesized that the costs of differentiation of those long-term anatomical structures may be determined by genetic constraints on early growth potential. Using Pinus pinaster Ait. juveniles, we performed a greenhouse study with 15 half-sib families subjected to experimental manipulation of phosphorus (P) availability and herbivory-related induced responses. When plants were ∼30 cm high, half of the plant material was treated with methyl jasmonate to induce defences, and 2 weeks later plants were harvested and the abundance of resin canals in the cortex and xylem was assessed. Density of constitutive resin canals in the cortex and the total canal system was ∼1.5-fold higher in plants under limited P availability than in fully fertilized plants. Availability of P did not significantly influence the inducibility of resin canal traits. We found negative genetic correlations between plant growth and the density of constitutive canals in the xylem and total canal system, but only under conditions of limited nutrition. These results demonstrate for the first time that differentiation of constitutive anatomical-based defences is affected by P limitation. Moreover, results also evidence the existence of genetic constraints between plant growth and constitutive defensive investment, where lineages with the highest growth potential showed the lowest investment in constitutive resin canals.

  7. A Study of Penalty Function Methods for Constraint Handling with Genetic Algorithm

    NASA Technical Reports Server (NTRS)

    Ortiz, Francisco

    2004-01-01

    COMETBOARDS (Comparative Evaluation Testbed of Optimization and Analysis Routines for Design of Structures) is a design optimization test bed that can evaluate the performance of several different optimization algorithms. A few of these optimization algorithms are the sequence of unconstrained minimization techniques (SUMT), sequential linear programming (SLP) and the sequential quadratic programming techniques (SQP). A genetic algorithm (GA) is a search technique that is based on the principles of natural selection or "survival of the fittest". Instead of using gradient information, the GA uses the objective function directly in the search. The GA searches the solution space by maintaining a population of potential solutions. Then, using evolving operations such as recombination, mutation and selection, the GA creates successive generations of solutions that will evolve and take on the positive characteristics of their parents and thus gradually approach optimal or near-optimal solutions. By using the objective function directly in the search, genetic algorithms can be effectively applied in non-convex, highly nonlinear, complex problems. The genetic algorithm is not guaranteed to find the global optimum, but it is less likely to get trapped at a local optimum than traditional gradient-based search methods when the objective function is not smooth and generally well behaved. The purpose of this research is to assist in the integration of genetic algorithm (GA) into COMETBOARDS. COMETBOARDS cast the design of structures as a constrained nonlinear optimization problem. One method used to solve constrained optimization problem with a GA to convert the constrained optimization problem into an unconstrained optimization problem by developing a penalty function that penalizes infeasible solutions. There have been several suggested penalty function in the literature each with there own strengths and weaknesses. A statistical analysis of some suggested penalty functions

  8. Experimental evolution for generalists and specialists reveals multivariate genetic constraints on thermal reaction norms.

    PubMed

    Berger, D; Walters, R J; Blanckenhorn, W U

    2014-09-01

    Theory predicts the emergence of generalists in variable environments and antagonistic pleiotropy to favour specialists in constant environments, but empirical data seldom support such generalist-specialist trade-offs. We selected for generalists and specialists in the dung fly Sepsis punctum (Diptera: Sepsidae) under conditions that we predicted would reveal antagonistic pleiotropy and multivariate trade-offs underlying thermal reaction norms for juvenile development. We performed replicated laboratory evolution using four treatments: adaptation at a hot (31 °C) or a cold (15 °C) temperature, or under regimes fluctuating between these temperatures, either within or between generations. After 20 generations, we assessed parental effects and genetic responses of thermal reaction norms for three correlated life-history traits: size at maturity, juvenile growth rate and juvenile survival. We find evidence for antagonistic pleiotropy for performance at hot and cold temperatures, and a temperature-mediated trade-off between juvenile survival and size at maturity, suggesting that trade-offs associated with environmental tolerance can arise via intensified evolutionary compromises between genetically correlated traits. However, despite this antagonistic pleiotropy, we found no support for the evolution of increased thermal tolerance breadth at the expense of reduced maximal performance, suggesting low genetic variance in the generalist-specialist dimension.

  9. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

    SciTech Connect

    Torella, JP; Boehm, CR; Lienert, F; Chen, JH; Way, JC; Silver, PA

    2013-12-28

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.

  10. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

    PubMed Central

    Torella, Joseph P.; Boehm, Christian R.; Lienert, Florian; Chen, Jan-Hung; Way, Jeffrey C.; Silver, Pamela A.

    2014-01-01

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates. PMID:24078086

  11. Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design.

    PubMed

    Albanaz, Amanda T S; Rodrigues, Carlos H M; Pires, Douglas E V; Ascher, David B

    2017-06-01

    Mutations introduce diversity into genomes, leading to selective changes and driving evolution. These changes have contributed to the emergence of many of the current major health concerns of the 21st century, from the development of genetic diseases and cancers to the rise and spread of drug resistance. The experimental systematic testing of all mutations in a system of interest is impractical and not cost-effective, which has created interest in the development of computational tools to understand the molecular consequences of mutations to aid and guide rational experimentation. Areas covered: Here, the authors discuss the recent development of computational methods to understand the effects of coding mutations to protein function and interactions, particularly in the context of the 3D structure of the protein. Expert opinion: While significant progress has been made in terms of innovative tools to understand and quantify the different range of effects in which a mutation or a set of mutations can give rise to a phenotype, a great gap still exists when integrating these predictions and drawing causality conclusions linking variants. This often requires a detailed understanding of the system being perturbed. However, as part of the drug development process it can be used preemptively in a similar fashion to pharmacokinetics predictions, to guide development of therapeutics to help guide the design and analysis of clinical trials, patient treatment and public health policy strategies.

  12. Genetic algorithms-based inversion of multimode guided waves for cortical bone characterization

    NASA Astrophysics Data System (ADS)

    Bochud, N.; Vallet, Q.; Bala, Y.; Follet, H.; Minonzio, J.-G.; Laugier, P.

    2016-10-01

    Recent progress in quantitative ultrasound has exploited the multimode waveguide response of long bones. Measurements of the guided modes, along with suitable waveguide modeling, have the potential to infer strength-related factors such as stiffness (mainly determined by cortical porosity) and cortical thickness. However, the development of such model-based approaches is challenging, in particular because of the multiparametric nature of the inverse problem. Current estimation methods in the bone field rely on a number of assumptions for pairing the incomplete experimental data with the theoretical guided modes (e.g. semi-automatic selection and classification of the data). The availability of an alternative inversion scheme that is user-independent is highly desirable. Thus, this paper introduces an efficient inversion method based on genetic algorithms using multimode guided waves, in which the mode-order is kept blind. Prior to its evaluation on bone, our proposal is validated using laboratory-controlled measurements on isotropic plates and bone-mimicking phantoms. The results show that the model parameters (i.e. cortical thickness and porosity) estimated from measurements on a few ex vivo human radii are in good agreement with the reference values derived from x-ray micro-computed tomography. Further, the cortical thickness estimated from in vivo measurements at the third from the distal end of the radius is in good agreement with the values delivered by site-matched high-resolution x-ray peripheral computed tomography.

  13. Lakeview uranium area, Lake County, Oregon - constraints on genetic modelling from a district-scale perspective

    SciTech Connect

    Weissenburger, K.W.

    1984-01-01

    Extent-of-outcrop geologic mapping (1:12,000) on the Cox Flat 7.5-minute quadrangle establishes the stratigraphy and structure near the White King uranium mine, about 25 km northwest of Lakeview, Lake County, Oregon. Bedrock includes an Oligocene andesitic volcanic/sedimentary section, four late Oligocene rhyodacitic ignimbrite sequences, a late Oligocene/Miocene tuffaceous section, locally thick early to late Miocene basaltic flows, and an interbedded sequence of late Miocene (about 7-8 Ma old) felsic tuffs and thin basalt flows. Relatively intense down-to-the northeast normal faulting and southwestward stratal tilting resulted from a pre-Basin-and-Range extensional tectonic regime with an ENE least-principal stress orientation. This faulting and tilting began after the late Oligocene ignimbrite volcanism and before the spread of Coleman Rim-equivalent basalt flows. The interpreted geology constrains genetic models, resource estimates, and exploration strategies for uranium occurrences in the Lakeview area. Fault- and fracture-controlled hydrothermal uranium deposits are restricted to favorable stratigraphic horizons of the Miocene section with the important exception of porous and permeable upper portions of the late Oligocene section. Previous models have stressed the importance of intrusive rhyolite plug domes as sources of uranium and/or heat in ore genesis and targeted exploration efforts at dome contacts. Mass balance and other arguments show that an association with rhyolite domes is not a necessary criterion for ore formation or exploration.

  14. DeMAID/GA USER'S GUIDE Design Manager's Aid for Intelligent Decomposition with a Genetic Algorithm

    NASA Technical Reports Server (NTRS)

    Rogers, James L.

    1996-01-01

    Many companies are looking for new tools and techniques to aid a design manager in making decisions that can reduce the time and cost of a design cycle. One tool that is available to aid in this decision making process is the Design Manager's Aid for Intelligent Decomposition (DeMAID). Since the initial release of DEMAID in 1989, numerous enhancements have been added to aid the design manager in saving both cost and time in a design cycle. The key enhancement is a genetic algorithm (GA) and the enhanced version is called DeMAID/GA. The GA orders the sequence of design processes to minimize the cost and time to converge to a solution. These enhancements as well as the existing features of the original version of DEMAID are described. Two sample problems are used to show how these enhancements can be applied to improve the design cycle. This report serves as a user's guide for DeMAID/GA.

  15. Financial constraints in capacity planning: a national utility regulatory model (NUREG). Volume II of III: user's guide. Final report

    SciTech Connect

    Not Available

    1981-10-29

    This volume is a User's Guide to the National Utility Regulatory Model (NUREG) and its implementation of the National Coal Model. This is the second of three volumes provided by ICF under contract number DEAC-01-79EI-10579. These three volumes are: a manual describing the NUREG methodology; a users guide; and a description of the software. This manual provides a brief introduction to the National Utility Regulation Model, describes the various programs that comprise the National Utility Regulatory Model, gives sample input files, and provides information needed to run the model.

  16. Breast cancer: determining the genetic profile from ultrasound-guided percutaneous biopsy specimens obtained during the diagnostic workups.

    PubMed

    López Ruiz, J A; Zabalza Estévez, I; Mieza Arana, J A

    2016-01-01

    To evaluate the possibility of determining the genetic profile of primary malignant tumors of the breast from specimens obtained by ultrasound-guided percutaneous biopsies during the diagnostic imaging workup. This is a retrospective study in 13 consecutive patients diagnosed with invasive breast cancer by B-mode ultrasound-guided 12 G core needle biopsy. After clinical indication, the pathologist decided whether the paraffin block specimens seemed suitable (on the basis of tumor size, validity of the sample, and percentage of tumor cells) before sending them for genetic analysis with the MammaPrint® platform. The size of the tumors on ultrasound ranged from 0.6cm to 5cm. In 11 patients the preserved specimen was considered valid and suitable for use in determining the genetic profile. In 1 patient (with a 1cm tumor) the pathologist decided that it was necessary to repeat the core biopsy to obtain additional samples. In 1 patient (with a 5cm tumor) the specimen was not considered valid by the genetic laboratory. The percentage of tumor cells in the samples ranged from 60% to 70%. In 11/13 cases (84.62%) it was possible to do the genetic analysis on the previously diagnosed samples. In most cases, regardless of tumor size, it is possible to obtain the genetic profile from tissue specimens obtained with ultrasound-guided 12 G core biopsy preserved in paraffin blocks. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  17. A Bee Evolutionary Guiding Nondominated Sorting Genetic Algorithm II for Multiobjective Flexible Job-Shop Scheduling

    PubMed Central

    Deng, Qianwang; Gong, Xuran; Zhang, Like; Liu, Wei; Ren, Qinghua

    2017-01-01

    Flexible job-shop scheduling problem (FJSP) is an NP-hard puzzle which inherits the job-shop scheduling problem (JSP) characteristics. This paper presents a bee evolutionary guiding nondominated sorting genetic algorithm II (BEG-NSGA-II) for multiobjective FJSP (MO-FJSP) with the objectives to minimize the maximal completion time, the workload of the most loaded machine, and the total workload of all machines. It adopts a two-stage optimization mechanism during the optimizing process. In the first stage, the NSGA-II algorithm with T iteration times is first used to obtain the initial population N, in which a bee evolutionary guiding scheme is presented to exploit the solution space extensively. In the second stage, the NSGA-II algorithm with GEN iteration times is used again to obtain the Pareto-optimal solutions. In order to enhance the searching ability and avoid the premature convergence, an updating mechanism is employed in this stage. More specifically, its population consists of three parts, and each of them changes with the iteration times. What is more, numerical simulations are carried out which are based on some published benchmark instances. Finally, the effectiveness of the proposed BEG-NSGA-II algorithm is shown by comparing the experimental results and the results of some well-known algorithms already existed. PMID:28458687

  18. A Bee Evolutionary Guiding Nondominated Sorting Genetic Algorithm II for Multiobjective Flexible Job-Shop Scheduling.

    PubMed

    Deng, Qianwang; Gong, Guiliang; Gong, Xuran; Zhang, Like; Liu, Wei; Ren, Qinghua

    2017-01-01

    Flexible job-shop scheduling problem (FJSP) is an NP-hard puzzle which inherits the job-shop scheduling problem (JSP) characteristics. This paper presents a bee evolutionary guiding nondominated sorting genetic algorithm II (BEG-NSGA-II) for multiobjective FJSP (MO-FJSP) with the objectives to minimize the maximal completion time, the workload of the most loaded machine, and the total workload of all machines. It adopts a two-stage optimization mechanism during the optimizing process. In the first stage, the NSGA-II algorithm with T iteration times is first used to obtain the initial population N, in which a bee evolutionary guiding scheme is presented to exploit the solution space extensively. In the second stage, the NSGA-II algorithm with GEN iteration times is used again to obtain the Pareto-optimal solutions. In order to enhance the searching ability and avoid the premature convergence, an updating mechanism is employed in this stage. More specifically, its population consists of three parts, and each of them changes with the iteration times. What is more, numerical simulations are carried out which are based on some published benchmark instances. Finally, the effectiveness of the proposed BEG-NSGA-II algorithm is shown by comparing the experimental results and the results of some well-known algorithms already existed.

  19. In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

    PubMed

    Pick, J L; Hutter, P; Tschirren, B

    2016-06-01

    Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.

  20. Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records

    PubMed Central

    2011-01-01

    Background Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results. Discussion As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use. Summary This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications. PMID:22047175

  1. Rotational-slice-Based prostate segmentation using level set with shape constraint for 3D end-firing TRUS guided biopsy.

    PubMed

    Qiu, Wu; Yuan, Jing; Ukwatta, Eranga; Tessier, David; Fenster, Aaron

    2012-01-01

    Prostate segmentation in 3D ultrasound images is an important step in the planning and treatment of 3D end-firing transrectal ultrasound (TRUS) guided prostate biopsy. A semi-automatic prostate segmentation method is presented in this paper, which integrates a modified distance regularization level set formulation with shape constraint to a rotational-slice-based 3D prostate segmentation method. Its performance, using different metrics, has been evaluated on a set of twenty 3D patient prostate images by comparison with expert delineations. The volume overlap ratio of 93.39 +/- 1.26% and the mean absolute surface distance of 1.16 +/- 0.34 mm were found in the quantitative validation result.

  2. Evolutionary constraints of warning signals: A genetic trade-off between the efficacy of larval and adult warning coloration can maintain variation in signal expression.

    PubMed

    Lindstedt, C; Schroderus, E; Lindström, L; Mappes, T; Mappes, J

    2016-11-01

    To predict evolutionary responses of warning signals under selection, we need to determine the inheritance pattern of the signals, and how they are genetically correlated with other traits contributing to fitness. Furthermore, protective coloration often undergoes remarkable changes within an individual's lifecycle, requiring us to quantify the genetic constraints of adaptive coloration across all the relevant life stages. Based on a 12 generation pedigree with > 11,000 individuals of the wood tiger moth (Arctia plantaginis), we show that high primary defense as a larva (large warning signal) results in weaker defenses as adult (less efficient warning color), due to the negative genetic correlation between the efficacy of larval and adult warning coloration. However, production of effective warning coloration as a larva did not incur any life-history costs and was positively genetically correlated with reproductive output. These results provide novel insights into the evolutionary constraints on protective coloration in animals, and explain the maintenance of variation in the signal expression despite the strong directional selection by predators. By analyzing the genetic and environmental effects on warning signal and life-history traits in all relevant life stages, we can accurately determine the mechanisms shaping the evolutionary responses of phenotypic traits under different selection environments.

  3. Constraints, independence, and evolution of thermal plasticity: probing genetic architecture of long- and short-term thermal acclimation.

    PubMed

    Gerken, Alison R; Eller, Olivia C; Hahn, Daniel A; Morgan, Theodore J

    2015-04-07

    Seasonal and daily thermal variation can limit species distributions because of physiological tolerances. Low temperatures are particularly challenging for ectotherms, which use both basal thermotolerance and acclimation, an adaptive plastic response, to mitigate thermal stress. Both basal thermotolerance and acclimation are thought to be important for local adaptation and persistence in the face of climate change. However, the evolutionary independence of basal and plastic tolerances remains unclear. Acclimation can occur over longer (seasonal) or shorter (hours to days) time scales, and the degree of mechanistic overlap is unresolved. Using a midlatitude population of Drosophila melanogaster, we show substantial heritable variation in both short- and long-term acclimation. Rapid cold hardening (short-term plasticity) and developmental acclimation (long-term plasticity) are positively correlated, suggesting shared mechanisms. However, there are independent components of these traits, because developmentally acclimated flies respond positively to short-term acclimation. A strong negative correlation between basal cold tolerance and developmental acclimation suggests that basal cold tolerance may constrain developmental acclimation, whereas a weaker negative correlation between basal cold tolerance and short-term acclimation suggests less constraint. Using genome-wide association mapping, we show the genetic architecture of rapid cold hardening and developmental acclimation responses are nonoverlapping at the SNP and corresponding gene level. However, genes associated with each trait share functional similarities, including genes involved in apoptosis and autophagy, cytoskeletal and membrane structural components, and ion binding and transport. These results indicate substantial opportunity for short-term and long-term acclimation responses to evolve separately from each other and for short-term acclimation to evolve separately from basal thermotolerance.

  4. Space tug thermal control equipment thermal requirements, characteristics, and constraints catalogue: Users guide. [spacecraft thermal control components

    NASA Technical Reports Server (NTRS)

    Ward, T. L.

    1974-01-01

    This manual details the input instructions to the data bank, and explanation of the program and its output. The data bank was developed in satisfaction of two of the study tasks, the equipment thermal requirement catalog and the equipment characteristics and constraints catalog. The data bank contains 109 components within space tug avionics system. Other systems were not included in the data bank due to the available information, however, with some program modification, other systems could be incorporated into the data bank program. The data bank was developed and checked out and is compatible with the Univac 1108, and the CDC 6500 operating systems. The data contained in the data bank is general in content with emphasis on the component thermal design. The data is applicable to any spacecraft program where the components contained in the data bank can be applied in satisfaction of the system and subsystem requirements.

  5. Multi-View Budgeted Learning under Label and Feature Constraints Using Label-Guided Graph-Based Regularization

    SciTech Connect

    Symons, Christopher T; Arel, Itamar

    2011-01-01

    Budgeted learning under constraints on both the amount of labeled information and the availability of features at test time pertains to a large number of real world problems. Ideas from multi-view learning, semi-supervised learning, and even active learning have applicability, but a common framework whose assumptions fit these problem spaces is non-trivial to construct. We leverage ideas from these fields based on graph regularizers to construct a robust framework for learning from labeled and unlabeled samples in multiple views that are non-independent and include features that are inaccessible at the time the model would need to be applied. We describe examples of applications that fit this scenario, and we provide experimental results to demonstrate the effectiveness of knowledge carryover from training-only views. As learning algorithms are applied to more complex applications, relevant information can be found in a wider variety of forms, and the relationships between these information sources are often quite complex. The assumptions that underlie most learning algorithms do not readily or realistically permit the incorporation of many of the data sources that are available, despite an implicit understanding that useful information exists in these sources. When multiple information sources are available, they are often partially redundant, highly interdependent, and contain noise as well as other information that is irrelevant to the problem under study. In this paper, we are focused on a framework whose assumptions match this reality, as well as the reality that labeled information is usually sparse. Most significantly, we are interested in a framework that can also leverage information in scenarios where many features that would be useful for learning a model are not available when the resulting model will be applied. As with constraints on labels, there are many practical limitations on the acquisition of potentially useful features. A key difference in the

  6. Rendering-based video-CT registration with physical constraints for image-guided endoscopic sinus surgery

    NASA Astrophysics Data System (ADS)

    Otake, Y.; Leonard, S.; Reiter, A.; Rajan, P.; Siewerdsen, J. H.; Ishii, M.; Taylor, R. H.; Hager, G. D.

    2015-03-01

    We present a system for registering the coordinate frame of an endoscope to pre- or intra- operatively acquired CT data based on optimizing the similarity metric between an endoscopic image and an image predicted via rendering of CT. Our method is robust and semi-automatic because it takes account of physical constraints, specifically, collisions between the endoscope and the anatomy, to initialize and constrain the search. The proposed optimization method is based on a stochastic optimization algorithm that evaluates a large number of similarity metric functions in parallel on a graphics processing unit. Images from a cadaver and a patient were used for evaluation. The registration error was 0.83 mm and 1.97 mm for cadaver and patient images respectively. The average registration time for 60 trials was 4.4 seconds. The patient study demonstrated robustness of the proposed algorithm against a moderate anatomical deformation.

  7. On the use of genetic algorithm to optimize industrial assets lifecycle management under safety and budget constraints

    SciTech Connect

    Lonchampt, J.; Fessart, K.

    2013-07-01

    The purpose of this paper is to describe the method and tool dedicated to optimize investments planning for industrial assets. These investments may either be preventive maintenance tasks, asset enhancements or logistic investments such as spare parts purchases. The two methodological points to investigate in such an issue are: 1. The measure of the profitability of a portfolio of investments 2. The selection and planning of an optimal set of investments 3. The measure of the risk of a portfolio of investments The measure of the profitability of a set of investments in the IPOP tool is synthesised in the Net Present Value indicator. The NPV is the sum of the differences of discounted cash flows (direct costs, forced outages...) between the situations with and without a given investment. These cash flows are calculated through a pseudo-Markov reliability model representing independently the components of the industrial asset and the spare parts inventories. The component model has been widely discussed over the years but the spare part model is a new one based on some approximations that will be discussed. This model, referred as the NPV function, takes for input an investments portfolio and gives its NPV. The second issue is to optimize the NPV. If all investments were independent, this optimization would be an easy calculation, unfortunately there are two sources of dependency. The first one is introduced by the spare part model, as if components are indeed independent in their reliability model, the fact that several components use the same inventory induces a dependency. The second dependency comes from economic, technical or logistic constraints, such as a global maintenance budget limit or a safety requirement limiting the residual risk of failure of a component or group of component, making the aggregation of individual optimum not necessary feasible. The algorithm used to solve such a difficult optimization problem is a genetic algorithm. After a description

  8. The 2005 USDA Food Guide Pyramid is associated with more adequate nutrient intakes within energy constraints than the 1992 Pyramid.

    PubMed

    Gao, Xiang; Wilde, Parke E; Lichtenstein, Alice H; Tucker, Katherine L

    2006-05-01

    The USDA issued the Food Guide Pyramid (FGP) to help Americans choose healthy diets. We examined whether adherence to the 1992 and 2005 FGP was associated with moderate energy and adequate nutrient intakes. We used data for 2138 men and 2213 women > 18 y old, from the 2001-2002 U.S. National Health and Nutrition Examination Survey (NHANES). Quadratic programming was used to generate diets with minimal departure from intakes reported for the NHANES 2001-02. We examined the effect of the number of servings/d of Food Pyramid groups set at 1992 and at 2005 FGP recommendations for 1600, 2200, and 2800 kcal (1 kcal = 4.184 kJ) levels. We calculated energy and nutrients provided by different FGP dietary patterns. Within current U.S. dietary practices, following the 1992 FGP without sodium restriction may provide 200 more kcal than recommended for each energy level. Although it can meet most of old nutrient recommendations (1989), it fails to meet the latest dietary reference intakes, especially for the 1600 kcal level. The 2005 FGP appears to provide less energy and more adequate nutrient intakes, with the exception of vitamin E and potassium for some groups. However, without discretionary energy restriction, Americans are at risk of having excessive energy intake even if they follow the 2005 FGP food serving recommendations. Our analysis suggests that following the 2005 FGP may be associated with lower energy and optimal nutrient intake. Careful restriction of discretionary calories appears necessary for appropriate energy intakes to be maintained.

  9. Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores

    PubMed Central

    Moreira, X; Zas, R; Sampedro, L

    2013-01-01

    The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future. PMID:23232833

  10. Additive genetic variation in resistance traits of an exotic pine species: little evidence for constraints on evolution of resistance against native herbivores.

    PubMed

    Moreira, X; Zas, R; Sampedro, L

    2013-05-01

    The apparent failure of invasions by alien pines in Europe has been explained by the co-occurrence of native pine congeners supporting herbivores that might easily recognize the new plants as hosts. Previous studies have reported that exotic pines show reduced tolerance and capacity to induce resistance to those native herbivores. We hypothesize that limited genetic variation in resistance to native herbivores and the existence of evolutionary trade-offs between growth and resistance could represent additional potential constraints on the evolution of invasiveness of exotic pines outside their natural range. In this paper, we examined genetic variation for constitutive and induced chemical defences (measured as non-volatile resin in the stem and total phenolics in the needles) and resistance to two major native generalist herbivores of pines in cafeteria bioassays (the phloem-feeder Hylobius abietis and the defoliator Thaumetopoea pityocampa) using half-sib families drawn from a sample of the population of Pinus radiata introduced to Spain in the mid-19th century. We found (i) significant genetic variation, with moderate-to-high narrow-sense heritabilities for both the production of constitutive non-volatile resin and induced total phenolics, and for constitutive resistance against T. pityocampa in bioassays, (ii) no evolutionary trade-offs between plant resistance and growth traits or between the production of different quantitative chemical defences and (iii) a positive genetic correlation between constitutive resistance to the two studied herbivores. Overall, results of our study indicate that the exotic pine P. radiata has limited genetic constraints on the evolution of resistance against herbivores in its introduced range, suggesting that, at least in terms of interactions with these enemies, this pine species has potential to become invasive in the future.

  11. Guided macro-mutation in a graded energy based genetic algorithm for protein structure prediction.

    PubMed

    Rashid, Mahmood A; Iqbal, Sumaiya; Khatib, Firas; Hoque, Md Tamjidul; Sattar, Abdul

    2016-04-01

    Protein structure prediction is considered as one of the most challenging and computationally intractable combinatorial problem. Thus, the efficient modeling of convoluted search space, the clever use of energy functions, and more importantly, the use of effective sampling algorithms become crucial to address this problem. For protein structure modeling, an off-lattice model provides limited scopes to exercise and evaluate the algorithmic developments due to its astronomically large set of data-points. In contrast, an on-lattice model widens the scopes and permits studying the relatively larger proteins because of its finite set of data-points. In this work, we took the full advantage of an on-lattice model by using a face-centered-cube lattice that has the highest packing density with the maximum degree of freedom. We proposed a graded energy-strategically mixes the Miyazawa-Jernigan (MJ) energy with the hydrophobic-polar (HP) energy-based genetic algorithm (GA) for conformational search. In our application, we introduced a 2 × 2 HP energy guided macro-mutation operator within the GA to explore the best possible local changes exhaustively. Conversely, the 20 × 20 MJ energy model-the ultimate objective function of our GA that needs to be minimized-considers the impacts amongst the 20 different amino acids and allow searching the globally acceptable conformations. On a set of benchmark proteins, our proposed approach outperformed state-of-the-art approaches in terms of the free energy levels and the root-mean-square deviations.

  12. Specific immunotherapy of experimental myasthenia by genetically engineered APCs: the "guided missile" strategy.

    PubMed

    Drachman, D B; Wu, J-M; Miagkov, A; Williams, M A; Adams, R N; Wu, B

    2003-09-01

    Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell-dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR-specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen-presenting cells (APCs) to "guided missiles" that target AChR-specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen-specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a "warhead" of Fas ligand (FasL) to eliminate the activated AChR-specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR-specific T cells by the Fas/FasL pathway, while sparing T cells of other specificities.

  13. Pre-Clinical Drug Prioritization via Prognosis-Guided Genetic Interaction Networks

    PubMed Central

    Xiong, Jianghui; Liu, Juan; Rayner, Simon; Tian, Ze; Li, Yinghui; Chen, Shanguang

    2010-01-01

    The high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Patient population heterogeneity and unpredictable physiology complicate pre-clinical cancer modeling efforts. We hypothesize that gene networks associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. Here we propose a novel in vivo genetic interaction which we call ‘synergistic outcome determination’ (SOD), a concept similar to ‘Synthetic Lethality’. SOD is defined as the synergy of a gene pair with respect to cancer patients' outcome, whose correlation with outcome is due to cooperative, rather than independent, contributions of genes. The method combines microarray gene expression data with cancer prognostic information to identify synergistic gene-gene interactions that are then used to construct interaction networks based on gene modules (a group of genes which share similar function). In this way, we identified a cluster of important epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to the cancer-specific inter-module network, we defined a perturbation index for each drug based upon its characteristic perturbation pattern on the inter-module network. Finally, by calculating this index for compounds in the NCI Standard Agent Database, we significantly discriminated successful drugs from a broad set of test compounds, and further revealed the mechanisms of drug combinations. Thus, prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies. PMID:21085674

  14. Low genetic diversity and functional constraint in loci encoding Plasmodium vivax P12 and P38 proteins in the Colombian population.

    PubMed

    Forero-Rodríguez, Johanna; Garzón-Ospina, Diego; Patarroyo, Manuel A

    2014-02-18

    Plasmodium vivax is one of the five species causing malaria in human beings, affecting around 391 million people annually. The development of an anti-malarial vaccine has been proposed as an alternative for controlling this disease. However, its development has been hampered by allele-specific responses produced by the high genetic diversity shown by some parasite antigens. Evaluating these antigens' genetic diversity is thus essential when designing a completely effective vaccine. The gene sequences of Plasmodium vivax p12 (pv12) and p38 (pv38), obtained from field isolates in Colombia, were used for evaluating haplotype polymorphism and distribution by population genetics analysis. The evolutionary forces generating the variation pattern so observed were also determined. Both pv12 and pv38 were shown to have low genetic diversity. The neutral model for pv12 could not be discarded, whilst polymorphism in pv38 was maintained by balanced selection restricted to the gene's 5' region. Both encoded proteins seemed to have functional/structural constraints due to the presence of s48/45 domains, which were seen to be highly conserved. Due to the role that malaria parasite P12 and P38 proteins seem to play during invasion in Plasmodium species, added to the Pv12 and Pv38 antigenic characteristics and the low genetic diversity observed, these proteins might be good candidates to be evaluated in the design of a multistage/multi-antigen vaccine.

  15. Three-dimensional prostate segmentation using level set with shape constraint based on rotational slices for 3D end-firing TRUS guided biopsy.

    PubMed

    Qiu, Wu; Yuan, Jing; Ukwatta, Eranga; Tessier, David; Fenster, Aaron

    2013-07-01

    Prostate segmentation is an important step in the planning and treatment of 3D end-firing transrectal ultrasound (TRUS) guided prostate biopsy. In order to improve the accuracy and efficiency of prostate segmentation in 3D TRUS images, an improved level set method is incorporated into a rotational-slice-based 3D prostate segmentation to decrease the accumulated segmentation errors produced by the slice-by-slice segmentation method. A 3D image is first resliced into 2D slices in a rotational manner in both the clockwise and counterclockwise directions. All slices intersect approximately along the rotational scanning axis and have an equal angular spacing. Six to eight boundary points are selected to initialize a level set function to extract the prostate contour within the first slice. The segmented contour is then propagated to the adjacent slice and is used as the initial contour for segmentation. This process is repeated until all slices are segmented. A modified distance regularization level set method is used to segment the prostate in all resliced 2D slices. In addition, shape-constraint and local-region-based energies are imposed to discourage the evolved level set function to leak in regions with weak edges or without edges. An anchor point based energy is used to promote the level set function to pass through the initial selected boundary points. The algorithm's performance was evaluated using distance- and volume-based metrics (sensitivity (Se), Dice similarity coefficient (DSC), mean absolute surface distance (MAD), maximum absolute surface distance (MAXD), and volume difference) by comparison with expert delineations. The validation results using thirty 3D patient images showed that the authors' method can obtain a DSC of 93.1% ± 1.6%, a sensitivity of 93.0% ± 2.0%, a MAD of 1.18 ± 0.36 mm, a MAXD of 3.44 ± 0.8 mm, and a volume difference of 2.6 ± 1.9 cm(3) for the entire prostate. A reproducibility experiment demonstrated that the proposed method

  16. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  17. Development of a Tool to Guide Parents Carrying a BRCA1/2 Mutation Share Genetic Results with Underage Children.

    PubMed

    Santerre-Theil, Ariane; Bouchard, Karine; St-Pierre, Dominique; Drolet, Anne-Marie; Chiquette, Jocelyne; Dorval, Michel

    2016-11-02

    Although most parents carrying a BRCA1/2 genetic mutation share their test result with their underage children, they report needing support to decide if, when, and how to share risk information and what reactions to expect from their children. We developed a tool to guide parents carrying a BRCA1/2 mutation share their genetic result with underage children. Here, we report on the development of this tool using a qualitative methodology. A tool prototype was developed based on the International Patient Decision Aids Standards Collaboration framework. Content was assessed using feedback from focus groups, individual interviews, and a 12-item reading grid. Participants were nine BRCA1/2 mutation carriers with underage children and three cancer genetics health professionals. Thematic content analysis was conducted on interview transcripts. The tool was developed using an iterative process until saturation of data. An independent advisory committee was involved in all steps of tool development until reaching consensus. Rather than a decision aid per se (to communicate or not), the parents wanted a more comprehensive tool to help them communicate genetic test result to their children. To meet parents' needs, a communication guidance booklet was developed, setting out the pros and cons of communication, steps to prepare sharing the test result, communication tips, and parents' testimonies. This communication tool responds to a significant unmet need faced by parents carrying a genetic predisposition to cancer. Future studies are needed to assess how the information from the parent's genetic test result impacts the child's development, health behaviors, and relationship with the parent.

  18. Developing a systematic strategy incorporating ethical , animal welfare and practice principles to guide the genetic improvement of dairy cattle.

    PubMed

    Fisher, M W; Mellor, D J

    2008-06-01

    People have complex and diverse relationships and interactions with, and expectations of, animals; relationships which are very important. In making sense of this complexity, we draw on our values. The objective of this study was to reflect upon, develop and articulate key values guiding the genetic improvement of dairy cattle. Animal husbandry is guided by the philosophy that while animals serve our needs, we must ensure that their needs are met, and any compromises to those needs justified and minimised. In applying modern technology to the genetic improvement of animals, this philosophy should be enacted through consideration of all the broader goals of agriculture, and the ecology and biology of the farming system. It should also be informed by the differing perspectives of interested parties, including stock handlers, veterinarians, animal welfare groups, consumers, and the public. Monitoring the consequences of technology applications, managing and avoiding any harms, and considering the future of animals and ourselves, should also be part of decision making in this area. Transparent consideration of these principles will help to ensure that any compromises to animal welfare resulting from trait selection are both reasonable and necessary, and that any harms are minimised, thereby helping to safeguard continuation of the important contribution that animal agriculture, and in particular the dairy sector, makes to society.

  19. AudioGene: Predicting Hearing Loss Genotypes from Phenotypes to Guide Genetic Screening

    PubMed Central

    Taylor, Kyle R.; DeLuca, Adam P.; Shearer, A. Eliot; Hildebrand, Michael S.; Black-Ziegelbein, E. Ann; Anand, V. Nikhil; Sloan, Christina M.; Eppsteiner, Robert W.; Scheetz, Todd E.; Huygen, Patrick L. M.; Smith, Richard J. H.; Braun, Terry A.; Casavant, Thomas L.

    2013-01-01

    Autosomal Dominant Nonsyndromic Hearing Loss (ADNSHL) is a common and often progressive sensory deficit. ADNSHL displays a high degree of genetic heterogeneity, and varying rates of progression. Accurate, comprehensive and cost-effective genetic testing facilitates genetic counseling and provides valuable prognostic information to affected individuals. In this paper, we describe the algorithm underlying AudioGene, a software system employing machine-learning techniques that utilizes phenotypic information derived from audiograms to predict the genetic cause of hearing loss in persons segregating ADNSHL. Our data show that AudioGene has an accuracy of 68% in predicting the causative gene within its top three predictions, as compared to 44% for a Majority classifier. We also show that AudioGene remains effective for audiograms with high levels of clinical measurement noise. We identify audiometric outliers for each genetic locus and hypothesize that outliers may reflect modifying genetic effects. As personalized genomic medicine becomes more common, AudioGene will be increasingly useful as a phenotypic filter to assess pathogenicity of variants identified by massively parallel sequencing. PMID:23280582

  20. Clinical Value of CYP2C19 Genetic Testing for Guiding the Antiplatelet Therapy in a Chinese Population.

    PubMed

    Shen, De-Liang; Wang, Bo; Bai, Jing; Han, Qing; Liu, Chuang; Huang, Xiao-Hui; Zhang, Jin-Ying

    2016-03-01

    To compare the clinical effects between individual antiplatelet therapy guided by CYP2C19 genetic testing and conventional dual antiplatelet therapy in patients with coronary artery disease after percutaneous coronary intervention. In total of 628 coronary artery disease patients who had undergone successful percutaneous coronary intervention were included in this study. Patients were consecutively divided into routine group (n = 319) and individual group (n = 309) because of weather received CYP2C19 genetic testing. The individual group was divided again into extensive metabolizer group, intermediate metabolizer group, and poor metabolizer group according to CYP2C19 genotype. Then extensive metabolizer group received 75 mg daily of clopidogrel, intermediate metabolizer group received 150 mg daily of clopidogrel, and poor metabolizer group received ticagrelor 90 mg twice daily. Routine group was treated with clopidogrel 75 mg daily conventionally. The primary end points were defined as major adverse cardiovascular events (MACE), namely a composite of death from any cause, myocardial infarction, or target vessel revascularization. Safety end points were bleeding events classified by GUSTO. All the 628 patients were followed for an average of 12 months and clinical outcomes were analyzed at 1, 6, and 12 months after discharge. The morbidity rates of MACE in individual group were all lower than those in routine group at 1, 6, and 12 months (1.3% vs. 5.6%, P = 0.003; 3.2% vs. 7.8%, P = 0.012; 4.2% vs. 9.4%, P = 0.010). No significant difference in the rates of bleeding was found between the 2 groups (P > 0.05). Even performed a multivariate logistic regression analysis, the benefit of individual antiplatelet therapy remained. Individual antiplatelet therapy guided by CYP2C19 genetic testing significantly reduced the rate of MACE without an increase in the rate of bleeding in the near term in this Chinese population.

  1. The Use of Genetic Algorithms as an Inverse Technique to Guide the Design and Implementation of Research at a Test Site in Shelby County, Tennessee

    NASA Astrophysics Data System (ADS)

    Gentry, R. W.

    2002-12-01

    The Shelby Farms test site in Shelby County, Tennessee is being developed to better understand recharge hydraulics to the Memphis aquifer in areas where leakage through an overlying aquitard occurs. The site is unique in that it demonstrates many opportunities for interdisciplinary research regarding environmental tracers, anthropogenic impacts and inverse modeling. The objective of the research funding the development of the test site is to better understand the groundwater hydrology and hydraulics between a shallow alluvial aquifer and the Memphis aquifer given an area of leakage, defined as an aquitard window. The site is situated in an area on the boundary of a highly developed urban area and is currently being used by an agricultural research agency and a local recreational park authority. Also, an abandoned landfill is situated to the immediate south of the window location. Previous research by the USGS determined the location of the aquitard window subsequent to the landfill closure. Inverse modeling using a genetic algorithm approach has identified the likely extents of the area of the window given an interaquifer accretion rate. These results, coupled with additional fieldwork, have been used to guide the direction of the field studies and the overall design of the research project. This additional work has encompassed the drilling of additional monitoring wells in nested groups by rotasonic drilling methods. The core collected during the drilling will provide additional constraints to the physics of the problem that may provide additional help in redefining the conceptual model. The problem is non-unique with respect to the leakage area and accretion rate and further research is being performed to provide some idea of the advective flow paths using a combination of tritium and 3He analyses and geochemistry. The outcomes of the research will result in a set of benchmark data and physical infrastructure that can be used to evaluate other environmental

  2. Understanding genetic risk for substance use and addiction: a guide for non-geneticists.

    PubMed

    Urbanoski, Karen A; Kelly, John F

    2012-02-01

    There is considerable enthusiasm for the potential of genetics research for prevention and treatment of addiction and other mental disorders. As a result, clinicians are increasingly exposed to issues of genetics that are fairly complex, and for which they may not have been adequately prepared by their training. Studies suggest that the heritability of substance use disorders is approximately 0.5. Others report that family members of affected individuals experience a 4- to 8-fold increased risk of disorder themselves. Statements that addiction is "50% genetic" in origin may be taken by some to imply one's chances of developing the disorder, or that a lack of a positive family history confers immunity. In fact, such conclusions are inaccurate, their implications unwarranted given the true meaning of heritability. Through a review of basic concepts in genetic epidemiology, we attempt to demystify these estimates of risk and situate them within the broader context of addiction. Methods of inferring population genetic variance and individual familial risk are examined, with a focus on their practical application and limitations. An accurate conceptualization of addiction necessitates an approach that transcends specific disciplines, making a basic awareness of the perspectives of disparate specialties key to furthering progress in the field.

  3. The genetics of Autism Spectrum Disorders--a guide for clinicians.

    PubMed

    Heil, Karsten M; Schaaf, Christian P

    2013-01-01

    Recent advances in genetic testing technology have made chromosome microarray analysis (CMA) a first-tier clinical diagnostic test for Autism Spectrum Disorders (ASDs). Two main types of microarrays are available, single nucleotide polymorphism (SNP) arrays and array comparative genomic hybridization (aCGH), each with its own advantages and disadvantages in ASDs testing. Rare genetic variants, and copy number variants (CNVs) in particular, have been shown to play a major role in ASDs. More than 200 autism susceptibility genes have been identified to date, and complex patterns of inheritance, such as oligogenic heterozygosity, appear to contribute to the etiopathogenesis of ASDs. Incomplete penetrance and variable expressivity represent particular challenges in the interpretation of CMA testing of autistic individuals. This review aims to provide an overview of autism genetics for the practicing physician and gives hands-on advice on how to follow-up on abnormal CMA findings in individuals with neuropsychiatric disorders.

  4. Advances in the Genetics of Congenital Heart Disease: A Clinician's Guide.

    PubMed

    Blue, Gillian M; Kirk, Edwin P; Giannoulatou, Eleni; Sholler, Gary F; Dunwoodie, Sally L; Harvey, Richard P; Winlaw, David S

    2017-02-21

    Our understanding of the genetics of congenital heart disease (CHD) is rapidly expanding; however, many questions, particularly those relating to sporadic forms of disease, remain unanswered. Massively parallel sequencing technology has made significant contributions to the field, both from a diagnostic perspective for patients and, importantly, also from the perspective of disease mechanism. The importance of de novo variation in sporadic disease is a recent highlight, and the genetic link between heart and brain development has been established. Furthermore, evidence of an underlying burden of genetic variation contributing to sporadic and familial forms of CHD has been identified. Although we are still unable to identify the cause of CHD for most patients, recent findings have provided us with a much clearer understanding of the types of variants and their individual contributions and collectively mark an important milestone in our understanding of both familial and sporadic forms of disease.

  5. Implementing Algorithm-Guided Warfarin Dosing in an Ethnically Diverse Patient Population Using Electronic Health Records and Preemptive CYP2C9 and VKORC1 Genetic Testing.

    PubMed

    Obeng, A Owusu; Kaszemacher, T; Abul-Husn, N S; Gottesman, O; Vega, A; Waite, E; Myers, K; Cho, J; Bottinger, E P; Ellis, S B; Scott, S A

    2016-11-01

    Implementation of pharmacogenetic-guided warfarin dosing has been hindered by inconsistent results from reported clinical trials and a lack of available algorithms that include alleles prevalent in non-white populations. However, current evidence indicates that algorithm-guided dosing is more accurate than empirical dosing. To facilitate multiethnic algorithm-guided warfarin dosing using preemptive genetic testing, we developed a strategy that accounts for the complexity of race and leverages electronic health records for algorithm variables and deploying point-of-care dose recommendations. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  6. Simulation of Finnish Population History, Guided by Empirical Genetic Data, to Assess Power of Rare-Variant Tests in Finland

    PubMed Central

    Wang, Sophie R.; Agarwala, Vineeta; Flannick, Jason; Chiang, Charleston W.K.; Altshuler, David; Flannick, Jason; Manning, Alisa; Hartl, Christopher; Agarwala, Vineeta; Fontanillas, Pierre; Green, Todd; Banks, Eric; DePristo, Mark; Poplin, Ryan; Shakir, Khalid; Fennell, Timothy; Murphy, Jacquelyn; Burtt, Noël; Gabriel, Stacey; Altshuler, David; Fuchsberger, Christian; Kang, Hyun Min; Sim, Xueling; Ma, Clement; Locke, Adam; Blackwell, Thomas; Jackson, Anne; Teslovich, Tanya; Stringham, Heather; Chines, Peter; Kwan, Phoenix; Huyghe, Jeroen; Tan, Adrian; Jun, Goo; Stitzel, Michael; Bergman, Richard N.; Bonnycastle, Lori; Tuomilehto, Jaakko; Collins, Francis S.; Scott, Laura; Mohlke, Karen; Abecasis, Gonçalo; Boehnke, Michael; Strom, Tim; Gieger, Christian; Müller-Nurasyid, Martina; Grallert, Harald; Kriebel, Jennifer; Ried, Janina; Hrabé de Angelis, Martin; Huth, Cornelia; Meisinger, Christa; Peters, Annette; Rathmann, Wolfgang; Strauch, Konstantin; Meitinger, Thomas; Kravic, Jasmina; Ladenvall, Claes; Toumi, Tiinamaija; Isomaa, Bo; Groop, Leif; Gaulton, Kyle; Moutsianas, Loukas; Rivas, Manny; Pearson, Richard; Mahajan, Anubha; Prokopenko, Inga; Kumar, Ashish; Perry, John; Chen, Jeff; Howie, Bryan; van de Bunt, Martijn; Small, Kerrin; Lindgren, Cecilia; Lunter, Gerton; Robertson, Neil; Rayner, Will; Morris, Andrew; Buck, David; Hattersley, Andrew; Spector, Tim; McVean, Gil; Frayling, Tim; Donnelly, Peter; McCarthy, Mark; Hirschhorn, Joel N.

    2014-01-01

    Finnish samples have been extensively utilized in studying single-gene disorders, where the founder effect has clearly aided in discovery, and more recently in genome-wide association studies of complex traits, where the founder effect has had less obvious impacts. As the field starts to explore rare variants’ contribution to polygenic traits, it is of great importance to characterize and confirm the Finnish founder effect in sequencing data and to assess its implications for rare-variant association studies. Here, we employ forward simulation, guided by empirical deep resequencing data, to model the genetic architecture of quantitative polygenic traits in both the general European and the Finnish populations simultaneously. We demonstrate that power of rare-variant association tests is higher in the Finnish population, especially when variants’ phenotypic effects are tightly coupled with fitness effects and therefore reflect a greater contribution of rarer variants. SKAT-O, variable-threshold tests, and single-variant tests are more powerful than other rare-variant methods in the Finnish population across a range of genetic models. We also compare the relative power and efficiency of exome array genotyping to those of high-coverage exome sequencing. At a fixed cost, less expensive genotyping strategies have far greater power than sequencing; in a fixed number of samples, however, genotyping arrays miss a substantial portion of genetic signals detected in sequencing, even in the Finnish founder population. As genetic studies probe sequence variation at greater depth in more diverse populations, our simulation approach provides a framework for evaluating various study designs for gene discovery. PMID:24768551

  7. Inter- and intrapopulation variation in thermal reaction norms for growth rate: evolution of latitudinal compensation in ectotherms with a genetic constraint.

    PubMed

    Yamahira, Kazunori; Kawajiri, Maiko; Takeshi, Kenichi; Irie, Takahiro

    2007-07-01

    In ectotherms, lower temperatures in high-latitude environments would theoretically reduce the annual growth rates of individuals. If slower growth and resultant smaller body size reduce fitness, individuals in higher latitudes may evolve compensatory responses. Two alternative models of such latitudinal compensation are possible: Model I: thermal reaction norms for growth rates of high-latitude individuals may be horizontally shifted to a lower range of temperatures, or Model II: reaction norms may be vertically shifted so that high-latitude individuals can grow faster across all temperatures. Model I is expected when annual growth rates in the wild are only a function of environmental temperatures, whereas Model II is expected when individuals in higher latitudes can only grow during a shorter period of a year. A variety of mixed strategies of these two models are also possible, and the magnitude of horizontal versus vertical variation in reaction norms among latitudinal populations will be indicative of the importance of "temperature" versus "seasonality" in the evolution of latitudinal compensation. However, the form of latitudinal compensation may be affected by possible genetic constraints due to the genetic architecture of reaction norms. In this study, we examine the inter- and intrapopulation variations in thermal reaction norms for growth rate of the medaka fish Oryzias latipes. Common-environment experiments revealed that average reaction norms differed primarily in elevation among latitudinal populations in a manner consistent with Model II (adaptation to "seasonality"), suggesting that natural selection in high latitudes prefers individuals that grow faster even within a shorter growing season to individuals that have longer growing seasons by growing at lower temperatures. However, intrapopulation variation in reaction norms was also vertical: some full-sibling families grew faster than others across all temperatures examined. This tendency in

  8. Landscape genetic approaches to guide native plant restoration in the Mojave Desert

    USGS Publications Warehouse

    Shryock, Daniel F.; Havrilla, Caroline A.; DeFalco, Lesley; Esque, Todd C.; Custer, Nathan; Wood, Troy E.

    2016-01-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially-explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  9. Landscape genetic approaches to guide native plant restoration in the Mojave Desert.

    PubMed

    Shryock, Daniel F; Havrilla, Caroline A; DeFalco, Lesley A; Esque, Todd C; Custer, Nathan A; Wood, Troy E

    2017-03-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  10. Quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design.

    PubMed

    Smith, Justin D; Suresh, Sundari; Schlecht, Ulrich; Wu, Manhong; Wagih, Omar; Peltz, Gary; Davis, Ronald W; Steinmetz, Lars M; Parts, Leopold; St Onge, Robert P

    2016-03-08

    Genome-scale CRISPR interference (CRISPRi) has been used in human cell lines; however, the features of effective guide RNAs (gRNAs) in different organisms have not been well characterized. Here, we define rules that determine gRNA effectiveness for transcriptional repression in Saccharomyces cerevisiae. We create an inducible single plasmid CRISPRi system for gene repression in yeast, and use it to analyze fitness effects of gRNAs under 18 small molecule treatments. Our approach correctly identifies previously described chemical-genetic interactions, as well as a new mechanism of suppressing fluconazole toxicity by repression of the ERG25 gene. Assessment of multiple target loci across treatments using gRNA libraries allows us to determine generalizable features associated with gRNA efficacy. Guides that target regions with low nucleosome occupancy and high chromatin accessibility are clearly more effective. We also find that the best region to target gRNAs is between the transcription start site (TSS) and 200 bp upstream of the TSS. Finally, unlike nuclease-proficient Cas9 in human cells, the specificity of truncated gRNAs (18 nt of complementarity to the target) is not clearly superior to full-length gRNAs (20 nt of complementarity), as truncated gRNAs are generally less potent against both mismatched and perfectly matched targets. Our results establish a powerful functional and chemical genomics screening method and provide guidelines for designing effective gRNAs, which consider chromatin state and position relative to the target gene TSS. These findings will enable effective library design and genome-wide programmable gene repression in many genetic backgrounds.

  11. RNA-Guided Cas9-Induced Mutagenesis in Tobacco Followed by Efficient Genetic Fixation in Doubled Haploid Plants

    PubMed Central

    Schedel, Sindy; Pencs, Stefanie; Hensel, Götz; Müller, Andrea; Rutten, Twan; Kumlehn, Jochen

    2017-01-01

    Customizable endonucleases are providing an effective tool for genome engineering. The resulting primary transgenic individuals (T0) are typically heterozygous and/or chimeric with respect to any mutations induced. To generate genetically fixed mutants, they are conventionally allowed to self-pollinate, a procedure which segregates individuals into mutant heterozygotes/homozygotes and wild types. The chances of recovering homozygous mutants among the progeny depend not only on meiotic segregation but also on the frequency of mutated germline cells in the chimeric mother plant. In Nicotiana species, the heritability of Cas9-induced mutations has not been demonstrated yet. RNA-guided Cas9 endonuclease-mediated mutagenesis was targeted to the green fluorescent protein (GFP) gene harbored by a transgenic tobacco line. Upon retransformation using a GFP-specific guide RNA/Cas9 construct, the T0 plants were allowed to either self-pollinate, or were propagated via regeneration from in vitro cultured embryogenic pollen which give rise to haploid/doubled haploid plants or from leaf explants that form plants vegetatively. Single or multiple mutations were detected in 80% of the T0 plants. About half of these mutations proved heritable via selfing. Regeneration from in vitro cultured embryogenic pollen allowed for homozygous mutants to be produced more efficiently than via sexual reproduction. Consequently, embryogenic pollen culture provides a convenient method to rapidly generate a variety of genetically fixed mutants following site-directed mutagenesis. The recovery of a mutation not found among sexually produced and analyzed progeny was shown to be achievable through vegetative plant propagation in vitro, which eventually resulted in heritability when the somatic clones were selfed. In addition, some in-frame mutations were associated with functional attenuation of the target gene rather than its full knock-out. The generation of mutants with compromised rather than

  12. Clinical application of genetics to guide prevention and treatment of oral diseases

    PubMed Central

    Kornman, KS; Polverini, PJ

    2014-01-01

    Dental care costs in the United States exceed $100 billion annually. Personalized medicine efforts in dentistry are driven by potentially compelling clinical utility and cost-effectiveness prospects in the major diseases of periodontitis, caries, and oral cancers. This review discusses progress and challenges identifying genetic markers and showing clinical utility in dentistry. Genome-wide association studies (GWAS) of chronic periodontitis (CP) identified no significant variants, but CDKN2BAS variants on chromosome 9 were significantly associated with aggressive periodontitis. Stratifying patients by interleukin (IL)-1 gene variants, smoking and diabetes differentiated CP prevention outcomes. Dental caries’ GWAS identified significant signals in LYZL2, AJAp1, and KPNA4; and efforts are ongoing to identify genetic factors for multiple caries phenotypes. Trials of molecularly targeted therapies are in progress for oral, head, and neck squamous cell carcinomas (OHNSCC) and results have been promising but limited in their effectiveness. Current opportunities and challenges for molecular targeting for OHNSCC are discussed. PMID:24702466

  13. Genetic algorithm-guided discovery of additive combinations that direct quantum dot assembly.

    PubMed

    Bawazer, Lukmaan A; Ihli, Johannes; Comyn, Timothy P; Critchley, Kevin; Empson, Christopher J; Meldrum, Fiona C

    2015-01-14

    The use of combinations of organic additives to control crystallization, as occurs in biomineralization, is rarely investigated due to the vast potential reaction space. It is demonstrated here that combinatorial approaches led by genetic algorithm heuristics can enable identification of active additive combinations, and four key organic molecules are rapidly identified, which generate highly fluorescent CdS quantum dot superstructures. © 2014 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Genetics of inflammasome-associated disorders: a lesson in the guiding principals of inflammasome function.

    PubMed

    Rodrigue-Gervais, Ian Gaël; Saleh, Maya

    2010-03-01

    Human genetics research has had a great impact on the genesis of the inflammasome field and the treatment of certain inflammasomopathies. The identification of mutations causing rare autoinflammatory syndromes, reproductive wastage disorders and of single nucleotide polymorphisms influencing susceptibility to complex diseases such as vitiligo, sepsis, and Crohn's disease has not only led to the characterization of novel proteins involved in NOD-like receptor-coupled inflammatory signaling pathways but also to greater insights into pathogenic mechanisms.

  15. Geomorphic and Fish Genetics Constraints on Late Cenozoic Long Wavelength Topographic Evolution of the Hangay Mountains, Central Mongolia

    NASA Astrophysics Data System (ADS)

    Wegmann, K. W.; Tamra, M.; Sabaj Pérez, M.; Lopresti, M.; Cole, M. B.; Gosse, J. C.; Smith, S. G.; Bayasgalan, G.; Ancuta, L. D.; McDannell, K. T.; Gallen, S. F.

    2014-12-01

    The Hangay Mountains stand 1.5 - 2 km above adjacent lowlands and the timing and cause of their high elevation is debated. As part of a broad collaborative project, we synthesize several data sets that collectively suggest the Hangay increased in elevation during the mid-to-late Miocene, while topographic relief, one metric commonly associated with active mountain ranges, remained largely unchanged. The topographic crest of the Hangay forms the drainage divide between the Selenga River and internal drainage of the Mongolian Depression of Lakes (MDL) and northern Gobi. Synthetic drainage divides for the Hangay were created by filtering digital topography in the spectral domain (50 - 200 km wavelengths) using a 2D-FFT function. The co-location of the synthetic and modern divides suggests that the Hangay divide is in a stable, equilibrium configuration. This assumption is corroborated by chi-maps of steady-state river channel elevations that exhibit nearly equal values across water divides. An exception to both of these metrics occurs in the northwest Hangay where the Bulnay fault crosses a low divide between the western Selenga basin and the MDL. Recent basalt vesicle paleoaltimetry results allow for ~1 km of surface uplift of the central Hangay in the past ~ 10 Ma. These same basalt flows in-filled late Miocene valleys cut into basement with a minimum of 800 m of local relief; similar to the amount of modern, post-glacial relief along the drainage divide. mtDNA analyses from > 250 combined Stone Loaches (Barbatula), Grayling (Thymallus), and Eurasian Dace (Leuciscus) samples from both sides of the continental drainage divide are supportive of Miocene surface uplift. Molecular genetic differences between the loach populations across the divide suggest that they separated from a common ancestor between 20 and 11 Ma. This date is consistent with the timing of surface uplift and valley incision preserved in the Miocene basalt flows. The dace and grayling populations on

  16. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  17. Low genetic diversity and functional constraint of miRNA genes participating pollen-pistil interaction in rice.

    PubMed

    Wang, Kun; Wang, Xin; Li, Ming; Shi, Tao; Yang, Pingfang

    2017-07-22

    In this study, we sequenced and analyzed the expression and evolution of rice miRNA genes participating pollen-pistil interaction that is crucial to rice yield. Pollen-pistil interaction is an essential reproductive process for all flowering plants. While microRNAs (miRNAs) are important noncoding small RNAs that regulate mRNA levels in eukaryotic cells, there is little knowledge about which miRNAs involved in the early stages of pollen-pistil interaction in rice and how they evolve under this conserved process. In this study, we sequenced the small RNAs in rice from unpollinated pistil (R0), pistil from 5 min and 15 min after pollination, respectively, to identify known and novel miRNAs that are involved in this process. By comparing the corresponding mRNA-seq dataset, we identified a group of miRNAs with strong negative expression pattern with their target genes. Further investigation of all miRNA loci (MIRNAs) across 1083 public rice accessions revealed significantly reduced genetic diversity in MIRNAs with strong negative expression of their targets when comparing to those with little or no impact on targets during pollen-pistil interaction. Annotation of targets suggested that those MIRNAs with strong impact on targets were pronounced in cell wall related processes such as xylan metabolism. Additionally, plant conserved miRNAs, such as those with functions in gibberellic acid, auxin and nitrate signaling, were also with strong negative expression of their targets. Overall, our analyses identified key miRNAs participating pollen-pistil interaction and their evolutionary patterns in rice, which can facilitate the understanding of molecular mechanisms associated with seed setting.

  18. Lost in the space of bioinformatic tools: a constantly updated survival guide for genetic epidemiology. The GenEpi Toolbox.

    PubMed

    Coassin, Stefan; Brandstätter, Anita; Kronenberg, Florian

    2010-04-01

    Genome-wide association studies (GWASs) led to impressive advances in the elucidation of genetic factors underlying complex phenotypes and diseases. However, the ability of GWAS to identify new susceptibility loci in a hypothesis-free approach requires tools to quickly retrieve comprehensive information about a genomic region and analyze the potential effects of coding and non-coding SNPs in a candidate gene region. Furthermore, once a candidate region is chosen for resequencing and fine-mapping studies, the identification of several rare mutations is likely and requires strong bioinformatic support to properly evaluate and prioritize the found mutations for further analysis. Due to the variety of regulatory layers that can be affected by a mutation, a comprehensive in-silico evaluation of candidate SNPs can be a demanding and very time-consuming task. Although many bioinformatic tools that significantly simplify this task were made available in the last years, their utility is often still unknown to researches not intensively involved in bioinformatics. We present a comprehensive guide of 64 tools and databases to bioinformatically analyze gene regions of interest to predict SNP effects. In addition, we discuss tools to perform data mining of large genetic regions, predict the presence of regulatory elements, make in-silico evaluations of SNPs effects and address issues ranging from interactome analysis to graphically annotated proteins sequences. Finally, we exemplify the use of these tools by applying them to hits of a recently performed GWAS. Taken together a combination of the discussed tools are summarized and constantly updated in the web-based "GenEpi Toolbox" (http://genepi_toolbox.i-med.ac.at) and can help to get a glimpse at the potential functional relevance of both large genetic regions and single nucleotide mutations which might help to prioritize the next steps.

  19. Identification and Genetic Analysis of Wunen, a Gene Guiding Drosophila Melanogaster Germ Cell Migration

    PubMed Central

    Zhang, N.; Zhang, J.; Cheng, Y.; Howard, K.

    1996-01-01

    We describe a novel genetic locus, wunen (wun), required for guidance of germ cell migration in early Drosophila development. Loss of wun function does not abolish movement but disrupts the orientation of the motion causing the germ cells to disperse even though their normal target, the somatic gonad, is well formed. We demonstrate that the product of this gene enables a signal to pass from the soma to the germ line and propose that the function of this signal is to selectively stabilize certain cytoplasmic extensions resulting in oriented movement. To characterize this guidance factor, we have mapped wun to within 100 kb of cloned DNA. PMID:8807296

  20. Effective Treatment of Aggressive Fibromatosis with Celecoxib Guided by Genetic testing.

    PubMed

    Yang, Shanshan; Wang, Xufu; Jiang, Haiping; Wang, Yongjie; Li, Zhuokun; Lu, Haijun

    2017-09-07

    Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see policy. The use of non-steroidal anti-inflammatory drugs (NSAIDs) and targeted therapies has demonstrated good results. In the case report, a 39-year-old man presented with progressive chest wall pain. Computed tomography (CT) showed an approximately 46 × 13mm soft-tissue mass between the inside of the fifth and sixth rib on the right side. The entire mass was excised and an AF was confirmed based on histopathology. Four months after surgery, magnetic resonance imaging (MRI) showed a soft-tissue mass in surgical areas and biopsy confirmed local recurrence. Therefore, Tomotherapy was administered. However, two months later, an (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography combined with CT (PET-CT) revealed the presence of an FDG-avid mass in the area of local recurrence. Genetic testing reported the presence of a p.T41A mutations on the CTNNB1 gene, which predicted that he is sensitive to the COX-2 inhibitor celecoxib. The tumor regressed rapidly after the application of celecoxib. Within the 20-month follow-up period, the patient showed remarkable regression without any signs and symptoms. Our case report provides further evidence for the efficacy of celecoxib in AF with CTNNB1 gene mutations. To our knowledge, this is the first report of AF treated with celecoxib under the guidance of the genetic testing. However, further studies are required.

  1. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    PubMed Central

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10−9). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10−9), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA–approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  2. The use of genetic epidemiology to guide classification in child and adult psychopathology.

    PubMed

    Szatmari, Peter; White, Julie; Merikangas, Kathleen R

    2007-10-01

    The goal of this paper is to illustrate the application of the tools of genetic epidemiology, particularly the family study method, to inform the classification of psychiatric disorders in adults and children. The first section describes family studies of adults designed to investigate the causes of comorbidity of anxiety and depression. The analysis of familial traits provides stronger evidence for the validity of certain sub-types of anxiety and mood disorders that co-occur within the same individual and within families. The second section presents an example of the use of the family study method to examine the validity of the autism spectrum disorders (ASD). A review of these studies suggests that the most consistently familial traits in ASD are language and communication skills, insistence on sameness and non-verbal IQ. These are also the traits most commonly associated with the differentiation of autism from Asperger disorder and PDDNOS using both cross-sectional and longitudinal studies. From these data, a new classification system of the ASDs is proposed based on these familial traits.

  3. A concise genetic and clinical guide to multiple endocrine neoplasias and related syndromes.

    PubMed

    Stratakis, C A; Ball, D W

    2000-05-01

    Several familial neoplastic syndromes are associated with endocrine gland oncogenesis. The main ones are: multiple endocrine neoplasia type 1 (MEN 1), which affects primarily the pituitary, pancreas, and parathyroid glands; MEN 2A and MEN 2B, which involve mainly the thyroid and parathyroid glands and the adrenal medulla; familial medullary thyroid carcinoma (FMTC), which affects only the thyroid gland; and, finally, Carney complex, which affects the adrenal cortex, pituitary, thyroid gland, and the gonads. Carney complex is also associated with pigmentation abnormalities and myxoid and other neoplasms of mesenchymal origin. Thus, this syndrome also belongs to another group of genetic disorders, those associated with pigmentation defects and multiple tumors, including tumors of the endocrine glands. Peutz-Jeghers syndrome and Cowden disease are just two of these disorders that have recently been elucidated at the molecular level. von Hippel-Lindau disease is another condition that affects the pancreas and adrenal medulla and its gene is also known. The inheritance of the MENs, Carney complex, and related syndromes is autosomal dominant. Clinical recognition of these syndromes at a young age improves clinical outcome and prognosis of the various tumors and decreases associated morbidity and mortality. This review considers a wider, more inclusive view of the MEN syndromes, summarizes their clinical features and presents the newest information on their molecular elucidation.

  4. GIPS: A Software Guide to Sequencing-Based Direct Gene Cloning in Forward Genetics Studies.

    PubMed

    Hu, Han; Wang, Weitao; Zhu, Zhongxu; Zhu, Jianhua; Tan, Deyong; Zhou, Zhipeng; Mao, Chuanzao; Chen, Xin

    2016-04-01

    The Gene Identification via Phenotype Sequencing (GIPS) software considers a range of experimental and analysis choices in sequencing-based forward genetics studies within an integrated probabilistic framework, which enables direct gene cloning from the sequencing of several unrelated mutants of the same phenotype without the need to create segregation populations. GIPS estimates four measurements to help optimize an analysis procedure as follows: (1) the chance of reporting the true phenotype-associated gene; (2) the expected number of random genes that may be reported; (3) the significance of each candidate gene's association with the phenotype; and (4) the significance of violating the Mendelian assumption if no gene is reported or if all candidate genes have failed validation. The usage of GIPS is illustrated with the identification of a rice (Oryza sativa) gene that epistatically suppresses the phenotype of the phosphate2 mutant from sequencing three unrelated ethyl methanesulfonate mutants. GIPS is available at https://github.com/synergy-zju/gips/wiki with the user manual and an analysis example. © 2016 American Society of Plant Biologists. All Rights Reserved.

  5. Orthology Guided Assembly in highly heterozygous crops: creating a reference transcriptome to uncover genetic diversity in Lolium perenne.

    PubMed

    Ruttink, Tom; Sterck, Lieven; Rohde, Antje; Bendixen, Christian; Rouzé, Pierre; Asp, Torben; Van de Peer, Yves; Roldan-Ruiz, Isabel

    2013-06-01

    Despite current advances in next-generation sequencing data analysis procedures, de novo assembly of a reference sequence required for SNP discovery and expression analysis is still a major challenge in genetically uncharacterized, highly heterozygous species. High levels of polymorphism inherent to outbreeding crop species hamper De Bruijn Graph-based de novo assembly algorithms, causing transcript fragmentation and the redundant assembly of allelic contigs. If multiple genotypes are sequenced to study genetic diversity, primary de novo assembly is best performed per genotype to limit the level of polymorphism and avoid transcript fragmentation. Here, we propose an Orthology Guided Assembly procedure that first uses sequence similarity (tBLASTn) to proteins of a model species to select allelic and fragmented contigs from all genotypes and then performs CAP3 clustering on a gene-by-gene basis. Thus, we simultaneously annotate putative orthologues for each protein of the model species, resolve allelic redundancy and fragmentation and create a de novo transcript sequence representing the consensus of all alleles present in the sequenced genotypes. We demonstrate the procedure using RNA-seq data from 14 genotypes of Lolium perenne to generate a reference transcriptome for gene discovery and translational research, to reveal the transcriptome-wide distribution and density of SNPs in an outbreeding crop and to illustrate the effect of polymorphisms on the assembly procedure. The results presented here illustrate that constructing a non-redundant reference sequence is essential for comparative genomics, orthology-based annotation and candidate gene selection but also for read mapping and subsequent polymorphism discovery and/or read count-based gene expression analysis. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  6. Molecular protein adaptor with genetically encoded interaction sites guiding the hierarchical assembly of plasmonically active nanoparticle architectures

    NASA Astrophysics Data System (ADS)

    Schreiber, Andreas; Huber, Matthias C.; Cölfen, Helmut; Schiller, Stefan M.

    2015-03-01

    The control over the defined assembly of nano-objects with nm-precision is important to create systems and materials with enhanced properties, for example, metamaterials. In nature, the precise assembly of inorganic nano-objects with unique features, for example, magnetosomes, is accomplished by efficient and reliable recognition schemes involving protein effectors. Here we present a molecular approach using protein-based ‘adaptors/connectors’ with genetically encoded interaction sites to guide the assembly and functionality of different plasmonically active gold nanoparticle architectures (AuNP). The interaction of the defined geometricaly shaped protein adaptors with the AuNP induces the self-assembly of nanoarchitectures ranging from AuNP encapsulation to one-dimensional chain-like structures, complex networks and stars. Synthetic biology and bionanotechnology are applied to co-translationally encode unnatural amino acids as additional site-specific modification sites to generate functionalized biohybrid nanoarchitectures. This protein adaptor-based nano-object assembly approach might be expanded to other inorganic nano-objects creating biohybrid materials with unique electronic, photonic, plasmonic and magnetic properties.

  7. On the local optimal solutions of metabolic regulatory networks using information guided genetic algorithm approach and clustering analysis.

    PubMed

    Zheng, Ying; Yeh, Chen-Wei; Yang, Chi-Da; Jang, Shi-Shang; Chu, I-Ming

    2007-08-31

    Biological information generated by high-throughput technology has made systems approach feasible for many biological problems. By this approach, optimization of metabolic pathway has been successfully applied in the amino acid production. However, in this technique, gene modifications of metabolic control architecture as well as enzyme expression levels are coupled and result in a mixed integer nonlinear programming problem. Furthermore, the stoichiometric complexity of metabolic pathway, along with strong nonlinear behaviour of the regulatory kinetic models, directs a highly rugged contour in the whole optimization problem. There may exist local optimal solutions wherein the same level of production through different flux distributions compared with global optimum. The purpose of this work is to develop a novel stochastic optimization approach-information guided genetic algorithm (IGA) to discover the local optima with different levels of modification of the regulatory loop and production rates. The novelties of this work include the information theory, local search, and clustering analysis to discover the local optima which have physical meaning among the qualified solutions.

  8. Potential of genetically modified oilseed rape for biofuels in Austria: Land use patterns and coexistence constraints could decrease domestic feedstock production

    PubMed Central

    Moser, Dietmar; Eckerstorfer, Michael; Pascher, Kathrin; Essl, Franz; Zulka, Klaus Peter

    2013-01-01

    Like other EU Member States, Austria will meet the substitution target of the EU European Renewable Energy Directive for transportation almost exclusively by first generation biofuels, primarily biodiesel from oilseed rape (OSR). Genetically modified (GM) plants have been promoted as a new option for biofuel production as they promise higher yield or higher quality feedstock. We tested implications of GM OSR application for biodiesel production in Austria by means of high resolution spatially explicit simulation of 140 different coexistence scenarios within six main OSR cropping regions in Austria (2400 km2). We identified structural land use characteristics such as field size, land use diversity, land holding patterns and the proportion of the target crop as the predominant factors which influence overall production of OSR in a coexistence scenario. Assuming isolation distances of 800 m and non-GM-OSR proportions of at least 10% resulted in a loss of area for cultivation of OSR in all study areas ranging from −4.5% to more than −25%, depending on the percentage of GM farmers and on the region. We could show that particularly the current primary OSR cropping regions are largely unsuitable for coexistence and would suffer from a net loss of OSR area even at isolation distances of 400 or 800 m. Coexistence constraints associated with application of GM OSR are likely to offset possible GM gains by substantially reducing farmland for OSR cultivation, thus contradicting the political aim to increase domestic OSR area to meet the combined demands of food, feed and biofuel production. PMID:26109750

  9. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity

    SciTech Connect

    Vargas, Carlos; Yan Di; Kestin, Larry L.; Krauss, Daniel; Lockman, David M.; Brabbins, Donald S.; Martinez, Alvaro A. . E-mail: amartinez@beaumont.edu

    2005-09-01

    Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage {<=} T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No

  10. Genetically Guided Statin Therapy

    DTIC Science & Technology

    2017-03-01

    genotype assessment were collected. Surveys were administered to identify self- reported subject demographics such as age, sex , race, ethnicity, education...privacy concerns. Demographic variables available on each patient include sex , ethnicity, race, marital status, and drug delivery program. The sample

  11. The cost effectiveness of genetic testing for CYP2C19 variants to guide thienopyridine treatment in patients with acute coronary syndromes: a New Zealand evaluation.

    PubMed

    Panattoni, Laura; Brown, Paul M; Te Ao, Braden; Webster, Mark; Gladding, Patrick

    2012-11-01

    A recent clinical trial has demonstrated that patients with acute coronary syndromes (ACS) and the reduced function allele CYP2C19*2 (*2 allele), who are treated with thienopyridines, have an increased risk of adverse cardiac events with clopidogrel, but not with prasugrel. The frequency of the *2 allele varies by ethnicity and the Maoris, Asians and Pacific Islanders of New Zealand have a relatively high incidence. Our objective was to evaluate, from a New Zealand health system perspective, the cost effectiveness of treating all ACS patients with generic clopidogrel compared with prasugrel, and also compared with the genetically guided strategy that *2 allele carriers receive prasugrel and non-carriers receive clopidogrel. A decision-tree model consisting of five health states (myocardial infarction, stroke, bleeding, stent thrombosis and cardiovascular death) was developed. Clinical outcome data (two TRITON-TIMI 38 genetic sub-studies) comparing clopidogrel and prasugrel for both *2 allele carriers and non-carriers were combined with the prevalence of the heterozygosity for the *2 allele in New Zealand Europeans (15%), Maoris (24%), Asians (29%) and Pacific Islanders (45%) to determine the predicted adverse event rate for the New Zealand population. National hospital diagnosis-related group (DRG) discharge codes were used to determine alternative adverse event rates, along with the costs of hospitalizations during the 15 months after patients presented with an ACS. The primary outcome measure was the incremental cost per QALY (calculated using literature-reported weights). Monte Carlo simulations and alternative scenario analysis based on both clinical trial and national hospital incidence were used. Additional analysis considered the overall TRITON-TIMI 38 rates. Costs (in New Zealand dollars [$NZ], year 2009 values) and benefits were discounted at 3% per annum. Actual hospital-based adverse event rates were higher than those reported in the TRITON-TIMI 38

  12. Constraint-based stereo matching

    NASA Technical Reports Server (NTRS)

    Kuan, D. T.

    1987-01-01

    The major difficulty in stereo vision is the correspondence problem that requires matching features in two stereo images. Researchers describe a constraint-based stereo matching technique using local geometric constraints among edge segments to limit the search space and to resolve matching ambiguity. Edge segments are used as image features for stereo matching. Epipolar constraint and individual edge properties are used to determine possible initial matches between edge segments in a stereo image pair. Local edge geometric attributes such as continuity, junction structure, and edge neighborhood relations are used as constraints to guide the stereo matching process. The result is a locally consistent set of edge segment correspondences between stereo images. These locally consistent matches are used to generate higher-level hypotheses on extended edge segments and junctions to form more global contexts to achieve global consistency.

  13. Genetics

    USDA-ARS?s Scientific Manuscript database

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  14. Genetics

    USDA-ARS?s Scientific Manuscript database

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  15. Web-based software tool for constraint-based design specification of synthetic biological systems.

    PubMed

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

    miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

  16. Population genetics data help to guide the conservation of palm species with small population sizes and fragmented habitats in Madagascar

    PubMed Central

    Rakotoarinivo, Mijoro; Rajaovelona, Landy R.; Clubbe, Colin

    2017-01-01

    Background The need to incorporate genetic data into conservation management decisions is increasingly recognised. However, many published studies represent a ‘gold standard’ of sampling, techniques, and analyses. Such rigour is often not possible with limited funding and resourcing available for developing plans for the increasing number of threatened species requiring conservation management. Two endemic palm species of the Itremo Massif in central Madagascar, Dypsis ambositrae and D. decipiens, are known to be threatened with extinction and conservation management for these species is a priority for the newly created protected area in the region. Methods The genetic diversity of these two species was studied using the relatively low-cost and rapid AFLP technique. DNA fragments generated using three primer combinations were analysed for 20 and 50 individuals of the two species, respectively, from across their ranges. Results Genetic diversity was relatively low for both species. The two sites where the highly restricted D. ambositrae grows were found to be genetically distinct (although overall heterozygosity was low). Despite having a much wider distribution and relatively large population, D. decipiens did not show clear geographical nor genetic groupings and had similarly low genetic heterozygosity to D. ambositrae. Discussion and Recommendations With so few individuals remaining in the wild and two genetically distinct subpopulations, it is recommended that both sites of D. ambositrae are conserved and that seed are collected from both for ex situ conservation and potential future reintroduction. It may be less important to focus resources on conserving or collecting ex situ material from all sites where D. decipiens is found, as the genetic diversity represented by each subpopulation is limited and increasing sampling may not protect significantly higher levels of genetic diversity. This study provides data that inform and support conservation decisions

  17. Population genetics data help to guide the conservation of palm species with small population sizes and fragmented habitats in Madagascar.

    PubMed

    Gardiner, Lauren M; Rakotoarinivo, Mijoro; Rajaovelona, Landy R; Clubbe, Colin

    2017-01-01

    The need to incorporate genetic data into conservation management decisions is increasingly recognised. However, many published studies represent a 'gold standard' of sampling, techniques, and analyses. Such rigour is often not possible with limited funding and resourcing available for developing plans for the increasing number of threatened species requiring conservation management. Two endemic palm species of the Itremo Massif in central Madagascar, Dypsis ambositrae and D. decipiens, are known to be threatened with extinction and conservation management for these species is a priority for the newly created protected area in the region. The genetic diversity of these two species was studied using the relatively low-cost and rapid AFLP technique. DNA fragments generated using three primer combinations were analysed for 20 and 50 individuals of the two species, respectively, from across their ranges. Genetic diversity was relatively low for both species. The two sites where the highly restricted D. ambositrae grows were found to be genetically distinct (although overall heterozygosity was low). Despite having a much wider distribution and relatively large population, D. decipiens did not show clear geographical nor genetic groupings and had similarly low genetic heterozygosity to D. ambositrae. With so few individuals remaining in the wild and two genetically distinct subpopulations, it is recommended that both sites of D. ambositrae are conserved and that seed are collected from both for ex situ conservation and potential future reintroduction. It may be less important to focus resources on conserving or collecting ex situ material from all sites where D. decipiens is found, as the genetic diversity represented by each subpopulation is limited and increasing sampling may not protect significantly higher levels of genetic diversity. This study provides data that inform and support conservation decisions taken for both species within this region, and in the

  18. Genetic variation and covariation for resistance and tolerance to Cucumber mosaic virus in Mimulus guttatus (Phrymaceae): a test for costs and constraints.

    PubMed

    Carr, D E; Murphy, J F; Eubanks, M D

    2006-01-01

    Genetic variation for resistance and tolerance to pathogens may be maintained by costs represented as genetic tradeoffs between these traits and fitness. The evolution of resistance and tolerance also may be constrained by negative genetic correlations between these defense systems. Using a complete diallel, we measured genetic variation and covariation for and among performance, resistance, and tolerance traits in Mimulus guttatus challenged with a generalist pathogen, Cucumber mosaic virus (CMV). Viral coat protein was detected by enzyme-linked immunosorbent assay (ELISA) in all inoculated plants, indicating that all plants were susceptible to infection, although the ELISA absorbance varied quantitatively across plants. Plants inoculated with CMV had significantly reduced aboveground biomass and flower production relative to controls, although date of first flower was unaffected by infection. All three of these performance traits showed moderate to high narrow-sense heritability (h2 = 0.32-0.62) in both inoculated and control plants. We found phenotypic variation for both tolerance of and resistance to our strain of CMV, but both displayed very low narrow-sense heritability (h2 < 0.03). We found no evidence of a trade-off between resistance and tolerance. We also found no evidence for a cost of resistance or tolerance. In fact, a significant genetic correlation suggested that plants that were large when healthy had the greatest tolerance when infected. Significant, positive genetic correlations found between performance of uninfected and infected plants suggested that selection would likely favor the same M. guttatus genotypes whether CMV is present or not.

  19. Convergence, adaptation, and constraint.

    PubMed

    Losos, Jonathan B

    2011-07-01

    Convergent evolution of similar phenotypic features in similar environmental contexts has long been taken as evidence of adaptation. Nonetheless, recent conceptual and empirical developments in many fields have led to a proliferation of ideas about the relationship between convergence and adaptation. Despite criticism from some systematically minded biologists, I reaffirm that convergence in taxa occupying similar selective environments often is the result of natural selection. However, convergent evolution of a trait in a particular environment can occur for reasons other than selection on that trait in that environment, and species can respond to similar selective pressures by evolving nonconvergent adaptations. For these reasons, studies of convergence should be coupled with other methods-such as direct measurements of selection or investigations of the functional correlates of trait evolution-to test hypotheses of adaptation. The independent acquisition of similar phenotypes by the same genetic or developmental pathway has been suggested as evidence of constraints on adaptation, a view widely repeated as genomic studies have documented phenotypic convergence resulting from change in the same genes, sometimes even by the same mutation. Contrary to some claims, convergence by changes in the same genes is not necessarily evidence of constraint, but rather suggests hypotheses that can test the relative roles of constraint and selection in directing phenotypic evolution. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  20. Mapping genetic research in non-communicable disease publications in selected Arab countries: first step towards a guided research agenda.

    PubMed

    Jamaluddine, Zeina; Sibai, Abla Mehio; Othman, Shahd; Yazbek, Soha

    2016-11-10

    In the Arab world, intervention and policy response to non-communicable diseases (NCD) has been weak despite extensive epidemiological evidence highlighting the alarmingly increased prevalence of chronic diseases. Generating genetic information is one key component to promote efficient disease management strategies. This study undertook a scoping review to generate the profile of the undertaken research on genetics of NCD publications in selected Arab countries. An analysis of the research produced examined the extent, range, nature, topic and methods of published research. The study aimed at identifying the gaps in genetic NCD research to inform policy action for NCD prevention and control. The scoping review was conducted based on the five-stage methodological framework and included countries in Arab region selected to represent various economies and epidemiological transitions. The search identified 555 articles that focus on genetics-NCD research in the selected Arab countries over the duration of this study (January 2000 to December 2013). The most commonly conducted research was descriptive and clinically focused, rather than etiologically focused. Country-specific carrier and risk screening studies were not among the top research designs. The genetic component of certain highly heritable diseases, as well as diabetes, obesity, hypertension, chronic lung dysfunction and metabolic syndrome were all under investigated. This scoping review identified gaps for further research in the context of bioinformatics and genome-wide association studies. Genetic research in the Arab region has to be redirected towards NCDs with the highest morbidity, heritability and health burden within each country. A focused research plan to include community genetics is required for its proper integration in the Arab community.

  1. The use of quantum molecular calculations to guide a genetic algorithm: a way to search for new chemistry.

    PubMed

    Durrant, Marcus C

    2007-01-01

    The process of gene-based molecular evolution has been simulated in silico by using massively parallel density functional theory quantum calculations, coupled with a genetic algorithm, to test for fitness with respect to a target chemical reaction in populations of genetically encoded molecules. The goal of this study was the identification of transition-metal complexes capable of mediating a known reaction, namely the cleavage of N(2) to give the metal nitride. Each complex within the search space was uniquely specified by a nanogene consisting of an eight-digit number. Propagation of an individual nanogene into successive generations was determined by the fitness of its phenotypic molecule to perform the target reaction and new generations were created by recombination and mutation of surviving nanogenes. In its simplest implementation, the quantum-directed genetic algorithm (QDGA) quickly located a local minimum on the evolutionary fitness hypersurface, but proved incapable of progressing towards the global minimum. A strategy for progressing beyond local minima consistent with the Darwinian paradigm by the use of environmental variations coupled with mass extinctions was therefore developed. This allowed for the identification of nitriding complexes that are very closely related to known examples from the chemical literature. Examples of mutations that appear to be beneficial at the genetic level but prove to be harmful at the phenotypic level are described. As well as revealing fundamental aspects of molecular evolution, QDGA appears to be a powerful tool for the identification of lead compounds capable of carrying out a target chemical reaction.

  2. Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

    PubMed

    Wise, Michael J; Rausher, Mark D

    2013-06-01

    Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance.

  3. Hydroeconomic optimization of reservoir management under downstream water quality constraints

    NASA Astrophysics Data System (ADS)

    Davidsen, Claus; Liu, Suxia; Mo, Xingguo; Holm, Peter E.; Trapp, Stefan; Rosbjerg, Dan; Bauer-Gottwein, Peter

    2015-10-01

    A hydroeconomic optimization approach is used to guide water management in a Chinese river basin with the objectives of meeting water quantity and water quality constraints, in line with the China 2011 No. 1 Policy Document and 2015 Ten-point Water Plan. The proposed modeling framework couples water quantity and water quality management and minimizes the total costs over a planning period assuming stochastic future runoff. The outcome includes cost-optimal reservoir releases, groundwater pumping, water allocation, wastewater treatments and water curtailments. The optimization model uses a variant of stochastic dynamic programming known as the water value method. Nonlinearity arising from the water quality constraints is handled with an effective hybrid method combining genetic algorithms and linear programming. Untreated pollutant loads are represented by biochemical oxygen demand (BOD), and the resulting minimum dissolved oxygen (DO) concentration is computed with the Streeter-Phelps equation and constrained to match Chinese water quality targets. The baseline water scarcity and operational costs are estimated to 15.6 billion CNY/year. Compliance to water quality grade III causes a relatively low increase to 16.4 billion CNY/year. Dilution plays an important role and increases the share of surface water allocations to users situated furthest downstream in the system. The modeling framework generates decision rules that result in the economically efficient strategy for complying with both water quantity and water quality constraints.

  4. Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds

    PubMed Central

    Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa

    2015-01-01

    Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates. PMID:25809972

  5. Genetically Guided Statin Therapy on Statin Perceptions, Adherence, and Cholesterol Lowering: A Pilot Implementation Study in Primary Care Patients

    PubMed Central

    Li, Josephine H.; Joy, Scott V.; Haga, Susanne B.; Orlando, Lori A.; Kraus, William E.; Ginsburg, Geoffrey S.; Voora, Deepak

    2014-01-01

    Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown. Primary care patients (n = 58) who were nonadherent to statins and their providers received SLCO1B1*5 genotyping and guided recommendations via the electronic medical record (EMR). The primary outcome was the change in Beliefs about Medications Questionnaire, which measured patients’ perceived needs for statins and concerns about adverse effects, measured before and after SLCO1B1*5 results. Concurrent controls (n = 59) were identified through the EMR to compare secondary outcomes: new statin prescriptions, statin utilization, and change in LDL-cholesterol (LDL-c). GGST patients had trends (p = 0.2) towards improved statin necessity and concerns. The largest changes were the “need for statin to prevent sickness” (p < 0.001) and “concern for statin to disrupt life” (p = 0.006). GGST patients had more statin prescriptions (p < 0.001), higher statin use (p < 0.001), and greater decrease in LDL-c (p = 0.059) during follow-up. EMR delivery of SLCO1B1*5 results and recommendations is feasible in the primary care setting. This novel intervention may improve patients’ perceptions of statins and physician behaviors that promote higher statin adherence and lower LDL-c. PMID:25563221

  6. A Fukui function-guided genetic algorithm. Assessment on structural prediction of Sin (n = 12-20) clusters.

    PubMed

    Yañez, Osvaldo; Vásquez-Espinal, Alejandro; Inostroza, Diego; Ruiz, Lina; Pino-Rios, Ricardo; Tiznado, William

    2017-07-15

    Theoretical studies are essential for the structural characterization of clusters, when it comes to rationalize their unique size-dependent properties and composition. However, the rapid growth of local minima on the potential energy surface (PES), with respect to cluster size, makes the candidate identification a challenging undertaking. In this article, we introduce a hybrid strategy to explore the PES of clusters. This proposal involves the use of a biased initial population of a genetic algorithm procedure. Each individual in this population is built by assembling small fragments, according to the best matching of the Fukui function. The performance of a genetic algorithm procedure. The performance of the method is assessed on the PES exploration of medium-sized Sin clusters (n = 12-20). The most relevant results are: (a) the method converges at almost half of the time used by the canonical version of the GA and, (b) in all the studied cases, with the exception of Si13 and Si16 , the method allowed to identify the global minimum (GM) and other important low-lying structures. Additionally, the apparent deficiency of the proposal to identify the GM was corrected when a Si atom, or other low-lying isomers, were considered to build the clusters. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. New knowledge-based genetic algorithm for excavator boom structural optimization

    NASA Astrophysics Data System (ADS)

    Hua, Haiyan; Lin, Shuwen

    2014-03-01

    Due to the insufficiency of utilizing knowledge to guide the complex optimal searching, existing genetic algorithms fail to effectively solve excavator boom structural optimization problem. To improve the optimization efficiency and quality, a new knowledge-based real-coded genetic algorithm is proposed. A dual evolution mechanism combining knowledge evolution with genetic algorithm is established to extract, handle and utilize the shallow and deep implicit constraint knowledge to guide the optimal searching of genetic algorithm circularly. Based on this dual evolution mechanism, knowledge evolution and population evolution can be connected by knowledge influence operators to improve the configurability of knowledge and genetic operators. Then, the new knowledge-based selection operator, crossover operator and mutation operator are proposed to integrate the optimal process knowledge and domain culture to guide the excavator boom structural optimization. Eight kinds of testing algorithms, which include different genetic operators, are taken as examples to solve the structural optimization of a medium-sized excavator boom. By comparing the results of optimization, it is shown that the algorithm including all the new knowledge-based genetic operators can more remarkably improve the evolutionary rate and searching ability than other testing algorithms, which demonstrates the effectiveness of knowledge for guiding optimal searching. The proposed knowledge-based genetic algorithm by combining multi-level knowledge evolution with numerical optimization provides a new effective method for solving the complex engineering optimization problem.

  8. Genetic algorithm guided population pharmacokinetic model development for simvastatin, concurrently or non-concurrently co-administered with amlodipine.

    PubMed

    Chaturvedula, Ayyappa; Sale, Mark E; Lee, Howard

    2014-02-01

    An automated model development was performed for simvastatin, co-administered with amlodipine concurrently or non-concurrently (i.e., 4 hours later) in 17 patients with coexisting hyperlipidemia and hypertension. The single objective hybrid genetic algorithm (SOHGA) was implemented in the NONMEM software by defining the search space for structural, statistical and covariate models. Candidate models obtained from the SOHGA runs were further assessed for biological plausibility and the precision of parameter estimates, followed by traditional backward elimination process for model refinement. The final population pharmacokinetic model shows that the elimination rate constant for simvastatin acid, the active form by hydrolysis of its lactone prodrug (i.e., simvastatin), is only 44% in the concurrent amlodipine administration group compared with the non-concurrent group. The application of SOHGA for automated model selection, combined with traditional model selection strategies, appears to save time for model development, which also can generate new hypotheses that are biologically more plausible.

  9. Dynamic Constraint Satisfaction with Reasonable Global Constraints

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy

    2003-01-01

    Previously studied theoretical frameworks for dynamic constraint satisfaction problems (DCSPs) employ a small set of primitive operators to modify a problem instance. They do not address the desire to model problems using sophisticated global constraints, and do not address efficiency questions related to incremental constraint enforcement. In this paper, we extend a DCSP framework to incorporate global constraints with flexible scope. A simple approach to incremental propagation after scope modification can be inefficient under some circumstances. We characterize the cases when this inefficiency can occur, and discuss two ways to alleviate this problem: adding rejection variables to the scope of flexible constraints, and adding new features to constraints that permit increased control over incremental propagation.

  10. Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds.

    PubMed

    Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa; Hirai, Itaru

    2015-06-01

    Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Genetics Home Reference: otulipenia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions otulipenia otulipenia Enable Javascript to ...

  12. The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV.

    PubMed

    Schackman, Bruce R; Scott, Callie A; Walensky, Rochelle P; Losina, Elena; Freedberg, Kenneth A; Sax, Paul E

    2008-10-01

    To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States. Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction among patients taking abacavir testing HLA-B*5701 positive and negative were from the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial study. The monthly costs of abacavir-based and tenofovir-based regimens were $1135 and $1139, respectively; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis. Simulated cohort of patients initiating HIV therapy. The interventions are first-line abacavir, lamivudine, and efavirenz without pretreatment HLA-B*5701 testing; the same regimen with HLA-B*5701 testing; and first-line tenofovir, emtricitabine, and efavirenz. Quality-adjusted life years and lifetime medical costs discounted at 3% per annum, cost-effectiveness ratios ($/QALY). Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted quality-adjusted life years, and $472,200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at an incremental cost of $110, resulting in a cost-effectiveness ratio of $36,700/QALY compared with no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving quality-adjusted life expectancy. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701. Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment.

  13. Individuals' interpretation of constraints: a new perspective on existing theory

    Treesearch

    Po-Ju Chen; Deborah Kerstetter; Linda Caldwell

    2001-01-01

    The travel decision-making process is influenced by a number of factors. One of the most important yet infrequently studied factors is "perceived constraints." Nearly a decade ago Crawford, Jackson and Godbey (1991) developed a framework to guide constraints research. Numerous authors have utilized this framework but results have suggested that individuals...

  14. Constraint monitoring in TOSCA

    NASA Technical Reports Server (NTRS)

    Beck, Howard

    1992-01-01

    The Job-Shop Scheduling Problem (JSSP) deals with the allocation of resources over time to factory operations. Allocations are subject to various constraints (e.g., production precedence relationships, factory capacity constraints, and limits on the allowable number of machine setups) which must be satisfied for a schedule to be valid. The identification of constraint violations and the monitoring of constraint threats plays a vital role in schedule generation in terms of the following: (1) directing the scheduling process; and (2) informing scheduling decisions. This paper describes a general mechanism for identifying constraint violations and monitoring threats to the satisfaction of constraints throughout schedule generation.

  15. Constraint Based Modeling Going Multicellular.

    PubMed

    Martins Conde, Patricia do Rosario; Sauter, Thomas; Pfau, Thomas

    2016-01-01

    Constraint based modeling has seen applications in many microorganisms. For example, there are now established methods to determine potential genetic modifications and external interventions to increase the efficiency of microbial strains in chemical production pipelines. In addition, multiple models of multicellular organisms have been created including plants and humans. While initially the focus here was on modeling individual cell types of the multicellular organism, this focus recently started to switch. Models of microbial communities, as well as multi-tissue models of higher organisms have been constructed. These models thereby can include different parts of a plant, like root, stem, or different tissue types in the same organ. Such models can elucidate details of the interplay between symbiotic organisms, as well as the concerted efforts of multiple tissues and can be applied to analyse the effects of drugs or mutations on a more systemic level. In this review we give an overview of the recent development of multi-tissue models using constraint based techniques and the methods employed when investigating these models. We further highlight advances in combining constraint based models with dynamic and regulatory information and give an overview of these types of hybrid or multi-level approaches.

  16. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy

    PubMed Central

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-01-01

    Abstract Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection. The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance. A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by 13C-urea breath test after at least 4 weeks when treatment was finished. Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15

  17. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    PubMed

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

  18. On Random Betweenness Constraints

    NASA Astrophysics Data System (ADS)

    Goerdt, Andreas

    Ordering constraints are analogous to instances of the satisfiability problem in conjunctive normalform, but instead of a boolean assignment we consider a linear ordering of the variables in question. A clause becomes true given a linear ordering iff the relative ordering of its variables obeys the constraint considered.

  19. Creating Positive Task Constraints

    ERIC Educational Resources Information Center

    Mally, Kristi K.

    2006-01-01

    Constraints are characteristics of the individual, the task, or the environment that mold and shape movement choices and performances. Constraints can be positive--encouraging proficient movements or negative--discouraging movement or promoting ineffective movements. Physical educators must analyze, evaluate, and determine the effect various…

  20. Credit Constraints in Education

    ERIC Educational Resources Information Center

    Lochner, Lance; Monge-Naranjo, Alexander

    2012-01-01

    We review studies of the impact of credit constraints on the accumulation of human capital. Evidence suggests that credit constraints have recently become important for schooling and other aspects of households' behavior. We highlight the importance of early childhood investments, as their response largely determines the impact of credit…

  1. Creating Positive Task Constraints

    ERIC Educational Resources Information Center

    Mally, Kristi K.

    2006-01-01

    Constraints are characteristics of the individual, the task, or the environment that mold and shape movement choices and performances. Constraints can be positive--encouraging proficient movements or negative--discouraging movement or promoting ineffective movements. Physical educators must analyze, evaluate, and determine the effect various…

  2. Constraint Reasoning Over Strings

    NASA Technical Reports Server (NTRS)

    Koga, Dennis (Technical Monitor); Golden, Keith; Pang, Wanlin

    2003-01-01

    This paper discusses an approach to representing and reasoning about constraints over strings. We discuss how many string domains can often be concisely represented using regular languages, and how constraints over strings, and domain operations on sets of strings, can be carried out using this representation.

  3. Credit Constraints in Education

    ERIC Educational Resources Information Center

    Lochner, Lance; Monge-Naranjo, Alexander

    2012-01-01

    We review studies of the impact of credit constraints on the accumulation of human capital. Evidence suggests that credit constraints have recently become important for schooling and other aspects of households' behavior. We highlight the importance of early childhood investments, as their response largely determines the impact of credit…

  4. Reduction of Constraints: Applicability of the Homogeneity Constraint for Macrobatch 3

    SciTech Connect

    Peeler, D.K.

    2001-02-15

    The Product Composition Control System (PCCS) is used to determine the acceptability of each batch of Defense Waste Processing Facility (DWPF) melter feed in the Slurry Mix Evaporator (SME). This control system imposes several constraints on the composition of the contents of the SME to define acceptability. These constraints relate process or product properties to composition via prediction models. A SME batch is deemed acceptable if its sample composition measurements lead to acceptable property predictions after accounting for modeling, measurement and analytic uncertainties. The baseline document guiding the use of these data and models is ''SME Acceptability Determination for DWPF Process Control (U)'' by Brown and Postles [1996]. A minimum of three PCCS constraints support the prediction of the glass durability from a given SME batch. The Savannah River Technology Center (SRTC) is reviewing all of the PCCS constraints associated with durability. The purpose of this review is to revisit these constraints in light of the additional knowledge gained since the beginning of radioactive operations at DWPF and to identify any supplemental studies needed to amplify this knowledge so that redundant or overly conservative constraints can be eliminated or replaced by more appropriate constraints.

  5. Genetics Home Reference: renal hypouricemia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions renal hypouricemia renal hypouricemia Enable ...

  6. Genetics Home Reference: Friedreich ataxia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Friedreich ataxia Friedreich ataxia Enable ...

  7. Genetics Home Reference: craniometaphyseal dysplasia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions craniometaphyseal dysplasia craniometaphyseal dysplasia Enable ...

  8. Genetics Home Reference: Sotos syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Sotos syndrome Sotos syndrome Enable ...

  9. The automatic neutron guide optimizer guide_bot

    NASA Astrophysics Data System (ADS)

    Bertelsen, Mads

    2017-09-01

    The guide optimization software guide_bot is introduced, the main purpose of which is to reduce the time spent programming when performing numerical optimization of neutron guides. A limited amount of information on the overall guide geometry and a figure of merit describing the desired beam is used to generate the code necessary to solve the problem. A generated McStas instrument file performs the Monte Carlo ray-tracing, which is controlled by iFit optimization scripts. The resulting optimal guide is thoroughly characterized, both in terms of brilliance transfer from an idealized source and on a more realistic source such as the ESS Butterfly moderator. Basic MATLAB knowledge is required from the user, but no experience with McStas or iFit is necessary. This paper briefly describes how guide_bot is used and some important aspects of the code. A short validation against earlier work is performed which shows the expected agreement. In addition a scan over the vertical divergence requirement, where individual guide optimizations are performed for each corresponding figure of merit, provides valuable data on the consequences of this parameter. The guide_bot software package is best suited for the start of an instrument design project as it excels at comparing a large amount of different guide alternatives for a specific set of instrument requirements, but is still applicable in later stages as constraints can be used to optimize more specific guides.

  10. Analysis of Production Constraints at NADEP Alameda; A TQL Approach

    DTIC Science & Technology

    1993-06-01

    thesis uses the Theory of Constraints as espoused by Eliyahu M. Goldratt . as the guiding theory for analyzing barriers to throughput. The analytical...Theory of Constraints, as espoused by Goldratt [Ref. 7] provides a management methodology and new measuring units. To provide the background and show...effects of evaluation of performance is nourishment of short-term thinking and short-time performance." Goldratt [Ref. 1i] says: "tell me how you measure

  11. Dynamic Constraints Networks

    DTIC Science & Technology

    1989-10-31

    static approach to constrained networks has been used to develop a dynamic theory of constraint networks for problem solving. The scientific results of this development resulted in six scientific publications . (KT)

  12. Genes and Surroundings: Teacher's Guide.

    ERIC Educational Resources Information Center

    Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

    This teacher's guide is intended to be used with "Genes and Surroundings," an activity unit on human and medical genetics for junior high and middle school students. The unit emphasizes variability and diversity in genetics and is organized around five themes: (1) individuality; (2) continuity; (3) variability in relation to others; (4)…

  13. Computer Processing 10-20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of computer processing. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials…

  14. Basic Business 20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of basic business. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials…

  15. Law 20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of law. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials include a…

  16. Computer Processing 10-20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of computer processing. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials…

  17. Office Procedures 20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of office procedures. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials…

  18. Marketing 20-30. Business Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Alberta Dept. of Education, Edmonton. Curriculum Branch.

    This curriculum guide is one of nine such guides developed for an Alberta high school business education program. Its content covers the main subject area or strand of marketing. Subject to the constraints outlined in the guide, the modules are to be formatted into three- or four-credit courses within each strand. Introductory materials include a…

  19. Deployment Guide

    DTIC Science & Technology

    1994-02-01

    family/unit briefings (to include POA/wills/ consumer law /insurance war clauses) - Provide fill-in-blank sheets to send coordinators of pre- deployment...services. 2. SGLI designations and "By Law" implications. 3. Wills for both spouses. 4. Powers of Attorney. 5. Consumer law issues. 1-7 B. Typically...Relief Act JA 261 Real Property Guide JA 262 Wills Guide JA 263 Family Law Guide JA 265 Consumer Law Guide JA 267 Legal Assistance Office Directory

  20. Neutron guide

    DOEpatents

    Greene, Geoffrey L.

    1999-01-01

    A neutron guide in which lengths of cylindrical glass tubing have rectangular glass plates properly dimensioned to allow insertion into the cylindrical glass tubing so that a sealed geometrically precise polygonal cross-section is formed in the cylindrical glass tubing. The neutron guide provides easier alignment between adjacent sections than do the neutron guides of the prior art.

  1. Disclosing Huntington's Genetic Testing Results in the Context of Intellectual Disability and Guardianship: Using the Family Illness Narrative to Guide the Flow of Information.

    PubMed

    Warren, Mark B; Schak, Kathryn M

    2016-10-15

    A diagnosis of Huntington's disease has broad social, vocational, reproductive and psychological implications. The ability to accurately diagnose the illness via genetic testing is not new. However, given a persistent lack of robustly effective interventions, it remains an area of ethical concern. The difficulty is compounded in cases of intellectual disability. This paper presents a case of genetic testing for Huntington's disease conducted on a patient with intellectual disability with guardian consent, but without the patient's direct knowledge and how the family illness narrative and psychiatric care were employed in the eventual disclosure of the patient's diagnosis and subsequent management.

  2. Constraints on relaxion windows

    NASA Astrophysics Data System (ADS)

    Choi, Kiwoon; Im, Sang Hui

    2016-12-01

    We examine the low energy phenomenology of the relaxion solution to the weak scale hierarchy problem. Assuming that the Hubble friction is responsible for a dissipation of the relaxion energy, we identify the cosmological relaxion window which corresponds to the parameter region compatible with a given value of the acceptable number of inflationary e-foldings. We then discuss a variety of observational constraints on the relaxion window, including those from astrophysical and cosmological considerations. We find that majority of the parameter space with a relaxion mass m ϕ ≳ 100 eV or a relaxion decay constant f ≲107GeV is excluded by existing constraints. There is an interesting parameter region with m ϕ ˜ 0 .2 - 10 GeV and f ˜ few - 200 TeV, which is allowed by existing constraints, but can be probed soon by future beam dump experiments such as the SHiP experiment, or by improved EDM experiments.

  3. Superselection from canonical constraints

    NASA Astrophysics Data System (ADS)

    Hall, Michael J. W.

    2004-08-01

    The evolution of both quantum and classical ensembles may be described via the probability density P on configuration space, its canonical conjugate S, and an ensemble Hamiltonian \\skew3\\tilde{H}[P,S] . For quantum ensembles this evolution is, of course, equivalent to the Schrödinger equation for the wavefunction, which is linear. However, quite simple constraints on the canonical fields P and S correspond to nonlinear constraints on the wavefunction. Such constraints act to prevent certain superpositions of wavefunctions from being realized, leading to superselection-type rules. Examples leading to superselection for energy, spin direction and 'classicality' are given. The canonical formulation of the equations of motion, in terms of a probability density and its conjugate, provides a universal language for describing classical and quantum ensembles on both continuous and discrete configuration spaces, and is briefly reviewed in an appendix.

  4. Constraint algebra in bigravity

    SciTech Connect

    Soloviev, V. O.

    2015-07-15

    The number of degrees of freedom in bigravity theory is found for a potential of general form and also for the potential proposed by de Rham, Gabadadze, and Tolley (dRGT). This aim is pursued via constructing a Hamiltonian formalismand studying the Poisson algebra of constraints. A general potential leads to a theory featuring four first-class constraints generated by general covariance. The vanishing of the respective Hessian is a crucial property of the dRGT potential, and this leads to the appearance of two additional second-class constraints and, hence, to the exclusion of a superfluous degree of freedom—that is, the Boulware—Deser ghost. The use of a method that permits avoiding an explicit expression for the dRGT potential is a distinctive feature of the present study.

  5. Effect of spatial constraints on Hardy-Weinberg equilibrium

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Shin; Su, Yi-Cheng; Pan, Wei

    2016-01-01

    Panmixia is a key issue in maintaining genetic diversity, which facilitates evolutionary potential during environmental changes. Additionally, conservation biologists suggest the importance of avoiding small or subdivided populations, which are prone to losing genetic diversity. In this paper, computer simulations were performed to the genetic drift of neutral alleles in random mating populations with or without spatial constraints by randomly choosing a mate among the closest neighbours. The results demonstrated that the number of generations required for the neutral allele to become homozygous (Th) varied proportionally to the population size and also strongly correlated with spatial constraints. The average Th for populations of the same size with spatial constraints was approximately one-and-a-half times longer than without constraints. With spatial constraints, homozygous population clusters formed, which reduced local diversity but preserved global diversity. Therefore, panmixia might be harmful in preserving the genetic diversity of an entire population. The results also suggested that the gene flow or gene exchange among the subdivided populations must be carefully processed to restrict diseases transmission or death during transportation and to monitor the genetic diversity. The application of this concept to similar systems, such as information transfer among peers, is also discussed.

  6. Effect of spatial constraints on Hardy-Weinberg equilibrium

    PubMed Central

    Chen, Yi-Shin; Su, Yi-Cheng; Pan, Wei

    2016-01-01

    Panmixia is a key issue in maintaining genetic diversity, which facilitates evolutionary potential during environmental changes. Additionally, conservation biologists suggest the importance of avoiding small or subdivided populations, which are prone to losing genetic diversity. In this paper, computer simulations were performed to the genetic drift of neutral alleles in random mating populations with or without spatial constraints by randomly choosing a mate among the closest neighbours. The results demonstrated that the number of generations required for the neutral allele to become homozygous (Th) varied proportionally to the population size and also strongly correlated with spatial constraints. The average Th for populations of the same size with spatial constraints was approximately one-and-a-half times longer than without constraints. With spatial constraints, homozygous population clusters formed, which reduced local diversity but preserved global diversity. Therefore, panmixia might be harmful in preserving the genetic diversity of an entire population. The results also suggested that the gene flow or gene exchange among the subdivided populations must be carefully processed to restrict diseases transmission or death during transportation and to monitor the genetic diversity. The application of this concept to similar systems, such as information transfer among peers, is also discussed. PMID:26771073

  7. Guide star probabilities

    NASA Technical Reports Server (NTRS)

    Soneira, R. M.; Bahcall, J. N.

    1981-01-01

    Probabilities are calculated for acquiring suitable guide stars (GS) with the fine guidance system (FGS) of the space telescope. A number of the considerations and techniques described are also relevant for other space astronomy missions. The constraints of the FGS are reviewed. The available data on bright star densities are summarized and a previous error in the literature is corrected. Separate analytic and Monte Carlo calculations of the probabilities are described. A simulation of space telescope pointing is carried out using the Weistrop north galactic pole catalog of bright stars. Sufficient information is presented so that the probabilities of acquisition can be estimated as a function of position in the sky. The probability of acquiring suitable guide stars is greatly increased if the FGS can allow an appreciable difference between the (bright) primary GS limiting magnitude and the (fainter) secondary GS limiting magnitude.

  8. The symmetry energy: Predictions and constraints

    NASA Astrophysics Data System (ADS)

    Sammarruca, Francesca

    2017-09-01

    After recalling basic phenomenological features of isospin asymmetric nuclear matter, we review predictions for the interaction part of the symmetry energy obtained from different microscopic approaches. The predictions are compared to updated constraints extracted from heavy-ion (HI) reaction observables of a recent GSI experiment. The discussion is extended to the neutron skin thickness in 208Pb and its relation to the density derivative of the symmetry energy. We underline the importance of giving proper consideration to the theoretical uncertainties of microscopic predictions in order to guide phenomenological analyses. In the end, we report briefly on preliminary neutron star calculations based on chiral nuclear forces and outline future plans.

  9. "Atypical" atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy-a diagnostic guide.

    PubMed

    Stamelou, Maria; Quinn, Niall P; Bhatia, Kailash P

    2013-08-01

    Recently, a number of genetic parkinsonian conditions have been recognized that share some features with the clinical syndromes of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA), the classic phenotypic templates of atypical parkinsonism. For example, patients with progranulin, dynactin, or ATP13A gene mutations may have vertical supranuclear gaze palsy. This has made differential diagnosis difficult for practitioners. In this review, our goal is to make clinicians aware of these genetic disorders and provide clinical clues and syndromic associations, as well as investigative features, that may help in diagnosing these disorders. The correct identification of these patients has important clinical, therapeutic, and research implications. © 2013 Movement Disorder Society.

  10. Background constraints in the infinite tension limit of the heterotic string

    NASA Astrophysics Data System (ADS)

    Azevedo, Thales; Jusinskas, Renann Lipinski

    2016-08-01

    In this work we investigate the classical constraints imposed on the supergravity and super Yang-Mills backgrounds in the α' → 0 limit of the heterotic string using the pure spinor formalism. Guided by the recently observed sectorization of the model, we show that all the ten-dimensional constraints are elegantly obtained from the single condition of nilpotency of the BRST charge.

  11. A constraint algorithm for singular Lagrangians subjected to nonholonomic constraints

    SciTech Connect

    de Leon, M.; de Diego, D.M.

    1997-06-01

    We construct a constraint algorithm for singular Lagrangian systems subjected to nonholonomic constraints which generalizes that of Dirac for constrained Hamiltonian systems. {copyright} {ital 1997 American Institute of Physics.}

  12. Breaking evolutionary constraint with a tradeoff ratchet

    PubMed Central

    de Vos, Marjon G. J.; Dawid, Alexandre; Sunderlikova, Vanda; Tans, Sander J.

    2015-01-01

    Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype–environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor–operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that cross-environmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance. PMID:26567153

  13. A Framework for Dynamic Constraint Reasoning Using Procedural Constraints

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari K.; Frank, Jeremy D.

    1999-01-01

    Many complex real-world decision and control problems contain an underlying constraint reasoning problem. This is particularly evident in a recently developed approach to planning, where almost all planning decisions are represented by constrained variables. This translates a significant part of the planning problem into a constraint network whose consistency determines the validity of the plan candidate. Since higher-level choices about control actions can add or remove variables and constraints, the underlying constraint network is invariably highly dynamic. Arbitrary domain-dependent constraints may be added to the constraint network and the constraint reasoning mechanism must be able to handle such constraints effectively. Additionally, real problems often require handling constraints over continuous variables. These requirements present a number of significant challenges for a constraint reasoning mechanism. In this paper, we introduce a general framework for handling dynamic constraint networks with real-valued variables, by using procedures to represent and effectively reason about general constraints. The framework is based on a sound theoretical foundation, and can be proven to be sound and complete under well-defined conditions. Furthermore, the framework provides hybrid reasoning capabilities, as alternative solution methods like mathematical programming can be incorporated into the framework, in the form of procedures.

  14. (non) Emergent Constraints

    NASA Astrophysics Data System (ADS)

    Jackson, C. S.; Hattab, M. W.; Huerta, G.

    2014-12-01

    Emergent constraints are observable quantities that provide some physical basis for testing or predicting how a climate model will respond to greenhouse gas forcing. Very few such constraints have been identified for the multi-model CMIP archive. Here we explore the question of whether constraints that apply to a single model, a perturbed parameter ensemble (PPE) of the Community Atmosphere Model (CAM3.1), can be applied to predicting the climate sensitivities of models within the CMIP archive. In particular we construct our predictive patterns from multivariate EOFs of the CAM3.1 ensemble control climate. Multiple regressive statistical models were created that do an excellent job of predicting CAM3.1 sensitivity to greenhouse gas forcing. However, these same patterns fail spectacularly to predict sensitivities of models within the CMIP archive. We attribute this failure to several factors. First, and perhaps the most important, is that the structures affecting climate sensitivity in CAM3.1 have a unique signature in the space of our multivariate EOF patterns that are unlike any other climate model. That is to say, we should not expect CAM3.1 to represent the way another models within CMIP archive respond to greenhouse gas forcing. The second, perhaps related, reason is that the CAM3.1 PPE does a poor job of spanning the range of climates and responses found within the CMIP archive. We shall discuss the implications of these results for the prospect of finding emergent constraints within the CMIP archive. We will also discuss what this may mean for establishing uncertainties in climate projections.

  15. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1991-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocations for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its applications to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  16. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1991-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint-based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all the inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocation for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its application to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  17. Constraint-based scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte

    1993-01-01

    The GERRY scheduling system developed by NASA Ames with assistance from the Lockheed Space Operations Company, and the Lockheed Artificial Intelligence Center, uses a method called constraint-based iterative repair. Using this technique, one encodes both hard rules and preference criteria into data structures called constraints. GERRY repeatedly attempts to improve schedules by seeking repairs for violated constraints. The system provides a general scheduling framework which is being tested on two NASA applications. The larger of the two is the Space Shuttle Ground Processing problem which entails the scheduling of all the inspection, repair, and maintenance tasks required to prepare the orbiter for flight. The other application involves power allocation for the NASA Ames wind tunnels. Here the system will be used to schedule wind tunnel tests with the goal of minimizing power costs. In this paper, we describe the GERRY system and its application to the Space Shuttle problem. We also speculate as to how the system would be used for manufacturing, transportation, and military problems.

  18. Discovery Guide.

    ERIC Educational Resources Information Center

    Edwards, Claudia

    This guide describes a project (Teamwork Approach to Better Schools) developed to promote the establishment of a formal teacher support network in a variety of schools within a local support district. The model is a guide to newcomers to the project, helping eliminate startup problems and providing a sound base of experiences. The program began…

  19. Structure Constraints in a Constraint-Based Planner

    NASA Technical Reports Server (NTRS)

    Pang, Wan-Lin; Golden, Keith

    2004-01-01

    In this paper we report our work on a new constraint domain, where variables can take structured values. Earth-science data processing (ESDP) is a planning domain that requires the ability to represent and reason about complex constraints over structured data, such as satellite images. This paper reports on a constraint-based planner for ESDP and similar domains. We discuss our approach for translating a planning problem into a constraint satisfaction problem (CSP) and for representing and reasoning about structured objects and constraints over structures.

  20. Genetic structure of Pilosocereus gounellei (Cactaceae) as revealed by AFLP marker to guide proposals for improvement and restoration of degraded areas in Caatinga biome.

    PubMed

    Monteiro, E R; Strioto, D K; Meirelles, A C S; Mangolin, C A; Machado, M F P S

    2015-12-15

    Amplified fragment length polymorphism (AFLP) analysis was used to evaluate DNA polymorphism in Pilosocereus gounellei with the aim of differentiating samples grown in different Brazilian semiarid regions. Seven primer pairs were used to amplify 703 AFLP markers, of which 700 (99.21%) markers were polymorphic. The percentage of polymorphic markers ranged from 95.3% for the primer combination E-AAG/M-CTT to 100% for E-ACC/M-CAT, E-ACC/M-CAA, E-AGC/M-CAG, E-ACT/M-CTA, and E-AGG/M-CTG. The largest number of informative markers (126) was detected using the primer combination E-AAC/M-CTA. Polymorphism of the amplified DNA fragments ranged from 72.55% (in sample from Piauí State) to 82.79% (in samples from Rio Grande Norte State), with an average of 75.39%. Despite the high genetic diversity of AFLP markers in xiquexique, analysis using the STRUCTURE software identified relatively homogeneous clusters of xiquexique from the same location, indicating a differentiation at the molecular level, among the plant samples from different regions of the Caatinga biome. The AFLP methodology identified genetically homogeneous and contrasting plants, as well as plants from different regions with common DNA markers. Seeds from such plants can be used for further propagation of plants for establishment of biodiversity conservation units and restoration of degraded areas of the Caatinga biome.

  1. Maximum Entropy Guide for BSS

    NASA Astrophysics Data System (ADS)

    Górriz, J. M.; Puntonet, C. G.; Medialdea, E. G.; Rojas, F.

    2005-11-01

    This paper proposes a novel method for Blindly Separating unobservable independent component (IC) Signals (BSS) based on the use of a maximum entropy guide (MEG). The paper also includes a formal proof on the convergence of the proposed algorithm using the guiding operator, a new concept in the genetic algorithm (GA) scenario. The Guiding GA (GGA) presented in this work, is able to extract IC with faster rate than the previous ICA algorithms, based on maximum entropy contrast functions, as input space dimension increases. It shows significant accuracy and robustness than the previous approaches in any case.

  2. GPU-enabled projectile guidance for impact area constraints

    NASA Astrophysics Data System (ADS)

    Rogers, Jonathan

    2013-05-01

    Guided projectile engagement scenarios often involve impact area constraints, in which it may be less desirable to incur miss distance on one side of a target or within a specified boundary near the target area. Current projectile guidance schemes such as impact point predictors cannot handle these constraints within the guidance loop, and may produce dispersion patterns that are insensitive to these constraints. In this paper, a new projectile guidance law is proposed that leverages real-time Monte Carlo impact point prediction to continually evaluate the probability of violating impact area constraints. The desired aim point is then adjusted accordingly. Real-time Monte Carlo simulation is enabled within the feedback loop through use of graphics processing units (GPU's), which provide parallel pipelines through which a dispersion pattern can routinely be predicted. The result is a guidance law that can achieve minimum miss distance while avoiding impact area constraints. The new guidance law is described and formulated as a nonlinear optimization problem which is solved in real-time through massively-parallel Monte Carlo simulation. An example simulation is shown in which impact area constraints are enforced and the methodology of stochastic guidance is demonstrated. Finally, Monte Carlo simulations are shown which demonstrate the ability of the stochastic guidance scheme to avoid an arbitrary set of impact area constraints, generating an impact probability density function that optimally trades miss distance within the restricted impact area. The proposed guidance scheme has applications beyond smart weapons to include missiles, UAV's, and other autonomous systems.

  3. Genetics Home Reference: infantile systemic hyalinosis

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions infantile systemic hyalinosis infantile systemic ...

  4. Genetics Home Reference: Rabson-Mendenhall syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Rabson-Mendenhall syndrome Rabson-Mendenhall ...

  5. Genetics Home Reference: microvillus inclusion disease

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions microvillus inclusion disease microvillus inclusion ...

  6. Genetics Home Reference: multiple pterygium syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions multiple pterygium syndrome multiple pterygium ...

  7. Genetics Home Reference: glutathione synthetase deficiency

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions glutathione synthetase deficiency glutathione synthetase ...

  8. Genetics Home Reference: X-linked agammaglobulinemia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions X-linked agammaglobulinemia X-linked ...

  9. Genetics Home Reference: Baraitser-Winter syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Baraitser-Winter syndrome Baraitser-Winter ...

  10. A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide treatment for postpartum pain and avert infant adverse events.

    PubMed

    Moretti, M E; Lato, D F; Berger, H; Koren, G; Ito, S; Ungar, W J

    2017-07-11

    Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.The Pharmacogenomics Journal advance online publication, 11 July 2017; doi:10.1038/tpj.2017.33.

  11. Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening.

    PubMed

    Morris, Lilah F; Waguespack, Steven G; Edeiken-Monroe, Beth S; Lee, Jeff E; Rich, Thereasa A; Ying, Anita K; Warneke, Carla L; Evans, Douglas B; Perrier, Nancy D; Grubbs, Elizabeth G

    2013-01-01

    American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal. We hypothesized that normal US would not exclude a final pathology diagnosis of medullary thyroid cancer (MTC). We retrospectively queried a MEN2A database for patients aged<18 years, diagnosed through genetic screening, who underwent preoperative US and thyroidectomy at our institution, comparing preoperative US and Ct results with pathologic findings. 35 eligible patients underwent surgery at median age of 6.3 (range 3.0-13.8) years. Mean MTC size was 2.9 (range 0.5-6.0) mm. The sensitivity of a US lesion≥5 mm in predicting MTC was 13% [95% confidence interval (CI) 2%, 40%], and the specificity was 95% [95% CI 75%, 100%]. Elevated Ct predicted MTC in 13/15 patients (sensitivity 87% [95% CI 60%, 98%], specificity 35% [95% CI 15%, 59%]). The area under the receiver operating characteristic curve (AUC) for using US lesion of any size to predict MTC was 0.50 [95% CI 0.33, 0.66], suggesting that US size has poor ability to discriminate MTC from non-MTC cases. The AUC for Ct level at 0.65 [95% CI 0.46, 0.85] was better than that of US but not age [AUC 0.62, 95% CI 0.42, 0.82]. In asymptomatic children with MEN2A diagnosed by genetic screening, preoperative thyroid US was not sensitive in identifying MTC of any size and, when determining the age for surgery, should not be used to predict microscopic MTC.

  12. Constraining neutron guide optimizations with phase-space considerations

    NASA Astrophysics Data System (ADS)

    Bertelsen, Mads; Lefmann, Kim

    2016-09-01

    We introduce a method named the Minimalist Principle that serves to reduce the parameter space for neutron guide optimization when the required beam divergence is limited. The reduced parameter space will restrict the optimization to guides with a minimal neutron intake that are still theoretically able to deliver the maximal possible performance. The geometrical constraints are derived using phase-space propagation from moderator to guide and from guide to sample, while assuming that the optimized guides will achieve perfect transport of the limited neutron intake. Guide systems optimized using these constraints are shown to provide performance close to guides optimized without any constraints, however the divergence received at the sample is limited to the desired interval, even when the neutron transport is not limited by the supermirrors used in the guide. As the constraints strongly limit the parameter space for the optimizer, two control parameters are introduced that can be used to adjust the selected subspace, effectively balancing between maximizing neutron transport and avoiding background from unnecessary neutrons. One parameter is needed to describe the expected focusing abilities of the guide to be optimized, going from perfectly focusing to no correlation between position and velocity. The second parameter controls neutron intake into the guide, so that one can select exactly how aggressively the background should be limited. We show examples of guides optimized using these constraints which demonstrates the higher signal to noise than conventional optimizations. Furthermore the parameter controlling neutron intake is explored which shows that the simulated optimal neutron intake is close to the analytically predicted, when assuming that the guide is dominated by multiple scattering events.

  13. Evolutionary constraints in high-dimensional trait sets.

    PubMed

    Hine, Emma; McGuigan, Katrina; Blows, Mark W

    2014-07-01

    Genetic variation for individual traits is typically abundant, but for some multivariate combinations it is very low, suggesting that evolutionary limits might be generated by the geometric distribution of genetic variance. To test this prediction, we artificially selected along all eight genetic eigenvectors of a set of eight quantitative traits in Drosophila serrata. After six generations of 50% truncation selection, at least one replicate population of all treatments responded to selection, allowing us to reject a null genetic subspace as a cause of evolutionary constraint in this system. However, while all three replicate populations of the first five selection treatments displayed a significant response, the remaining three, characterized by low genetic variance in their selection indexes in the base population, displayed inconsistent responses to selection. The observation that only four of the nine replicate populations evolved in response to the direct selection applied to them in these low genetic variance treatments, led us to conclude that a nearly null subspace did limit evolution. Dimensions associated with low genetic variance are often found in multivariate analyses of standing genetic variance in morphological traits, suggesting that the nearly null genetic subspace may be a common mechanism of evolutionary constraint in nature.

  14. Asteroseismic constraints for Gaia

    NASA Astrophysics Data System (ADS)

    Creevey, O. L.; Thévenin, F.

    2012-12-01

    Distances from the Gaia mission will no doubt improve our understanding of stellar physics by providing an excellent constraint on the luminosity of the star. However, it is also clear that high precision stellar properties from, for example, asteroseismology, will also provide a needed input constraint in order to calibrate the methods that Gaia will use, e.g. stellar models or GSP_Phot. For solar-like stars (F, G, K IV/V), asteroseismic data delivers at the least two very important quantities: (1) the average large frequency separation < Δ ν > and (2) the frequency corresponding to the maximum of the modulated-amplitude spectrum ν_{max}. Both of these quantities are related directly to stellar parameters (radius and mass) and in particular their combination (gravity and density). We show how the precision in < Δ ν >, ν_{max}, and atmospheric parameters T_{eff} and [Fe/H] affect the determination of gravity (log g) for a sample of well-known stars. We find that log g can be determined within less than 0.02 dex accuracy for our sample while considering precisions in the data expected for V˜12 stars from Kepler data. We also derive masses and radii which are accurate to within 1σ of the accepted values. This study validates the subsequent use of all of the available asteroseismic data on solar-like stars from the Kepler field (>500 IV/V stars) in order to provide a very important constraint for Gaia calibration of GSP_Phot} through the use of log g. We note that while we concentrate on IV/V stars, both the CoRoT and Kepler fields contain asteroseismic data on thousands of giant stars which will also provide useful calibration measures.

  15. Practical Cleanroom Operations Constraints

    NASA Technical Reports Server (NTRS)

    Hughes, David; Ginyard, Amani

    2007-01-01

    This viewgraph presentation reviews the GSFC Cleanroom Facility i.e., Spacecraft Systems Development and Integration Facility (SSDIF) with particular interest in its use during the development of the Wide Field Camera 3 (WFC3). The SSDIF is described and a diagram of the SSDIF is shown. A Constraint Table was created for consistency within Contamination Control Team. This table is shown. Another table that shows the activities that were allowed during the integration under given WFC3 condition and activity location is presented. Three decision trees are shown for different phases of the work: (1) Hardware Relocation, Hardware Work, and Contamination Control Operations.

  16. A novel constraint for thermodynamically designing DNA sequences.

    PubMed

    Zhang, Qiang; Wang, Bin; Wei, Xiaopeng; Zhou, Changjun

    2013-01-01

    Biotechnological and biomolecular advances have introduced novel uses for DNA such as DNA computing, storage, and encryption. For these applications, DNA sequence design requires maximal desired (and minimal undesired) hybridizations, which are the product of a single new DNA strand from 2 single DNA strands. Here, we propose a novel constraint to design DNA sequences based on thermodynamic properties. Existing constraints for DNA design are based on the Hamming distance, a constraint that does not address the thermodynamic properties of the DNA sequence. Using a unique, improved genetic algorithm, we designed DNA sequence sets which satisfy different distance constraints and employ a free energy gap based on a minimum free energy (MFE) to gauge DNA sequences based on set thermodynamic properties. When compared to the best constraints of the Hamming distance, our method yielded better thermodynamic qualities. We then used our improved genetic algorithm to obtain lower-bound DNA sequence sets. Here, we discuss the effects of novel constraint parameters on the free energy gap.

  17. Symbolic Constraint Maintenance Grid

    NASA Technical Reports Server (NTRS)

    James, Mark

    2006-01-01

    Version 3.1 of Symbolic Constraint Maintenance Grid (SCMG) is a software system that provides a general conceptual framework for utilizing pre-existing programming techniques to perform symbolic transformations of data. SCMG also provides a language (and an associated communication method and protocol) for representing constraints on the original non-symbolic data. SCMG provides a facility for exchanging information between numeric and symbolic components without knowing the details of the components themselves. In essence, it integrates symbolic software tools (for diagnosis, prognosis, and planning) with non-artificial-intelligence software. SCMG executes a process of symbolic summarization and monitoring of continuous time series data that are being abstractly represented as symbolic templates of information exchange. This summarization process enables such symbolic- reasoning computing systems as artificial- intelligence planning systems to evaluate the significance and effects of channels of data more efficiently than would otherwise be possible. As a result of the increased efficiency in representation, reasoning software can monitor more channels and is thus able to perform monitoring and control functions more effectively.

  18. Radiation shielding for neutron guides

    NASA Astrophysics Data System (ADS)

    Ersez, T.; Braoudakis, G.; Osborn, J. C.

    2006-11-01

    Models of the neutron guide shielding for the out of bunker guides on the thermal and cold neutron beam lines of the OPAL Reactor (ANSTO) were constructed using the Monte Carlo code MCNP 4B. The neutrons that were not reflected inside the guides but were absorbed by the supermirror (SM) layers were noted to be a significant source of gammas. Gammas also arise from neutrons absorbed by the B, Si, Na and K contained in the glass. The proposed shielding design has produced compact shielding assemblies. These arrangements are consistent with safety requirements, floor load limits, and cost constraints. To verify the design a prototype was assembled consisting of 120 mm thick Pb(96%)Sb(4%) walls resting on a concrete block. There was good agreement between experimental measurements and calculated dose rates for bulk shield regions.

  19. Are Africans, Europeans, and Asians Different “Races”? A Guided-Inquiry Lab for Introducing Undergraduate Students to Genetic Diversity and Preparing Them to Study Natural Selection

    PubMed Central

    Kalinowski, Steven T.; Andrews, Tessa M.; Leonard, Mary J.; Snodgrass, Meagan

    2012-01-01

    Many students do not recognize that individual organisms within populations vary, and this may make it difficult for them to recognize the essential role variation plays in natural selection. Also, many students have weak scientific reasoning skills, and this makes it difficult for them to recognize misconceptions they might have. This paper describes a 2-h laboratory for college students that introduces them to genetic diversity and gives them practice using hypothetico-deductive reasoning. In brief, the lab presents students with DNA sequences from Africans, Europeans, and Asians, and asks students to determine whether people from each continent qualify as distinct “races.” Comparison of the DNA sequences shows that people on each continent are not more similar to one another than to people on other continents, and therefore do not qualify as distinct races. Ninety-four percent of our students reported that the laboratory was interesting, and 79% reported that it was a valuable learning experience. We developed and used a survey to measure the extent to which students recognized variation and its significance within populations and showed that the lab increased student awareness of variation. We also showed that the lab improved the ability of students to construct hypothetico-deductive arguments. PMID:22665587

  20. Jasmonate signaling in the field, part II: insect-guided characterization of genetic variations in jasmonate-dependent defenses of transgenic and natural Nicotiana attenuata populations.

    PubMed

    Gaquerel, Emmanuel; Stitz, Michael; Kallenbach, Mario; Baldwin, Ian T

    2013-01-01

    The introduction of genetically modified plants into natural habitats represents a valuable means to determine organismic level functions of a gene and its effects on a plant's interaction with other organisms. Nicotiana attenuata, a wild tobacco species native of the southwestern USA that grows in the immediate postfire environment, is one of the important host plants for herbivore populations recolonizing recently burned habitats in the Great Basin Desert. Here, we provide detailed guidelines for the analysis, under field conditions, of jasmonate-dependent defense and its impact on the plant's native herbivore community. The procedures are based on the field release of transgenic lines silenced for jasmonate biogenesis, metabolism, or perception to conduct association studies between defense trait expression (secondary metabolite and trypsin proteinase inhibitor accumulation) and insect infestations. Additionally, because some insects have evolved mechanisms to "eavesdrop" on jasmonate signaling when selecting their host plants, we describe how leafhoppers of the species Empoasca, which selectively colonize jasmonate-deficient plants, can be used as "bloodhounds" for identifying natural variations in jasmonate signaling among natural N. attenuata populations.

  1. Toward a theory of constraints.

    PubMed

    Breunlin, D C

    1999-06-01

    Grounded in the cybernetic concept of negative explanation, the theory of constraints examines how human systems are kept from solving problems. To identify constraints, therapists must know where to look for them and what to look for. The theory proposes that constraints exist among the levels of a biopsychosocial system, which include biology, person, relationship, family, community, and society. The six metaframeworks of organization, sequences, mind, development, gender, and culture assist constraint identification. Combining the levels and metaframeworks creates a web of constraints, the complexity of which determines how difficult it will be to solve a given problem. The theory of constraint offers an integrative and pragmatic approach to therapy while simultaneously honoring the complexity of human systems.

  2. Relative constraints and evolution

    NASA Astrophysics Data System (ADS)

    Ochoa, Juan G. Diaz

    2014-03-01

    Several mathematical models of evolving systems assume that changes in the micro-states are constrained to the search of an optimal value in a local or global objective function. However, the concept of evolution requires a continuous change in the environment and species, making difficult the definition of absolute optimal values in objective functions. In this paper, we define constraints that are not absolute but relative to local micro-states, introducing a rupture in the invariance of the phase space of the system. This conceptual basis is useful to define alternative mathematical models for biological (or in general complex) evolving systems. We illustrate this concept with a modified Ising model, which can be useful to understand and model problems like the somatic evolution of cancer.

  3. Neural constraints on learning.

    PubMed

    Sadtler, Patrick T; Quick, Kristin M; Golub, Matthew D; Chase, Steven M; Ryu, Stephen I; Tyler-Kabara, Elizabeth C; Yu, Byron M; Batista, Aaron P

    2014-08-28

    Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain-computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain-computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already

  4. Neural constraints on learning

    PubMed Central

    Sadtler, Patrick T.; Quick, Kristin M.; Golub, Matthew D.; Chase, Steven M.; Ryu, Stephen I.; Tyler-Kabara, Elizabeth C.; Yu, Byron M.; Batista, Aaron P.

    2014-01-01

    Motor, sensory, and cognitive learning require networks of neurons to generate new activity patterns. Because some behaviors are easier to learn than others1,2, we wondered if some neural activity patterns are easier to generate than others. We asked whether the existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define the constraint. We employed a closed-loop intracortical brain-computer interface (BCI) learning paradigm in which Rhesus monkeys controlled a computer cursor by modulating neural activity patterns in primary motor cortex. Using the BCI paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. These patterns comprise a low-dimensional space (termed the intrinsic manifold, or IM) within the high-dimensional neural firing rate space. They presumably reflect constraints imposed by the underlying neural circuitry. We found that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the IM. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the IM. This result suggests that the existing structure of a network can shape learning. On the timescale of hours, it appears to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess3,4. PMID:25164754

  5. Comparative population genomics of the Borrelia burgdorferi species complex reveals high degree of genetic isolation among species and underscores benefits and constraints to studying intra-specific epidemiological processes.

    PubMed

    Jacquot, Maude; Gonnet, Mathieu; Ferquel, Elisabeth; Abrial, David; Claude, Alexandre; Gasqui, Patrick; Choumet, Valérie; Charras-Garrido, Myriam; Garnier, Martine; Faure, Benjamin; Sertour, Natacha; Dorr, Nelly; De Goër, Jocelyn; Vourc'h, Gwenaël; Bailly, Xavier

    2014-01-01

    Lyme borreliosis, one of the most frequently contracted zoonotic diseases in the Northern Hemisphere, is caused by bacteria belonging to different genetic groups within the Borrelia burgdorferi species complex, which are transmitted by ticks among various wildlife reservoirs, such as small mammals and birds. These features make the Borrelia burgdorferi species complex an attractive biological model that can be used to study the diversification and the epidemiology of endemic bacterial pathogens. We investigated the potential of population genomic approaches to study these processes. Sixty-three strains belonging to three species within the Borrelia burgdorferi complex were isolated from questing ticks in Alsace (France), a region where Lyme disease is highly endemic. We first aimed to characterize the degree of genetic isolation among the species sampled. Phylogenetic and coalescent-based analyses revealed clear delineations: there was a ∼50 fold difference between intra-specific and inter-specific recombination rates. We then investigated whether the population genomic data contained information of epidemiological relevance. In phylogenies inferred using most of the genome, conspecific strains did not cluster in clades. These results raise questions about the relevance of different strategies when investigating pathogen epidemiology. For instance, here, both classical analytic approaches and phylodynamic simulations suggested that population sizes and migration rates were higher in B. garinii populations, which are normally associated with birds, than in B. burgdorferi s.s. populations. The phylogenetic analyses of the infection-related ospC gene and its flanking region provided additional support for this finding. Traces of recombination among the B. burgdorferi s.s. lineages and lineages associated with small mammals were found, suggesting that they shared the same hosts. Altogether, these results provide baseline evidence that can be used to formulate

  6. Mitochondrial genetics

    PubMed Central

    Chinnery, Patrick Francis; Hudson, Gavin

    2013-01-01

    Introduction In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders. Sources of data In this article, a review of the current mitochondrial genetics literature was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (www.mitomap.org), the Human DNA polymerase Gamma Mutation Database (http://tools.niehs.nih.gov/polg/) and PhyloTree.org (www.phylotree.org), a repository of global mtDNA variation. Areas of agreement The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases. Areas of controversy The exact mechanisms which govern the inheritance of mtDNA are hotly debated. Growing points Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease. PMID:23704099

  7. Fixed Costs and Hours Constraints

    ERIC Educational Resources Information Center

    Johnson, William R.

    2011-01-01

    Hours constraints are typically identified by worker responses to questions asking whether they would prefer a job with more hours and more pay or fewer hours and less pay. Because jobs with different hours but the same rate of pay may be infeasible when there are fixed costs of employment or mandatory overtime premia, the constraint in those…

  8. Market segmentation using perceived constraints

    Treesearch

    Jinhee Jun; Gerard Kyle; Andrew Mowen

    2008-01-01

    We examined the practical utility of segmenting potential visitors to Cleveland Metroparks using their constraint profiles. Our analysis identified three segments based on their scores on the dimensions of constraints: Other priorities--visitors who scored the highest on 'other priorities' dimension; Highly Constrained--visitors who scored relatively high on...

  9. Thermodynamic Constraints Improve Metabolic Networks.

    PubMed

    Krumholz, Elias W; Libourel, Igor G L

    2017-08-08

    In pursuit of establishing a realistic metabolic phenotypic space, the reversibility of reactions is thermodynamically constrained in modern metabolic networks. The reversibility constraints follow from heuristic thermodynamic poise approximations that take anticipated cellular metabolite concentration ranges into account. Because constraints reduce the feasible space, draft metabolic network reconstructions may need more extensive reconciliation, and a larger number of genes may become essential. Notwithstanding ubiquitous application, the effect of reversibility constraints on the predictive capabilities of metabolic networks has not been investigated in detail. Instead, work has focused on the implementation and validation of the thermodynamic poise calculation itself. With the advance of fast linear programming-based network reconciliation, the effects of reversibility constraints on network reconciliation and gene essentiality predictions have become feasible and are the subject of this study. Networks with thermodynamically informed reversibility constraints outperformed gene essentiality predictions compared to networks that were constrained with randomly shuffled constraints. Unconstrained networks predicted gene essentiality as accurately as thermodynamically constrained networks, but predicted substantially fewer essential genes. Networks that were reconciled with sequence similarity data and strongly enforced reversibility constraints outperformed all other networks. We conclude that metabolic network analysis confirmed the validity of the thermodynamic constraints, and that thermodynamic poise information is actionable during network reconciliation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. On Constraints in Assembly Planning

    SciTech Connect

    Calton, T.L.; Jones, R.E.; Wilson, R.H.

    1998-12-17

    Constraints on assembly plans vary depending on product, assembly facility, assembly volume, and many other factors. Assembly costs and other measures to optimize vary just as widely. To be effective, computer-aided assembly planning systems must allow users to express the plan selection criteria that appIy to their products and production environments. We begin this article by surveying the types of user criteria, both constraints and quality measures, that have been accepted by assembly planning systems to date. The survey is organized along several dimensions, including strategic vs. tactical criteria; manufacturing requirements VS. requirements of the automated planning process itself and the information needed to assess compliance with each criterion. The latter strongly influences the efficiency of planning. We then focus on constraints. We describe a framework to support a wide variety of user constraints for intuitive and efficient assembly planning. Our framework expresses all constraints on a sequencing level, specifying orders and conditions on part mating operations in a number of ways. Constraints are implemented as simple procedures that either accept or reject assembly operations proposed by the planner. For efficiency, some constraints are supplemented with special-purpose modifications to the planner's algorithms. Fast replanning enables an interactive plan-view-constrain-replan cycle that aids in constraint discovery and documentation. We describe an implementation of the framework in a computer-aided assembly planning system and experiments applying the system to a number of complex assemblies, including one with 472 parts.

  11. Fixed Costs and Hours Constraints

    ERIC Educational Resources Information Center

    Johnson, William R.

    2011-01-01

    Hours constraints are typically identified by worker responses to questions asking whether they would prefer a job with more hours and more pay or fewer hours and less pay. Because jobs with different hours but the same rate of pay may be infeasible when there are fixed costs of employment or mandatory overtime premia, the constraint in those…

  12. Credit Constraints for Higher Education

    ERIC Educational Resources Information Center

    Solis, Alex

    2012-01-01

    This paper exploits a natural experiment that produces exogenous variation on credit access to determine the effect on college enrollment. The paper assess how important are credit constraints to explain the gap in college enrollment by family income, and what would be the gap if credit constraints are eliminated. Progress in college and dropout…

  13. Brain evolution and development: adaptation, allometry and constraint

    PubMed Central

    Barton, Robert A.

    2016-01-01

    Phenotypic traits are products of two processes: evolution and development. But how do these processes combine to produce integrated phenotypes? Comparative studies identify consistent patterns of covariation, or allometries, between brain and body size, and between brain components, indicating the presence of significant constraints limiting independent evolution of separate parts. These constraints are poorly understood, but in principle could be either developmental or functional. The developmental constraints hypothesis suggests that individual components (brain and body size, or individual brain components) tend to evolve together because natural selection operates on relatively simple developmental mechanisms that affect the growth of all parts in a concerted manner. The functional constraints hypothesis suggests that correlated change reflects the action of selection on distributed functional systems connecting the different sub-components, predicting more complex patterns of mosaic change at the level of the functional systems and more complex genetic and developmental mechanisms. These hypotheses are not mutually exclusive but make different predictions. We review recent genetic and neurodevelopmental evidence, concluding that functional rather than developmental constraints are the main cause of the observed patterns. PMID:27629025

  14. Homebuyer's Guide.

    ERIC Educational Resources Information Center

    Sindt, Roger P.; Harris, Jack

    Designed to assist prospective buyers in making such important decisions as whether to buy a new or older home and within what price range, the guide provides information on the purchase process. Discussion of the purchase process covers the life-cycle costs (recurring homeownership costs that must be met every month); selection of a home;…

  15. Persuasion Guide.

    ERIC Educational Resources Information Center

    1971

    In this teacher's guide to the textbook called "Persuasion" the emphasis is on assisting the teacher to develop in his students the skills of critical and creative thinking. Each instructional unit moves from the experience of persuasive techniques, through critical analysis, to the creative practice of the technique in question. Essays on…

  16. Teachers Guide.

    ERIC Educational Resources Information Center

    Linsky, Ronald B.; Schnitger, Ronald L.

    This guide provides teachers with copies of the materials given to students participating in the oceanography program of the Orange County Floating Laboratory Program and provides information concerning colleges and universities offering courses in oceanography and marine science, source of films, and sources of publications concerning the Navy's…

  17. Homebuyer's Guide.

    ERIC Educational Resources Information Center

    Sindt, Roger P.; Harris, Jack

    Designed to assist prospective buyers in making such important decisions as whether to buy a new or older home and within what price range, the guide provides information on the purchase process. Discussion of the purchase process covers the life-cycle costs (recurring homeownership costs that must be met every month); selection of a home;…

  18. Teachers Guide.

    ERIC Educational Resources Information Center

    Linsky, Ronald B.; Schnitger, Ronald L.

    This guide provides teachers with copies of the materials given to students participating in the oceanography program of the Orange County Floating Laboratory Program and provides information concerning colleges and universities offering courses in oceanography and marine science, source of films, and sources of publications concerning the Navy's…

  19. Interview Guide.

    ERIC Educational Resources Information Center

    Detroit Public Schools, MI.

    The questions in this interview guide pertain to the Detroit Public Schools Uniform Code of Student Conduct and City Wide Attendance Regulations. They are directed to school principals and assistant principals. The questions help to determine if the Uniform Code and Attendance Regulations were disseminated, if orientations were carried out, and…

  20. Instructor Guide.

    ERIC Educational Resources Information Center

    Langer, Philip; Borg, Walter R.

    This Instructor Guide is designed to acquaint the teacher educator with the Utah State University Protocol Project training materials. It deals with the protocol materials generally and with each module specifically, including the following: (a) an introduction to, and rationale for protocol modules; (b) ways of identifying specific kinds of…

  1. Generalizing Atoms in Constraint Logic

    NASA Technical Reports Server (NTRS)

    Page, C. David, Jr.; Frisch, Alan M.

    1991-01-01

    This paper studies the generalization of atomic formulas, or atoms, that are augmented with constraints on or among their terms. The atoms may also be viewed as definite clauses whose antecedents express the constraints. Atoms are generalized relative to a body of background information about the constraints. This paper first examines generalization of atoms with only monadic constraints. The paper develops an algorithm for the generalization task and discusses algorithm complexity. It then extends the algorithm to apply to atoms with constraints of arbitrary arity. The paper also presents semantic properties of the generalizations computed by the algorithms, making the algorithms applicable to such problems as abduction, induction, and knowledge base verification. The paper emphasizes the application to induction and presents a pac-learning result for constrained atoms.

  2. Genetic Counseling

    MedlinePlus

    ... Home > Pregnancy > Before or between pregnancies > Genetic counseling Genetic counseling E-mail to a friend Please fill ... a genetic counselor in your area. What is genetic counseling? Genetic counseling helps you understand how genes , ...

  3. A Hybrid Constraint Representation and Reasoning Framework

    NASA Technical Reports Server (NTRS)

    Golden, Keith; Pang, Wan-Lin

    2003-01-01

    This paper introduces JNET, a novel constraint representation and reasoning framework that supports procedural constraints and constraint attachments, providing a flexible way of integrating the constraint reasoner with a run- time software environment. Attachments in JNET are constraints over arbitrary Java objects, which are defined using Java code, at runtime, with no changes to the JNET source code.

  4. Infrared Kuiper Belt Constraints

    SciTech Connect

    Teplitz, V.L.; Stern, S.A.; Anderson, J.D.; Rosenbaum, D.; Scalise, R.J.; Wentzler, P.

    1999-05-01

    We compute the temperature and IR signal of particles of radius {ital a} and albedo {alpha} at heliocentric distance {ital R}, taking into account the emissivity effect, and give an interpolating formula for the result. We compare with analyses of {ital COBE} DIRBE data by others (including recent detection of the cosmic IR background) for various values of heliocentric distance {ital R}, particle radius {ital a}, and particle albedo {alpha}. We then apply these results to a recently developed picture of the Kuiper belt as a two-sector disk with a nearby, low-density sector (40{lt}R{lt}50{endash}90 AU) and a more distant sector with a higher density. We consider the case in which passage through a molecular cloud essentially cleans the solar system of dust. We apply a simple model of dust production by comet collisions and removal by the Poynting-Robertson effect to find limits on total and dust masses in the near and far sectors as a function of time since such a passage. Finally, we compare Kuiper belt IR spectra for various parameter values. Results of this work include: (1) numerical limits on Kuiper belt dust as a function of ({ital R}, {ital a}, {alpha}) on the basis of four alternative sets of constraints, including those following from recent discovery of the cosmic IR background by Hauser et al.; (2) application to the two-sector Kuiper belt model, finding mass limits and spectrum shape for different values of relevant parameters including dependence on time elapsed since last passage through a molecular cloud cleared the outer solar system of dust; and (3) potential use of spectral information to determine time since last passage of the Sun through a giant molecular cloud. {copyright} {ital {copyright} 1999.} {ital The American Astronomical Society}

  5. Evolutionary constraints or opportunities?

    PubMed Central

    Sharov, Alexei A.

    2014-01-01

    Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term “constraint” has negative connotations, I use the term “regulated variation” to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch “on” or “off” preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). PMID:24769155

  6. Resource allocation using constraint propagation

    NASA Technical Reports Server (NTRS)

    Rogers, John S.

    1990-01-01

    The concept of constraint propagation was discussed. Performance increases are possible with careful application of these constraint mechanisms. The degree of performance increase is related to the interdependence of the different activities resource usage. Although this method of applying constraints to activities and resources is often beneficial, it is obvious that this is no panacea cure for the computational woes that are experienced by dynamic resource allocation and scheduling problems. A combined effort for execution optimization in all areas of the system during development and the selection of the appropriate development environment is still the best method of producing an efficient system.

  7. Weighted constraints in generative linguistics.

    PubMed

    Pater, Joe

    2009-08-01

    Harmonic Grammar (HG) and Optimality Theory (OT) are closely related formal frameworks for the study of language. In both, the structure of a given language is determined by the relative strengths of a set of constraints. They differ in how these strengths are represented: as numerical weights (HG) or as ranks (OT). Weighted constraints have advantages for the construction of accounts of language learning and other cognitive processes, partly because they allow for the adaptation of connectionist and statistical models. HG has been little studied in generative linguistics, however, largely due to influential claims that weighted constraints make incorrect predictions about the typology of natural languages, predictions that are not shared by the more popular OT. This paper makes the case that HG is in fact a promising framework for typological research, and reviews and extends the existing arguments for weighted over ranked constraints.

  8. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist.

  9. Selective constraint on noncoding regions of hominid genomes.

    PubMed

    Bush, Eliot C; Lahn, Bruce T

    2005-12-01

    An important challenge for human evolutionary biology is to understand the genetic basis of human-chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

  10. Thermodynamic constraints for biochemical networks.

    PubMed

    Beard, Daniel A; Babson, Eric; Curtis, Edward; Qian, Hong

    2004-06-07

    The constraint-based approach to analysis of biochemical systems has emerged as a useful tool for rational metabolic engineering. Flux balance analysis (FBA) is based on the constraint of mass conservation; energy balance analysis (EBA) is based on non-equilibrium thermodynamics. The power of these approaches lies in the fact that the constraints are based on physical laws, and do not make use of unknown parameters. Here, we show that the network structure (i.e. the stoichiometric matrix) alone provides a system of constraints on the fluxes in a biochemical network which are feasible according to both mass balance and the laws of thermodynamics. A realistic example shows that these constraints can be sufficient for deriving unambiguous, biologically meaningful results. The thermodynamic constraints are obtained by comparing of the sign pattern of the flux vector to the sign patterns of the cycles of the internal cycle space via connection between stoichiometric network theory (SNT) and the mathematical theory of oriented matroids.

  11. Foundations of support constraint machines.

    PubMed

    Gnecco, Giorgio; Gori, Marco; Melacci, Stefano; Sanguineti, Marcello

    2015-02-01

    The mathematical foundations of a new theory for the design of intelligent agents are presented. The proposed learning paradigm is centered around the concept of constraint, representing the interactions with the environment, and the parsimony principle. The classical regularization framework of kernel machines is naturally extended to the case in which the agents interact with a richer environment, where abstract granules of knowledge, compactly described by different linguistic formalisms, can be translated into the unified notion of constraint for defining the hypothesis set. Constrained variational calculus is exploited to derive general representation theorems that provide a description of the optimal body of the agent (i.e., the functional structure of the optimal solution to the learning problem), which is the basis for devising new learning algorithms. We show that regardless of the kind of constraints, the optimal body of the agent is a support constraint machine (SCM) based on representer theorems that extend classical results for kernel machines and provide new representations. In a sense, the expressiveness of constraints yields a semantic-based regularization theory, which strongly restricts the hypothesis set of classical regularization. Some guidelines to unify continuous and discrete computational mechanisms are given so as to accommodate in the same framework various kinds of stimuli, for example, supervised examples and logic predicates. The proposed view of learning from constraints incorporates classical learning from examples and extends naturally to the case in which the examples are subsets of the input space, which is related to learning propositional logic clauses.

  12. Domestication changes innate constraints for birdsong learning.

    PubMed

    Kagawa, Hiroko; Suzuki, Kenta; Takahasi, Miki; Okanoya, Kazuo

    2014-07-01

    Birdsongs are acquired by imitating the sounds produced by conspecifics. Within a species, songs diverge by cultural transmission, but the range of species-specific features is restricted by innate constraints. Bengalese finches (Lonchura striata var. domestica) are a domesticated strain of the wild White-rumped munia (Lonchura striata). The songs of the domesticated strain have more tonal sounds and more variable sequences than those of the wild strain. We compared the features of songs that were produced by normal birds, isolation-reared birds, and cross-fostered birds in both White-rumped munias and Bengalese finches to identify differences in the genetic and environmental factors of their songs. Factor analyses were conducted based on 17 song measurements. We found that isolated songs differed from normal and cross-fostered songs, especially in unstable prosodic features. In addition, there were significant differences in sound property of mean frequency between the two strains regardless of the rearing conditions. Thus, innate constraints that partially determine birdsong phenotypes may be altered through domestication.

  13. Using Public-Private Partnerships to Mitigate Disparities in Access to Genetic Services: Lessons from Wisconsin.

    PubMed

    Senier, Laura; Kearney, Matthew; Orne, Jason

    This mixed-methods study reports on an outreach clinics program designed to deliver genetic services to medically underserved communities in Wisconsin. We show the geographic distribution, funding patterns, and utilization trends for outreach clinics over a 20-year period. Interviews with program planners and outreach clinic staff show how external and internal constraints limited the program's capacity. We compare clinic operations to the conceptual models guiding program design. Our findings show that state health officials had to scale back financial support for outreach clinic activities while healthcare providers faced increasing pressure from administrators to reduce investments in charity care. These external and internal constraints led to a decline in the overall number of patients served. We also find that redistribution of clinics to the Milwaukee area increased utilization among Hispanics but not among African-Americans. Our interviews suggest that these patterns may be a function of shortcomings embedded in the planning models. Planning models have three shortcomings. First, they do not identify the mitigation of health disparities as a specific goal. Second, they fail to acknowledge that partners face escalating profit-seeking mandates that may limit their capacity to provide charity services. Finally, they underemphasize the importance of seeking trusted partners, especially in working with communities that have been historically marginalized. There has been little discussion about equitably leveraging genetic advances that improve healthcare quality and efficacy. The role of State Health Agencies in mitigating disparities in access to genetic services has been largely ignored in the sociological literature.

  14. A Stochastic Approach to Diffeomorphic Point Set Registration with Landmark Constraints.

    PubMed

    Kolesov, Ivan; Lee, Jehoon; Sharp, Gregory; Vela, Patricio; Tannenbaum, Allen

    2016-02-01

    This work presents a deformable point set registration algorithm that seeks an optimal set of radial basis functions to describe the registration. A novel, global optimization approach is introduced composed of simulated annealing with a particle filter based generator function to perform the registration. It is shown how constraints can be incorporated into this framework. A constraint on the deformation is enforced whose role is to ensure physically meaningful fields (i.e., invertible). Further, examples in which landmark constraints serve to guide the registration are shown. Results on 2D and 3D data demonstrate the algorithm's robustness to noise and missing information.

  15. A Stochastic Approach to Diffeomorphic Point Set Registration With Landmark Constraints

    PubMed Central

    Kolesov, Ivan; Lee, Jehoon; Sharp, Gregory; Vela, Patricio; Tannenbaum, Allen

    2016-01-01

    This work presents a deformable point set registration algorithm that seeks an optimal set of radial basis functions to describe the registration. A novel, global optimization approach is introduced composed of simulated annealing with a particle filter based generator function to perform the registration. It is shown how constraints can be incorporated into this framework. A constraint on the deformation is enforced whose role is to ensure physically meaningful fields (i.e., invertible). Further, examples in which landmark constraints serve to guide the registration are shown. Results on 2D and 3D data demonstrate the algorithm’s robustness to noise and missing information. PMID:26761731

  16. Accessibility, constraint, and repetition in adaptive floral evolution.

    PubMed

    Wessinger, Carolyn A; Hileman, Lena C

    2016-11-01

    Adaptive phenotypic evolution is shaped by natural selection on multiple organismal traits as well as by genetic correlations among traits. Genetic correlations can arise through pleiotropy and can bias the production of phenotypic variation to certain combinations of traits. This phenomenon is referred to as developmental bias or constraint. Developmental bias may accelerate or constrain phenotypic evolution, depending on whether selection acts parallel or in opposition to genetic correlations among traits. We discuss examples from floral evolution where genetic correlations among floral traits contribute to rapid, coordinated evolution in multiple floral organ phenotypes and suggest future research directions that will explore the relationship between the genetic basis of adaptation and the pre-existing structure of genetic correlations. On the other hand, natural selection may act perpendicular to a strong genetic correlation, for example when two traits are encoded by a subset of the same genes and natural selection favors change in one trait and stability in the second trait. In such cases, adaptation is constrained by the availability of genetic variation that can influence the focal trait with minimal pleiotropic effects. Examples from plant diversification suggest that the origin of certain adaptations depends on the prior evolution of a gene copy with reduced pleiotropic effects, generated through the process of gene duplication followed by subfunctionalization or neofunctionalization. A history of gene duplication in some developmental pathways appears to have allowed particular flowering plant linages to have repeatedly evolved adaptations that might otherwise have been developmentally constrained. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Genetics Home Reference: 3-methylglutaconyl-CoA hydratase deficiency

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions 3-methylglutaconyl-CoA hydratase deficiency ...

  18. Genetics Home Reference: uromodulin-associated kidney disease

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions uromodulin-associated kidney disease uromodulin- ...

  19. Genetics Home Reference: scalp-ear-nipple syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions scalp-ear-nipple syndrome scalp- ...

  20. Genetics Home Reference: autosomal dominant hyper-IgE syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions autosomal dominant hyper-IgE syndrome ...

  1. Genetics Home Reference: thiamine-responsive megaloblastic anemia syndrome

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions thiamine-responsive megaloblastic anemia syndrome ...

  2. Genetics Home Reference: VLDLR-associated cerebellar hypoplasia

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions VLDLR-associated cerebellar hypoplasia VLDLR- ...

  3. Genetics Home Reference: DOLK-congenital disorder of glycosylation

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions DOLK-CDG DOLK-congenital disorder ...

  4. Developmental constraints on behavioural flexibility

    PubMed Central

    Holekamp, Kay E.; Swanson, Eli M.; Van Meter, Page E.

    2013-01-01

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility. PMID:23569298

  5. Developmental constraints on behavioural flexibility.

    PubMed

    Holekamp, Kay E; Swanson, Eli M; Van Meter, Page E

    2013-05-19

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.

  6. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  7. Science: Kindergarten. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  8. The transmission interface constraint problem

    SciTech Connect

    Baldick, R.; Kahn, E.

    1993-10-01

    Electric power transmission systems exhibit a number of complex constraints on their operation and usage. When a network is subject to a constraint that limits the amount of power that can be moved from one region to another, there is said to be an interface limit. The power systems literature gives no general treatment of the engineering-economics of this ubiquitous phenomenon. Particular aspects of interface limits are typically discussed in sophisticated technical detail, but the general engineering-economic trade-offs involved in relieving interface constraints have not been systematically addressed. We approach this problem in the spirit of a heuristic model. Such models are quite valuable under current industry conditions because they delineate technical opportunities and choices in situations where there may be conflicting views among competing parties and regulatory authorities. We organize and enumerate the choices, clarify the practical conditions that dictate the optimum in particular cases, and help to motivate the final choices made by planners.

  9. Symmetry constraint for foreground extraction.

    PubMed

    Fu, Huazhu; Cao, Xiaochun; Tu, Zhuowen; Lin, Dongdai

    2014-05-01

    Symmetry as an intrinsic shape property is often observed in natural objects. In this paper, we discuss how explicitly taking into account the symmetry constraint can enhance the quality of foreground object extraction. In our method, a symmetry foreground map is used to represent the symmetry structure of the image, which includes the symmetry matching magnitude and the foreground location prior. Then, the symmetry constraint model is built by introducing this symmetry structure into the graph-based segmentation function. Finally, the segmentation result is obtained via graph cuts. Our method encourages objects with symmetric parts to be consistently extracted. Moreover, our symmetry constraint model is applicable to weak symmetric objects under the part-based framework. Quantitative and qualitative experimental results on benchmark datasets demonstrate the advantages of our approach in extracting the foreground. Our method also shows improved results in segmenting objects with weak, complex symmetry properties.

  10. Magnetotail dynamics under isobaric constraints

    NASA Technical Reports Server (NTRS)

    Birn, Joachim; Schindler, Karl; Janicke, Lutz; Hesse, Michael

    1994-01-01

    Using linear theory and nonlinear MHD simulations, we investigate the resistive and ideal MHD stability of two-dimensional plasma configurations under the isobaric constraint dP/dt = 0, which in ideal MHD is equivalent to conserving the pressure function P = P(A), where A denotes the magnetic flux. This constraint is satisfied for incompressible modes, such as Alfven waves, and for systems undergoing energy losses. The linear stability analysis leads to a Schroedinger equation, which can be investigated by standard quantum mechanics procedures. We present an application to a typical stretched magnetotail configuration. For a one-dimensional sheet equilibrium characteristic properties of tearing instability are rediscovered. However, the maximum growth rate scales with the 1/7 power of the resistivity, which implies much faster growth than for the standard tearing mode (assuming that the resistivity is small). The same basic eigen-mode is found also for weakly two-dimensional equilibria, even in the ideal MHD limit. In this case the growth rate scales with the 1/4 power of the normal magnetic field. The results of the linear stability analysis are confirmed qualitatively by nonlinear dynamic MHD simulations. These results suggest the interesting possibility that substorm onset, or the thinning in the late growth phase, is caused by the release of a thermodynamic constraint without the (immediate) necessity of releasing the ideal MHD constraint. In the nonlinear regime the resistive and ideal developments differ in that the ideal mode does not lead to neutral line formation without the further release of the ideal MHD constraint; instead a thin current sheet forms. The isobaric constraint is critically discussed. Under perhaps more realistic adiabatic conditions the ideal mode appears to be stable but could be driven by external perturbations and thus generate the thin current sheet in the late growth phase, before a nonideal instability sets in.

  11. Greenstone belt tectonics: Thermal constraints

    NASA Technical Reports Server (NTRS)

    Bickle, M. J.; Nisbet, E. G.

    1986-01-01

    Archaean rocks provide a record of the early stages of planetary evolution. The interpretation is frustrated by the probable unrepresentative nature of the preserved crust and by the well known ambiguities of tectonic geological synthesis. Broad constraints can be placed on the tectonic processes in the early Earth from global scale modeling of thermal and chemical evolution of the Earth and its hydrosphere and atmosphere. The Archean record is the main test of such models. Available general model constraints are outlined based on the global tectonic setting within which Archaean crust evolved and on the direct evidence the Archaean record provides, particularly the thermal state of the early Earth.

  12. Life-history strategy determines constraints on immune function.

    PubMed

    Parker, Benjamin J; Barribeau, Seth M; Laughton, Alice M; Griffin, Lynn H; Gerardo, Nicole M

    2017-05-01

    Determining the factors governing investment in immunity is critical to understanding host-pathogen ecological and evolutionary dynamics. Studies often consider disease resistance in the context of life-history theory, with the expectation that investment in immunity will be optimized in anticipation of disease risk. Immunity, however, is constrained by context-dependent fitness costs. How the costs of immunity vary across life-history strategies has yet to be considered. Pea aphids are typically unwinged but produce winged offspring in response to high population densities and deteriorating conditions. This is an example of polyphenism, a strategy used by many organisms to adjust to environmental cues. The goal of this study was to examine the relationship between the fitness costs of immunity, pathogen resistance and the strength of an immune response across aphid morphs that differ in life-history strategy but are genetically identical. We measured fecundity of winged and unwinged aphids challenged with a heat-inactivated fungal pathogen, and found that immune costs are limited to winged aphids. We hypothesized that these costs reflect stronger investment in immunity in anticipation of higher disease risk, and that winged aphids would be more resistant due to a stronger immune response. However, producing wings is energetically expensive. This guided an alternative hypothesis - that investing resources into wings could lead to a reduced capacity to resist infection. We measured survival and pathogen load after live fungal infection, and we characterized the aphid immune response to fungi by measuring immune cell concentration and gene expression. We found that winged aphids are less resistant and mount a weaker immune response than unwinged aphids, demonstrating that winged aphids pay higher costs for a less effective immune response. Our results show that polyphenism is an understudied factor influencing the expression of immune costs. More generally, our work

  13. Genetics and the unity of biology. Program

    SciTech Connect

    Not Available

    1988-12-31

    International Congresses of Genetics, convened just once every five years, provide a rare opportunity for overview in the field of genetic engineering. The Congress, held August 20-27, 1988 in Toronto, Canada focused on the theme Genetics and the Unity of Biology, which was chosen because the concepts of modern genetics have provided biology with a unifying theoretical structure. This program guide contains a schedule of all Congress activities and a listing of all Symposia, Workshops and Poster Sessions held.

  14. Constraints in Implementation of HIV and AIDS Curriculum Integration in Primary Schools in Bungoma County, Kenya

    ERIC Educational Resources Information Center

    Mbach, Florence; Oboka, Wycliffe; Simiyu, Ruth; Wakhungu, Jacob

    2016-01-01

    Education was identified as the critical means of achieving behaviour change in and out of the classroom in order to prevent and mitigate the spread of HIV and AIDS among the youth. This study sought to investigate the constraints during HIV and AIDS curriculum implementation, the study was guided by social cognitive approach theories, survey and…

  15. Constraints on water use efficiency of drought tolerant maize grown in a semi-arid environment

    USDA-ARS?s Scientific Manuscript database

    Identifying the constraints on crop water use efficiency (WUE) will help develop strategies to mitigate these limitations, potentially guiding agronomic and irrigation management strategies as well as providing needed directions in breeding. Boundary functions identify the upper limits of yield per...

  16. A Model To Address Design Constraints of Training Delivered via Satellite. Study Number Eight.

    ERIC Educational Resources Information Center

    Montler, Joseph; Geroy, Gary D.

    This document: summarizes how some companies are addressing the design constraints involved in using satellite technology to deliver training, presents a model aimed at examining cost effectiveness of the satellite option, and includes a guide to designing instructional materials for delivery by satellite. A survey of 39 organizations, 12…

  17. A Model To Address Design Constraints of Training Delivered via Satellite. Study Number Eight.

    ERIC Educational Resources Information Center

    Montler, Joseph; Geroy, Gary D.

    This document: summarizes how some companies are addressing the design constraints involved in using satellite technology to deliver training, presents a model aimed at examining cost effectiveness of the satellite option, and includes a guide to designing instructional materials for delivery by satellite. A survey of 39 organizations, 12…

  18. Does justice require genetic enhancements?

    PubMed

    Holtug, N

    1999-04-01

    It is argued that justice in some cases provides a pro tanto reason genetically to enhance victims of the genetic lottery. Various arguments--both to the effect that justice provides no such reason and to the effect that while there may be such reasons, they are overridden by certain moral constraints--are considered and rejected. Finally, it is argued that justice provides stronger reasons to perform more traditional medical tasks (treatments), and that therefore genetic enhancements should not play an important role in a public health care system.

  19. Constraint elimination in dynamical systems

    NASA Technical Reports Server (NTRS)

    Singh, R. P.; Likins, P. W.

    1989-01-01

    Large space structures (LSSs) and other dynamical systems of current interest are often extremely complex assemblies of rigid and flexible bodies subjected to kinematical constraints. A formulation is presented for the governing equations of constrained multibody systems via the application of singular value decomposition (SVD). The resulting equations of motion are shown to be of minimum dimension.

  20. Constraint-Based Scheduling System

    NASA Technical Reports Server (NTRS)

    Zweben, Monte; Eskey, Megan; Stock, Todd; Taylor, Will; Kanefsky, Bob; Drascher, Ellen; Deale, Michael; Daun, Brian; Davis, Gene

    1995-01-01

    Report describes continuing development of software for constraint-based scheduling system implemented eventually on massively parallel computer. Based on machine learning as means of improving scheduling. Designed to learn when to change search strategy by analyzing search progress and learning general conditions under which resource bottleneck occurs.

  1. Financial Constraints: Explaining Your Position.

    ERIC Educational Resources Information Center

    Cargill, Jennifer

    1988-01-01

    Discusses the importance of educating library patrons about the library's finances and the impact of budget constraints and the escalating cost of serials on materials acquisition. Steps that can be taken in educating patrons by interpreting and publicizing financial information are suggested. (MES)

  2. Temporal Constraint Reasoning With Preferences

    NASA Technical Reports Server (NTRS)

    Khatib, Lina; Morris, Paul; Morris, Robert; Rossi, Francesca

    2001-01-01

    A number of reasoning problems involving the manipulation of temporal information can naturally be viewed as implicitly inducing an ordering of potential local decisions involving time (specifically, associated with durations or orderings of events) on the basis of preferences. For example. a pair of events might be constrained to occur in a certain order, and, in addition. it might be preferable that the delay between them be as large, or as small, as possible. This paper explores problems in which a set of temporal constraints is specified, where each constraint is associated with preference criteria for making local decisions about the events involved in the constraint, and a reasoner must infer a complete solution to the problem such that, to the extent possible, these local preferences are met in the best way. A constraint framework for reasoning about time is generalized to allow for preferences over event distances and durations, and we study the complexity of solving problems in the resulting formalism. It is shown that while in general such problems are NP-hard, some restrictions on the shape of the preference functions, and on the structure of the preference set, can be enforced to achieve tractability. In these cases, a simple generalization of a single-source shortest path algorithm can be used to compute a globally preferred solution in polynomial time.

  3. Continuous Optimization on Constraint Manifolds

    NASA Technical Reports Server (NTRS)

    Dean, Edwin B.

    1988-01-01

    This paper demonstrates continuous optimization on the differentiable manifold formed by continuous constraint functions. The first order tensor geodesic differential equation is solved on the manifold in both numerical and closed analytic form for simple nonlinear programs. Advantages and disadvantages with respect to conventional optimization techniques are discussed.

  4. Constraints on galaxy formation theories

    NASA Technical Reports Server (NTRS)

    Szalay, A. S.

    1986-01-01

    The present theories of galaxy formation are reviewed. The relation between peculiar velocities, temperature fluctuations of the microwave background and the correlation function of galaxies point to the possibility that galaxies do not form uniformly everywhere. The velocity data provide strong constraints on the theories even in the case when light does not follow mass of the universe.

  5. Institutional constraints on alternative water for energy: a guidebook for regional assessments

    SciTech Connect

    Not Available

    1980-11-01

    Basic information is presented about the legal, political, and social constraints faced by energy developers in the acquisition of water from underground, irrigation return flow, municipal waste, and saline sources. It is a guide to those institutional constraints which are general and pronounced enough to be important for regional assessments. First, attention was focused on the acquisition phase of the water use cycle. Second, constraints were analyzed primarily from a regional, rather than state-by-state, perspective. Emphasis was placed generally on the West - particularly the synfuel-rich Rocky Mountain states, the East, and Mid-West, in that order. Alaska and Hawaii were not surveyed. Third, the study focuses on the constraints associated with groundwater, municipal waste, irrigation return flow, and sea water, in that order. The phrase, institutional constraints, as used in the study, means legal, social, economic, and political restrictions, requirements, circumstances, or conditions that must be anticipated or responded to in order to acquire water for energy development. The study focuses primarily on legal constraints and secondarily on political constraints, because they tend to encompass or reflect other forms of institutional constraints.

  6. COATING ALTERNATIVES GUIDE (CAGE) USER'S GUIDE

    EPA Science Inventory

    The guide provides instructions for using the Coating Alternatives GuidE (CAGE) software program, version 1.0. It assumes that the user is familiar with the fundamentals of operating an IBM-compatible personal computer (PC) under the Microsoft disk operating system (MS-DOS). CAGE...

  7. COATING ALTERNATIVES GUIDE (CAGE) USER'S GUIDE

    EPA Science Inventory

    The guide provides instructions for using the Coating Alternatives GuidE (CAGE) software program, version 1.0. It assumes that the user is familiar with the fundamentals of operating an IBM-compatible personal computer (PC) under the Microsoft disk operating system (MS-DOS). CAGE...

  8. Protective Action Guides (PAGs)

    EPA Pesticide Factsheets

    The Protective Action Guide (PAG) manual contains radiation dose guidelines that would trigger public safety measures. EPA developed Protective Action Guides to help responders plan for radiation emergencies.

  9. Mathematical Constraints on FST: Biallelic Markers in Arbitrarily Many Populations.

    PubMed

    Alcala, Nicolas; Rosenberg, Noah A

    2017-07-01

    [Formula: see text] is one of the most widely used statistics in population genetics. Recent mathematical studies have identified constraints that challenge interpretations of [Formula: see text] as a measure with potential to range from 0 for genetically similar populations to 1 for divergent populations. We generalize results obtained for population pairs to arbitrarily many populations, characterizing the mathematical relationship between [Formula: see text] the frequency M of the more frequent allele at a polymorphic biallelic marker, and the number of subpopulations K We show that for fixed K, [Formula: see text] has a peculiar constraint as a function of M, with a maximum of 1 only if [Formula: see text] for integers i with [Formula: see text] For fixed M, as K grows large, the range of [Formula: see text] becomes the closed or half-open unit interval. For fixed K, however, some [Formula: see text] always exists at which the upper bound on [Formula: see text] lies below [Formula: see text] We use coalescent simulations to show that under weak migration, [Formula: see text] depends strongly on M when K is small, but not when K is large. Finally, examining data on human genetic variation, we use our results to explain the generally smaller [Formula: see text] values between pairs of continents relative to global [Formula: see text] values. We discuss implications for the interpretation and use of [Formula: see text]. Copyright © 2017 by the Genetics Society of America.

  10. Constraints on the evolution of function-valued traits: a study of growth in Tribolium castaneum.

    PubMed

    Irwin, K K; Carter, P A

    2013-12-01

    Growth trajectories often impact individual fitness. They are continuous by nature and so are amenable to analysis using a function-valued (FV) trait framework to reveal their underlying genetic architecture. Previous studies have found high levels of standing additive genetic (co)variance for growth trajectories despite the expectation that growth should be responding to frequent strong directional selection. In this study, the FV framework is used to estimate the additive genetic covariance function for growth trajectories in larval Tribolium castaneum to address questions about standing additive genetic (co)variance and possible evolutionary constraints on growth and to predict responses to four plausible selection regimes. Results show that additive genetic (co)variance is high at the early ages, but decreases towards later ages in the larval period. A selection gradient function of the same size and in the same direction of the first eigenfunction of the G-function should give the maximal response. However, evolutionary constraints may be acting to keep this maximal response from being realized, through either conflicting effects on survivability and fecundity of larger body size, few evolutionary directions having sufficient additive variance for a response, genetic trade-offs with other traits or physiological regulatory mechanisms. More light may be shed on these constraints through the development of more sophisticated statistical approaches and implementation of additional empirical studies to explicitly test for specific types of constraints.

  11. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  12. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  13. Regulation of axon guidance and extension by three-dimensional constraints.

    PubMed

    Francisco, Herbert; Yellen, Benjamin B; Halverson, Derek S; Friedman, Gary; Gallo, Gianluca

    2007-08-01

    Axons in vivo are guided by molecular signals acting as attractants and repellents, and possibly by physical constraints encountered in the extracellular environment. We analyzed the ability of primary sensory axons to extend and undergo guidance in three-dimensional (3-D) environments generated using photolithography. Confinement of neurons in fully enclosed square chambers decreased the percentage of neurons establishing axons as a function of chamber width. However, the ability to extend an axon in one or more directions allowed axons to form and extend similarly to those on two-dimensional (2-D) substrata. Live imaging of growth cones interacting with the walls of chambers or corridors revealed that growth cones respond to contact with a 3-D constraint by decreasing surface area, and circumvent constraints by repeated sampling of the constraint until an unobstructed path is encountered. Analysis of the ability of axons to turn around corners in corridors revealed that the angle of the corner and corridor width determined the frequency of turning. Finally, we show that the length of axons can be controlled through the use of 3-D constraints. These data demonstrate that 3-D constraints can be used to guide axons, and control the extent of axon formation and the length of axons.

  14. Design constraints of the LST fine guidance sensor

    NASA Technical Reports Server (NTRS)

    Wissinger, A. B.

    1975-01-01

    The LST Fine Guidance Sensor design is shaped by the rate of occurrence of suitable guide stars, the competition for telescope focal plane space with the Science Instruments, and the sensitivity of candidate image motion sensors. The relationship between these parameters is presented, and sensitivity to faint stars is shown to be of prime importance. An interferometric technique of image motion sensing is shown to have improved sensitivity and, therefore, a reduced focal plane area requirement in comparison with other candidate techniques (image-splitting prism and image dissector tube techniques). Another design requirement is speed in acquiring the guide star in order to maximize the time available for science observations. The design constraints are shown parametrically, and modelling results are presented.

  15. Exploring fragment spaces under multiple physicochemical constraints

    NASA Astrophysics Data System (ADS)

    Pärn, Juri; Degen, Jörg; Rarey, Matthias

    2007-06-01

    We present a new algorithm for the enumeration of chemical fragment spaces under constraints. Fragment spaces consist of a set of molecular fragments and a set of rules that specifies how fragments can be combined. Although fragment spaces typically cover an infinite number of molecules, they can be enumerated in case that a physicochemical profile of the requested compounds is given. By using min-max ranges for a number of corresponding properties, our algorithm is able to enumerate all molecules which obey these properties. To speed up the calculation, the given ranges are used directly during the build-up process to guide the selection of fragments. Furthermore, a topology based fragment filter is used to skip most of the redundant fragment combinations. We applied the algorithm to 40 different target classes. For each of these, we generated tailored fragment spaces from sets of known inhibitors and additionally derived ranges for several physicochemical properties. We characterized the target-specific fragment spaces and were able to enumerate the complete chemical subspaces for most of the targets.

  16. Constraint Theory and Roken Bond Bending Constraints in Oxide Glasses

    NASA Astrophysics Data System (ADS)

    Zhang, Min

    The molecular structure of sodium tellurate glasses was established using ^{125}Te absorption and ^{129}I emission Mossbauer spectroscopies, differential scanning calorimetry (DSC), molar volume measurements and powder x-ray diffraction (XRD). The local atomic arrangement in these glasses is found to be different from that in corresponding crystals. This picture does not follow the usual thinking (Ioffe-Regel rule) about glass structure. The experimental evidence for this conclusion derives not only from Mossbauer spectroscopy but also from time-temperature -transformation curve and powder XRD measurements used to examine the crystallization of the bulk glasses. The TTT -curve exhibits both nucleation and growth branches, while XRD scans reveal growth of metastable phases before forming the stable crystalline phases. These results are in harmony with ^{23}Na solid state NMR results that reveal that sodium local environment in a x = 0.20 glass differs qualitatively from that of the crystalline counterpart. Results from DCS and XRD measurements reveal that at x = 0.18 several observables such as, dT_{g}/dx, activation energy for enthalpy relaxation, molar volume and Lamb-Mossbauer f factor, each display a threshold behavior. We believe that the physical origin of this threshold behavior comes from the rigidity percolation threshold. The constraint theory has recently been extended to include one-fold coordinated species and broken bond bending (beta) constraints. The latter was developed and has been applied successfully to many glass systems including the oxides, as we did for the first time in our Science paper, but also to chalcogenides and chalcohalides, etc.. In the experiments, the observed threshold apparently shifts to the over-constrained regime, i.e. > 2.4 in many glass systems. This shift is largely due to broken beta -constraint at some two-fold coordinated atoms, e.g. Se/S in chain segments and oxygen atoms. An example is g-Ge _{x}Se_{1-x } where one

  17. Genetic Counseling

    MedlinePlus

    ... Genetic Counseling Genomic Testing Pathogen Genomics Epidemiology Resources Genetic Counseling Recommend on Facebook Tweet Share Compartir In ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  18. Mice and Men Environmental Balance, Parts Three and Four of an Integrated Science Sequence, Teacher's Guide, 1970 Edition.

    ERIC Educational Resources Information Center

    Portland Project Committee, OR.

    This teacher's guide contains parts three and four of the four-part first year Portland Project, a three-year secondary integrated science curriculum sequence. Part three of the guide deals with topics such as the cell, reproduction, embryology, genetics, genetic diseases, genetics and change, populations, effects of density on populations,…

  19. Constraint counting for frictional jamming

    NASA Astrophysics Data System (ADS)

    Quint, D. A.; Henkes, S.; Schwarz, J. M.

    2012-02-01

    While the frictionless jamming transition has been intensely studied in recent years, more realistic frictional packings are less well understood. In frictionless sphere packings, the transition is predicted by a simple mean-field constraint counting argument, the isostaticity argument. For frictional packings, a modified constraint counting argument, which includes slipping contacts at the Coulomb threshold, has had limited success in accounting for the transition. We propose that the frictional jamming transition is not mean field and is triggered by the nucleation of unstable regions, which are themselves dynamical objects due to the Coulomb criterion. We create frictional packings using MD simulations and test for the presence and shape of rigid clusters with the pebble game to identify the partition of the packing into stable and unstable regions. To understand the dynamics of these unstable regions we follow perturbations at contacts crucial to the stability of the ``frictional house of cards.''

  20. Functional constraints on phenomenological coefficients

    NASA Astrophysics Data System (ADS)

    Klika, Václav; Pavelka, Michal; Benziger, Jay B.

    2017-02-01

    Thermodynamic fluxes (diffusion fluxes, heat flux, etc.) are often proportional to thermodynamic forces (gradients of chemical potentials, temperature, etc.) via the matrix of phenomenological coefficients. Onsager's relations imply that the matrix is symmetric, which reduces the number of unknown coefficients is reduced. In this article we demonstrate that for a class of nonequilibrium thermodynamic models in addition to Onsager's relations the phenomenological coefficients must share the same functional dependence on the local thermodynamic state variables. Thermodynamic models and experimental data should be validated through consistency with the functional constraint. We present examples of coupled heat and mass transport (thermodiffusion) and coupled charge and mass transport (electro-osmotic drag). Additionally, these newly identified constraints further reduce the number of experiments needed to describe the phenomenological coefficient.

  1. Observational constraints on exponential gravity

    SciTech Connect

    Yang, Louis; Lee, Chung-Chi; Luo, Ling-Wei; Geng, Chao-Qiang

    2010-11-15

    We study the observational constraints on the exponential gravity model of f(R)=-{beta}R{sub s}(1-e{sup -R/R}{sub s}). We use the latest observational data including Supernova Cosmology Project Union2 compilation, Two-Degree Field Galaxy Redshift Survey, Sloan Digital Sky Survey Data Release 7, and Seven-Year Wilkinson Microwave Anisotropy Probe in our analysis. From these observations, we obtain a lower bound on the model parameter {beta} at 1.27 (95% C.L.) but no appreciable upper bound. The constraint on the present matter density parameter is 0.245<{Omega}{sub m}{sup 0}<0.311 (95% C.L.). We also find out the best-fit value of model parameters on several cases.

  2. A compendium of chameleon constraints

    NASA Astrophysics Data System (ADS)

    Burrage, Clare; Sakstein, Jeremy

    2016-11-01

    The chameleon model is a scalar field theory with a screening mechanism that explains how a cosmologically relevant light scalar can avoid the constraints of intra-solar-system searches for fifth-forces. The chameleon is a popular dark energy candidate and also arises in f(R) theories of gravity. Whilst the chameleon is designed to avoid historical searches for fifth-forces it is not unobservable and much effort has gone into identifying the best observables and experiments to detect it. These results are not always presented for the same models or in the same language, a particular problem when comparing astrophysical and laboratory searches making it difficult to understand what regions of parameter space remain. Here we present combined constraints on the chameleon model from astrophysical and laboratory searches for the first time and identify the remaining windows of parameter space. We discuss the implications for cosmological chameleon searches and future small-scale probes.

  3. Integral Constraints and MHD Stability

    NASA Astrophysics Data System (ADS)

    Jensen, T. H.

    2003-10-01

    Determining stability of a plasma in MHD equilibrium, energetically isolated by a conducting wall, requires an assumption on what governs the dynamics of the plasma. One example is the assumption that the plasma obeys ideal MHD, leading to the well known ``δ W" criteria [I. Bernstein, et al., Proc. Roy. Soc. London A244, 17 (1958)]. A radically different approach was used by Taylor [J.B. Taylor, Rev. Mod. Phys. 58, 741 (1986)] in assuming that the dynamics of the plasma is restricted only by the requirement that helicity, an integral constant associated with the plasma, is conserved. The relevancy of Taylor's assumption is supported by the agreement between resulting theoretical results and experimental observations. Another integral constraint involves the canonical angular momentum of the plasma particles. One consequence of using this constraint is that tokamak plasmas have no poloidal current in agreement with some current hole tokamak observations [T.H. Jensen, Phys. Lett. A 305, 183 (2002)].

  4. Constraint checking during error recovery

    NASA Technical Reports Server (NTRS)

    Lutz, Robyn R.; Wong, Johnny S. K.

    1993-01-01

    The system-level software onboard a spacecraft is responsible for recovery from communication, power, thermal, and computer-health anomalies that may occur. The recovery must occur without disrupting any critical scientific or engineering activity that is executing at the time of the error. Thus, the error-recovery software may have to execute concurrently with the ongoing acquisition of scientific data or with spacecraft maneuvers. This work provides a technique by which the rules that constrain the concurrent execution of these processes can be modeled in a graph. An algorithm is described that uses this model to validate that the constraints hold for all concurrent executions of the error-recovery software with the software that controls the science and engineering activities of the spacecraft. The results are applicable to a variety of control systems with critical constraints on the timing and ordering of the events they control.

  5. Genetic Dissection of Neural Circuits

    PubMed Central

    Luo, Liqun; Callaway, Edward M.; Svoboda, Karel

    2009-01-01

    Understanding the principles of information processing in neural circuits requires systematic characterization of the participating cell types and their connections, and the ability to measure and perturb their activity. Genetic approaches promise to bring experimental access to complex neural systems, including genetic stalwarts such as the fly and mouse, but also to nongenetic systems such as primates. Together with anatomical and physiological methods, cell-type-specific expression of protein markers and sensors and transducers will be critical to construct circuit diagrams and to measure the activity of genetically defined neurons. Inactivation and activation of genetically defined cell types will establish causal relationships between activity in specific groups of neurons, circuit function, and animal behavior. Genetic analysis thus promises to reveal the logic of the neural circuits in complex brains that guide behaviors. Here we review progress in the genetic analysis of neural circuits and discuss directions for future research and development. PMID:18341986

  6. Managing Restaurant Tables using Constraints

    NASA Astrophysics Data System (ADS)

    Vidotto, Alfio; Brown, Kenneth N.; Beck, J. Christopher

    Restaurant table management can have significant impact on both profitability and the customer experience. The core of the issue is a complex dynamic combinatorial problem. We show how to model the problem as constraint satisfaction, with extensions which generate flexible seating plans and which maintain stability when changes occur. We describe an implemented system which provides advice to users in real time. The system is currently being evaluated in a restaurant environment.

  7. Macroscopic constraints on string unification

    SciTech Connect

    Taylor, T.R.

    1989-03-01

    The comparison of sting theory with experiment requires a huge extrapolation from the microscopic distances, of order of the Planck length, up to the macroscopic laboratory distances. The quantum effects give rise to large corrections to the macroscopic predictions of sting unification. I discus the model-independent constraints on the gravitational sector of string theory due to the inevitable existence of universal Fradkin-Tseytlin dilatons. 9 refs.

  8. Counting Heron Triangles with Constraints

    DTIC Science & Technology

    2013-01-25

    A3 INTEGERS 13 (2013) COUNTING HERON TRIANGLES WITH CONSTRAINTS Pantelimon Stănică Applied Mathematics, Naval Postgraduate School, Monterey...12, Revised: 10/12/12, Accepted: 1/13/13, Published: 1/25/13 Abstract Heron triangles have the property that all three of their sides as well as their...area are positive integers. In this paper, we give some estimates for the number of Heron triangles with two of their sides fixed. We provide a

  9. Adaptive Search through Constraint Violations

    DTIC Science & Technology

    1990-01-01

    ZIP Code) 3939 O’Hara Street 800 North Quincy Street Pittsburgh, PA 15260 Arlington, VA 22217-5000 8a NAME OF FUNDING/SPONSORING Bb OFFICE SYMBOL 9...Pittsburgh, PA . Smith, D. A., Greeno, J. G., & Vitolo, T. M., (in press). A model of competence for counting. Cognitive Science. VanLehn, K. (in press...1990). Adaptive search through constraint violations (Technical Report No. KUL-90-01). Pittsburgh, PA : Learning Research and Development Center

  10. Virasoro constraint for Nekrasov instanton partition function

    NASA Astrophysics Data System (ADS)

    Kanno, Shoichi; Matsuo, Yutaka; Zhang, Hong

    2012-10-01

    We show that Nekrasov instanton partition function for SU( N ) gauge theories satisfies recursion relations in the form of U(1)+Virasoro constraints when β = 1. The constraints give a direct support for AGT conjecture for general quiver gauge theories.

  11. User's guide for SOL/QPSOL: a Fortran package for quadratic programming

    SciTech Connect

    Gill, P.E.; Murray, W.; Saunders, M.A.; Wright, M.H.

    1983-07-01

    This report forms the user's guide for Version 3.1 of SOL/QPSOL, a set of Fortran subroutines designed to locate the minimum value of an arbitrary quadratic function subject to linear constraints and simple upper and lower bounds. If the quadratic function is convex, a global minimum is found; otherwise, a local minimum is found. The method used is most efficient when many constraints or bounds are active at the solution. QPSOL treats the Hessian and general constraints as dense matrices, and hence is not intended for large sparse problems. This document replaces the previous user's guide of June 1982.

  12. Infrared constraints on ultraviolet theories

    NASA Astrophysics Data System (ADS)

    Tsai, Yuhsin

    2012-01-01

    While our current paradigm of particle physics, the Standard Model (SM), has been extremely successful at explaining experiments, it is theoretically incomplete and must be embedded into a larger framework. In this thesis, we review the main motivations for theories beyond the SM (BSM) and the ways such theories can be constrained using low energy physics. The hierarchy problem, neutrino mass and the existence of dark matter (DM) are the main reasons why the SM is incomplete . Two of the most plausible theories that may solve the hierarchy problem are the Randall-Sundrum (RS) models and supersymmetry (SUSY). RS models usually suffer from strong flavor constraints, while SUSY models produce extra degrees of freedom that need to be hidden from current experiments. To show the importance of infrared (IR) physics constraints, we discuss the flavor bounds on the anarchic RS model in both the lepton and quark sectors. For SUSY models, we discuss the difficulties in obtaining a phenomenologically allowed gaugino mass, its relation to R-symmetry breaking, and how to build a model that avoids this problem. For the neutrino mass problem, we discuss the idea of generating small neutrino masses using compositeness. By requiring successful leptogenesis and the existence of warm dark matter (WDM), we can set various constraints on the hidden composite sector. Finally, to give an example of model independent bounds from collider experiments, we show how to constrain the DM-SM particle interactions using collider results with an effective coupling description.

  13. Constraint programming based biomarker optimization.

    PubMed

    Zhou, Manli; Luo, Youxi; Sun, Guoquan; Mai, Guoqin; Zhou, Fengfeng

    2015-01-01

    Efficient and intuitive characterization of biological big data is becoming a major challenge for modern bio-OMIC based scientists. Interactive visualization and exploration of big data is proven to be one of the successful solutions. Most of the existing feature selection algorithms do not allow the interactive inputs from users in the optimizing process of feature selection. This study investigates this question as fixing a few user-input features in the finally selected feature subset and formulates these user-input features as constraints for a programming model. The proposed algorithm, fsCoP (feature selection based on constrained programming), performs well similar to or much better than the existing feature selection algorithms, even with the constraints from both literature and the existing algorithms. An fsCoP biomarker may be intriguing for further wet lab validation, since it satisfies both the classification optimization function and the biomedical knowledge. fsCoP may also be used for the interactive exploration of bio-OMIC big data by interactively adding user-defined constraints for modeling.

  14. Infrared Constraint on Ultraviolet Theories

    SciTech Connect

    Tsai, Yuhsin

    2012-08-01

    While our current paradigm of particle physics, the Standard Model (SM), has been extremely successful at explaining experiments, it is theoretically incomplete and must be embedded into a larger framework. In this thesis, we review the main motivations for theories beyond the SM (BSM) and the ways such theories can be constrained using low energy physics. The hierarchy problem, neutrino mass and the existence of dark matter (DM) are the main reasons why the SM is incomplete . Two of the most plausible theories that may solve the hierarchy problem are the Randall-Sundrum (RS) models and supersymmetry (SUSY). RS models usually suffer from strong flavor constraints, while SUSY models produce extra degrees of freedom that need to be hidden from current experiments. To show the importance of infrared (IR) physics constraints, we discuss the flavor bounds on the anarchic RS model in both the lepton and quark sectors. For SUSY models, we discuss the difficulties in obtaining a phenomenologically allowed gaugino mass, its relation to R-symmetry breaking, and how to build a model that avoids this problem. For the neutrino mass problem, we discuss the idea of generating small neutrino masses using compositeness. By requiring successful leptogenesis and the existence of warm dark matter (WDM), we can set various constraints on the hidden composite sector. Finally, to give an example of model independent bounds from collider experiments, we show how to constrain the DM–SM particle interactions using collider results with an effective coupling description.

  15. A Hybrid Constraint Representation and Reasoning Framework

    NASA Technical Reports Server (NTRS)

    Golden, Keith; Pang, Wanlin

    2004-01-01

    In this paper, we introduce JNET, a novel constraint representation and reasoning framework that supports procedural constraints and constraint attachments, providing a flexible way of integrating the constraint system with a runtime software environment and improving its applicability. We describe how JNET is applied to a real-world problem - NASA's Earth-science data processing domain, and demonstrate how JNET can be extended, without any knowledge of how it is implemented, to meet the growing demands of real-world applications.

  16. Learning and Parallelization Boost Constraint Search

    ERIC Educational Resources Information Center

    Yun, Xi

    2013-01-01

    Constraint satisfaction problems are a powerful way to abstract and represent academic and real-world problems from both artificial intelligence and operations research. A constraint satisfaction problem is typically addressed by a sequential constraint solver running on a single processor. Rather than construct a new, parallel solver, this work…

  17. Learning and Parallelization Boost Constraint Search

    ERIC Educational Resources Information Center

    Yun, Xi

    2013-01-01

    Constraint satisfaction problems are a powerful way to abstract and represent academic and real-world problems from both artificial intelligence and operations research. A constraint satisfaction problem is typically addressed by a sequential constraint solver running on a single processor. Rather than construct a new, parallel solver, this work…

  18. Thermodynamic optimization under topological constraints

    NASA Astrophysics Data System (ADS)

    Balakumar, Thevika

    Computational thermodynamics is a powerful tool for solving practically important problems including the design of new materials and the analysis of their internal and external stability. This thesis contributes to computational thermodynamics by proposing several practical solutions to eliminate the so-called thermodynamic artifacts rather frequently found in thermodynamic assessments. First, a method is developed to eliminate the artifacts such as inverted miscibility gaps in the liquid phase at high-temperatures and reappearance of the liquid phase at low-temperatures or reappearance of a solid phase at elevated temperatures. This method is based on introducing a sufficiently dense mesh of knots (not related to experimental points utilized in the optimization) and ensuring that specific inequality conditions (topological constraints) governing the appearance of the phase diagram are satisfied in these knots. A feasibility of the approach proposed is exemplified by carrying out a re-optimization of the Mg-Sb system. Generally re-optimization of a system would take months to get the optimized results. Hence, to minimize time needed to get rid of artifacts, two different quick correction methods are developed to eliminate the unrealistic inverted miscibility gap in the liquid phase at elevated temperatures. Both methods employ optimization under topological constraints via controlling the sign of the second derivative of the Gibbs energy. Their applicability is exemplified on the Sn-Zr system. Also, a theoretical study was done on undulate phase boundaries. Usually, an inflection point on a phase boundary is considered as an unambiguous indication that one of the phases participating in the equilibrium is internally unstable, i.e., that it is prone to phase separation. It has been generally assumed that an inflection point may occur only if the thermodynamic model of this phase contains an excess Gibbs energy term. It is shown that in contrast to this assumption

  19. Constraints to commercialization of algal fuels.

    PubMed

    Chisti, Yusuf

    2013-09-10

    Production of algal crude oil has been achieved in various pilot scale facilities, but whether algal fuels can be produced in sufficient quantity to meaningfully displace petroleum fuels, has been largely overlooked. Limitations to commercialization of algal fuels need to be understood and addressed for any future commercialization. This review identifies the major constraints to commercialization of transport fuels from microalgae. Algae derived fuels are expensive compared to petroleum derived fuels, but this could change. Unfortunately, improved economics of production are not sufficient for an environmentally sustainable production, or its large scale feasibility. A low-cost point supply of concentrated carbon dioxide colocated with the other essential resources is necessary for producing algal fuels. An insufficiency of concentrated carbon dioxide is actually a major impediment to any substantial production of algal fuels. Sustainability of production requires the development of an ability to almost fully recycle the phosphorous and nitrogen nutrients that are necessary for algae culture. Development of a nitrogen biofixation ability to support production of algal fuels ought to be an important long term objective. At sufficiently large scale, a limited supply of freshwater will pose a significant limitation to production even if marine algae are used. Processes for recovering energy from the algal biomass left after the extraction of oil, are required for achieving a net positive energy balance in the algal fuel oil. The near term outlook for widespread use of algal fuels appears bleak, but fuels for niche applications such as in aviation may be likely in the medium term. Genetic and metabolic engineering of microalgae to boost production of fuel oil and ease its recovery, are essential for commercialization of algal fuels. Algae will need to be genetically modified for improved photosynthetic efficiency in the long term. Copyright © 2013 Elsevier B.V. All

  20. The probability of parallel genetic evolution from standing genetic variation.

    PubMed

    MacPherson, A; Nuismer, S L

    2017-02-01

    Parallel evolution is often assumed to result from repeated adaptation to novel, yet ecologically similar, environments. Here, we develop and analyse a mathematical model that predicts the probability of parallel genetic evolution from standing genetic variation as a function of the strength of phenotypic selection and constraints imposed by genetic architecture. Our results show that the probability of parallel genetic evolution increases with the strength of natural selection and effective population size and is particularly likely to occur for genes with large phenotypic effects. Building on these results, we develop a Bayesian framework for estimating the strength of parallel phenotypic selection from genetic data. Using extensive individual-based simulations, we show that our estimator is robust across a wide range of genetic and evolutionary scenarios and provides a useful tool for rigorously testing the hypothesis that parallel genetic evolution is the result of adaptive evolution. An important result that emerges from our analyses is that existing studies of parallel genetic evolution frequently rely on data that is insufficient for distinguishing between adaptive evolution and neutral evolution driven by random genetic drift. Overcoming this challenge will require sampling more populations and the inclusion of larger numbers of loci.

  1. Theory of constraints for publicly funded health systems.

    PubMed

    Sadat, Somayeh; Carter, Michael W; Golden, Brian

    2013-03-01

    Originally developed in the context of publicly traded for-profit companies, theory of constraints (TOC) improves system performance through leveraging the constraint(s). While the theory seems to be a natural fit for resource-constrained publicly funded health systems, there is a lack of literature addressing the modifications required to adopt TOC and define the goal and performance measures. This paper develops a system dynamics representation of the classical TOC's system-wide goal and performance measures for publicly traded for-profit companies, which forms the basis for developing a similar model for publicly funded health systems. The model is then expanded to include some of the factors that affect system performance, providing a framework to apply TOC's process of ongoing improvement in publicly funded health systems. Future research is required to more accurately define the factors affecting system performance and populate the model with evidence-based estimates for various parameters in order to use the model to guide TOC's process of ongoing improvement.

  2. Optical mechanical analogy and nonlinear nonholonomic constraints.

    PubMed

    Bloch, Anthony M; Rojo, Alberto G

    2016-02-01

    In this paper we establish a connection between particle trajectories subject to a nonholonomic constraint and light ray trajectories in a variable index of refraction. In particular, we extend the analysis of systems with linear nonholonomic constraints to the dynamics of particles in a potential subject to nonlinear velocity constraints. We contrast the long time behavior of particles subject to a constant kinetic energy constraint (a thermostat) to particles with the constraint of parallel velocities. We show that, while in the former case the velocities of each particle equalize in the limit, in the latter case all the kinetic energies of each particle remain the same.

  3. Resolving manipulator redundancy under inequality constraints

    SciTech Connect

    Cheng, F.T.; Chen, T.H.; Sun, Y.Y. . Dept. of Electrical Engineering)

    1994-02-01

    Due to hardware limitations, physical constraints such as joint rate bounds, joint angle limits, and joint torque constraints always exist. In this paper, these constraints are considered into the general formulation of the redundant inverse kinematic problem. To take these physical constraints into account, the computationally efficient Compact Quadratic Programming (QP) method is formed to resolve the constrained kinematic redundancy problem. In addition, the Compact-Inverse QP method is also formulated to remedy the unescapable singularity problem with inequality constraints. Two examples are given to demonstrate the generality and superiority of these two methods: to eliminate the drift phenomenon caused by self motion and to remedy saturation-type nonlinearity problem.

  4. Traj_opt User's Guide

    NASA Technical Reports Server (NTRS)

    Saunders, David A.

    2005-01-01

    Trajectory optimization program Traj_opt was developed at Ames Research Center to help assess the potential benefits of ultrahigh temperature ceramic materials applied to reusable space vehicles with sharp noses and wing leading edges. Traj_opt loosely couples the Ames three-degrees-of-freedom trajectory package Traj (see NASA-TM-2004-212847) with the SNOPT optimization package (Stanford University Technical Report SOL 98-1). Traj_opt version January 22, 2003 is covered by this user guide. The program has been applied extensively to entry and ascent abort trajectory calculations for sharp and blunt crew transfer vehicles. The main optimization variables are control points for the angle of attack and bank angle time histories. No propulsion options are provided, but numerous objective functions may be specified and the nonlinear constraints implemented include a distributed surface heating constraint capability. Aero-capture calculations are also treated with an option to minimize orbital eccentricity at apoapsis. Traj_opt runs efficiently on a single processor, using forward or central differences for the gradient calculations. Results may be displayed conveniently with Gnuplot scripts. Control files recommended for five standard reentry and ascent abort trajectories are included along with detailed descriptions of the inputs and outputs.

  5. Constraints on the timeon model

    NASA Astrophysics Data System (ADS)

    Araki, Takeshi; Geng, C. Q.

    2009-04-01

    The timeon model recently proposed by Friedberg and Lee has a potential problem of flavor changing neutral currents (FCNCs) if the mass of the timeon is small. In order to avoid, we introduce a small dimensionless parameter to suppress FCNCs. Even in this case, we find that the timeon mass must be larger than 151 GeV to satisfy all the constraints from processes involving FCNCs in the quark sectors. We also extend the timeon model to the lepton sector and examine the leptonic processes.

  6. Trajectory constraints in qualitative simulation

    SciTech Connect

    Brajnik, G.; Clancy, D.J.

    1996-12-31

    We present a method for specifying temporal constraints on trajectories of dynamical systems and enforcing them during qualitative simulation. This capability can be used to focus a simulation, simulate non-autonomous and piecewise-continuous systems, reason about boundary condition problems and incorporate observations into the simulation. The method has been implemented in TeQSIM, a qualitative simulator that combines the expressive power of qualitative differential equations with temporal logic. It interleaves temporal logic model checking with the simulation to constrain and refine the resulting predicted behaviors and to inject discontinuous changes into the simulation.

  7. Killing symmetries as Hamiltonian constraints

    NASA Astrophysics Data System (ADS)

    Lusanna, Luca

    2016-02-01

    The existence of a Killing symmetry in a gauge theory is equivalent to the addition of extra Hamiltonian constraints in its phase space formulation, which imply restrictions both on the Dirac observables (the gauge invariant physical degrees of freedom) and on the gauge freedom. When there is a time-like Killing vector field only pure gauge electromagnetic fields survive in Maxwell theory in Minkowski space-time, while in ADM canonical gravity in asymptotically Minkowskian space-times only inertial effects without gravitational waves survive.

  8. QPO Constraints on Neutron Stars

    NASA Technical Reports Server (NTRS)

    Miller, M. Coleman

    2005-01-01

    The kilohertz frequencies of QPOs from accreting neutron star systems imply that they are generated in regions of strong gravity, close to the star. This suggests that observations of the QPOs can be used to constrain the properties of neutron stars themselves, and in particular to inform us about the properties of cold matter beyond nuclear densities. Here we discuss some relatively model-insensitive constraints that emerge from the kilohertz QPOs, as well as recent developments that may hint at phenomena related to unstable circular orbits outside neutron stars.

  9. Closure constraints for hyperbolic tetrahedra

    NASA Astrophysics Data System (ADS)

    Charles, Christoph; Livine, Etera R.

    2015-07-01

    We investigate the generalization of loop gravity's twisted geometries to a q-deformed gauge group. In the standard undeformed case, loop gravity is a formulation of general relativity as a diffeomorphism-invariant SU(2) gauge theory. Its classical states are graphs provided with algebraic data. In particular, closure constraints at every node of the graph ensure their interpretation as twisted geometries. Dual to each node, one has a polyhedron embedded in flat space {{{R}}3}. One then glues them, allowing for both curvature and torsion. It was recently conjectured that q-deforming the gauge group SU(2) would allow us to account for a non-vanishing cosmological constant Λ \

  10. A Guide to Health Occupations. Teacher's Guide.

    ERIC Educational Resources Information Center

    Cheu, Janey M. Y.; And Others

    This guide is intended to assist teachers in using a companion health career reference as a class text for introducing students to the health field. The first two sections describe the purposes and organization of the companion guide. Discussed next are ways of helping students explore health career opportunities and options and come to understand…

  11. Design Constraints on a Synthetic Metabolism

    PubMed Central

    Bilgin, Tugce; Wagner, Andreas

    2012-01-01

    A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable simultaneously. We here use a recently developed technique to create random metabolic networks with pre-specified properties to quantify trade-offs between these and other properties. We find that for every additional molecule to be synthesized a network needs on average three additional reactions. For every additional carbon source to be utilized, it needs on average two additional reactions. Networks able to synthesize 20 biomass molecules from each of 20 alternative sole carbon sources need to have at least 260 reactions. This number increases to 518 reactions for networks that can synthesize more than 60 molecules from each of 80 carbon sources. The maximally achievable rate of biosynthesis decreases by approximately 5 percent for every additional molecule to be synthesized. Biochemically related molecules can be synthesized at higher rates, because their synthesis produces less waste. Overall, the variables we study can explain 87 percent of variation in network size and 84 percent of the variation in synthesis rate. The constraints we identify prescribe broad boundary conditions that can help to guide synthetic metabolism design. PMID:22768162

  12. COLLABORATIVE GUIDE: A REEF MANAGER'S GUIDE TO ...

    EPA Pesticide Factsheets

    Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Referred to as A Reef Manager's Guide to Coral Bleaching, the guide will provide coral reef managers with the latest scientific information on the causes of coral bleaching and new management strategies for responding to this significant threat to coral reef ecosystems. Innovative strategies to conserve the world's coral reefs are included in a new guide released today by NOAA, and the Australian Great Barrier Reef Marine Park Authority, with author contributions from a variety of international partners from government agencies, non-governmental organizations, and academic institutions. Dr. Jordan West, of the National Center for Environmental Assessment, was a major contributor to the guide. Referred to as

  13. Cognitive constraints on motor imagery.

    PubMed

    Dahm, Stephan F; Rieger, Martina

    2016-03-01

    Executed bimanual movements are prepared slower when moving to symbolically different than when moving to symbolically same targets and when targets are mapped to target locations in a left/right fashion than when they are mapped in an inner/outer fashion [Weigelt et al. (Psychol Res 71:238-447, 2007)]. We investigated whether these cognitive bimanual coordination constraints are observable in motor imagery. Participants performed fast bimanual reaching movements from start to target buttons. Symbolic target similarity and mapping were manipulated. Participants performed four action conditions: one execution and three imagination conditions. In the latter they indicated starting, ending, or starting and ending of the movement. We measured movement preparation (RT), movement execution (MT) and the combined duration of movement preparation and execution (RTMT). In all action conditions RTs and MTs were longer in movements towards different targets than in movements towards same targets. Further, RTMTs were longer when targets were mapped to target locations in a left/right fashion than when they were mapped in an inner/outer fashion, again in all action conditions. RTMTs in imagination and execution were similar, apart from the imagination condition in which participants indicated the start and the end of the movement. Here MTs, but not RTs, were longer than in the execution condition. In conclusion, cognitive coordination constraints are present in the motor imagery of fast (<1600 ms) bimanual movements. Further, alternations between inhibition and execution may prolong the duration of motor imagery.

  14. Shaping tissues by balancing active forces and geometric constraints

    NASA Astrophysics Data System (ADS)

    Foolen, Jasper; Yamashita, Tadahiro; Kollmannsberger, Philip

    2016-02-01

    The self-organization of cells into complex tissues during growth and regeneration is a combination of physical-mechanical events and biochemical signal processing. Cells actively generate forces at all stages in this process, and according to the laws of mechanics, these forces result in stress fields defined by the geometric boundary conditions of the cell and tissue. The unique ability of cells to translate such force patterns into biochemical information and vice versa sets biological tissues apart from any other material. In this topical review, we summarize the current knowledge and open questions of how forces and geometry act together on scales from the single cell to tissues and organisms, and how their interaction determines biological shape and structure. Starting with a planar surface as the simplest type of geometric constraint, we review literature on how forces during cell spreading and adhesion together with geometric constraints impact cell shape, stress patterns, and the resulting biological response. We then move on to include cell-cell interactions and the role of forces in monolayers and in collective cell migration, and introduce curvature at the transition from flat cell sheets to three-dimensional (3D) tissues. Fibrous 3D environments, as cells experience them in the body, introduce new mechanical boundary conditions and change cell behaviour compared to flat surfaces. Starting from early work on force transmission and collagen remodelling, we discuss recent discoveries on the interaction with geometric constraints and the resulting structure formation and network organization in 3D. Recent literature on two physiological scenarios—embryonic development and bone—is reviewed to demonstrate the role of the force-geometry balance in living organisms. Furthermore, the role of mechanics in pathological scenarios such as cancer is discussed. We conclude by highlighting common physical principles guiding cell mechanics, tissue patterning and

  15. AQUATOX Setup Guide

    EPA Pesticide Factsheets

    The new Guidance in AQUATOX Setup and Application provides a quick start guide to introduce major model features, as well as being a type of cookbook to guide basic model setup, calibration, and validation.

  16. Cirrhosis: A Patient's Guide

    MedlinePlus

    ... ZIP code here Cirrhosis: A Patient's Guide for Health Care Providers Cirrhosis: A Patient's Guide March 2007 Contents ... how best to treat it. What will your health care provider do about cirrhosis? People with cirrhosis need ...

  17. Reformulating Constraints for Compilability and Efficiency

    NASA Technical Reports Server (NTRS)

    Tong, Chris; Braudaway, Wesley; Mohan, Sunil; Voigt, Kerstin

    1992-01-01

    KBSDE is a knowledge compiler that uses a classification-based approach to map solution constraints in a task specification onto particular search algorithm components that will be responsible for satisfying those constraints (e.g., local constraints are incorporated in generators; global constraints are incorporated in either testers or hillclimbing patchers). Associated with each type of search algorithm component is a subcompiler that specializes in mapping constraints into components of that type. Each of these subcompilers in turn uses a classification-based approach, matching a constraint passed to it against one of several schemas, and applying a compilation technique associated with that schema. While much progress has occurred in our research since we first laid out our classification-based approach [Ton91], we focus in this paper on our reformulation research. Two important reformulation issues that arise out of the choice of a schema-based approach are: (1) compilability-- Can a constraint that does not directly match any of a particular subcompiler's schemas be reformulated into one that does? and (2) Efficiency-- If the efficiency of the compiled search algorithm depends on the compiler's performance, and the compiler's performance depends on the form in which the constraint was expressed, can we find forms for constraints which compile better, or reformulate constraints whose forms can be recognized as ones that compile poorly? In this paper, we describe a set of techniques we are developing for partially addressing these issues.

  18. Guide tube flow diffuser

    SciTech Connect

    Berringer, R.T.; Myron, D.L.

    1980-11-04

    A nuclear reactor upper internal guide tube has a flow diffuser integral with its bottom end. The guide tube provides guidance for control rods during their ascent or descent from the reactor core. The flow diffuser serves to divert the upward flow of reactor coolant around the outside of the guide tube thereby limiting the amount of coolant flow and turbulence within the guide tube, thus enhancing the ease of movement of the control rods.

  19. Chaplain Personnel Information Guide

    DTIC Science & Technology

    1991-04-15

    documnt may not be Mased for opem pisbiktao. si it hu been deajed by the appropiate miitay svice ot oervmnent qaeny. CHAPLAIN PERSONNEL INFORMATION GUIDE ...Include Security Classification) Chaplain Personnel Information Guide 12 PERSONAL AUTHOR(S) Chaplain (LTC) Jerry W. Black 13a. TYPE OF REPORT 13b...personnel information guide called the "Red Book." This guide contains information papers that are updated annually on subjects frequently discussed among the

  20. Electricity Occupations Curriculum Guide.

    ERIC Educational Resources Information Center

    Technical Education Research Center, Champaign, IL.

    The first of four main sections of the electrical occupations curriculum guide is an introduction which describes the design and use of the guide and which provides five pages of suggested curriculum resources. Section two contains job descriptions for 18 electrical occupations. For each occupation the guide explains industry's expectations of the…

  1. Managerial Accounting. Study Guide.

    ERIC Educational Resources Information Center

    Plachta, Leonard E.

    This self-instructional study guide is part of the materials for a college-level programmed course in managerial accounting. The study guide is intended for use by students in conjuction with a separate textbook, Horngren's "Accounting for Management Control: An Introduction," and a workbook, Curry's "Student Guide to Accounting for Management…

  2. Program Resource Guide.

    ERIC Educational Resources Information Center

    National School Resource Network, Washington, DC.

    This program resource guide is a compilation of all programs and projects on preventing school violence and vandalism referenced in National School Resource Network (NSRN) materials. The programs cited are described in NSRN trainers' guides, participant guides, technical assistance bulletins, an "Aha" listing, and a compendium. The index is…

  3. Radon Guide for Tenants

    EPA Pesticide Factsheets

    This guide is for people who rent their apartments or houses. The guide explains what radon is, and how to find out if there is a radon problem in your home. The guide also talks about what you can do if there are high radon levels in your home.

  4. Populations, Teacher's Guide.

    ERIC Educational Resources Information Center

    Conard, David; Lawson, Chester A.

    This Teacher's Guide is designed for use with the Science Curriculum Improvement Study's (SCIS) unit Population. Populations is the third of a six-unit sequence of SCIS's Life Science Program for grades K-6. The Populations guide consists of activity outlines along with suggestions for guiding children's observation and manipulations of living…

  5. Genetic Disorders

    MedlinePlus

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  6. Genetic counseling

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

  7. Genetic Manipulation

    ERIC Educational Resources Information Center

    Klein, David

    1973-01-01

    Knowledge of genetic manipulations opens the door to ambitious possibilities of inhabiting the world with genetically perfect human beings. Legal, technological and social problems are involved. Attempts must be made to identify hereditary complaints in individuals. (PS)

  8. Genetic Mapping

    MedlinePlus

    ... Genetic Education Resources for Teachers Genomic Careers National DNA Day Online Education Kit Online Genetics Education Resources ... prevalent. Using various laboratory techniques, the scientists isolate DNA from these samples and examine it for unique ...

  9. New Genetics

    MedlinePlus

    ... Organisms RNA Interference The New Genetics is a science education booklet explains the role of genes in health and disease, the basics of DNA and its molecular cousin RNA, and new directions in genetic research. ...

  10. Guidelines on the use of molecular genetics in reintroduction programs

    Treesearch

    Michael K. Schwartz

    2005-01-01

    The use of molecular genetics can play a key role in reintroduction efforts. Prior to the introduction of any individuals, molecular genetics can be used to identify the most appropriate source population for the reintroduction, ensure that no relic populations exist in the reintroduction area, and guide captive breeding programs. The use of molecular genetics post-...

  11. Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes.

    PubMed

    Adnane, Bargaz; Mainassara, Zaman-Allah; Mohamed, Farissi; Mohamed, Lazali; Jean-Jacques, Drevon; Rim, Maougal T; Georg, Carlsson

    2015-08-13

    Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled-traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints.

  12. Physiological and Molecular Aspects of Tolerance to Environmental Constraints in Grain and Forage Legumes

    PubMed Central

    Bargaz, Adnane; Zaman-Allah, Mainassara; Farissi, Mohamed; Lazali, Mohamed; Drevon, Jean-Jacques; Maougal, Rim T.; Carlsson, Georg

    2015-01-01

    Despite the agronomical and environmental advantages of the cultivation of legumes, their production is limited by various environmental constraints such as water or nutrient limitation, frost or heat stress and soil salinity, which may be the result of pedoclimatic conditions, intensive use of agricultural lands, decline in soil fertility and environmental degradation. The development of more sustainable agroecosystems that are resilient to environmental constraints will therefore require better understanding of the key mechanisms underlying plant tolerance to abiotic constraints. This review provides highlights of legume tolerance to abiotic constraints with a focus on soil nutrient deficiencies, drought, and salinity. More specifically, recent advances in the physiological and molecular levels of the adaptation of grain and forage legumes to abiotic constraints are discussed. Such adaptation involves complex multigene controlled-traits which also involve multiple sub-traits that are likely regulated under the control of a number of candidate genes. This multi-genetic control of tolerance traits might also be multifunctional, with extended action in response to a number of abiotic constraints. Thus, concrete efforts are required to breed for multifunctional candidate genes in order to boost plant stability under various abiotic constraints. PMID:26287163

  13. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  14. Genetic modification and genetic determinism.

    PubMed

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  15. Automatic generation of computable implementation guides from clinical information models.

    PubMed

    Boscá, Diego; Maldonado, José Alberto; Moner, David; Robles, Montserrat

    2015-06-01

    Clinical information models are increasingly used to describe the contents of Electronic Health Records. Implementation guides are a common specification mechanism used to define such models. They contain, among other reference materials, all the constraints and rules that clinical information must obey. However, these implementation guides typically are oriented to human-readability, and thus cannot be processed by computers. As a consequence, they must be reinterpreted and transformed manually into an executable language such as Schematron or Object Constraint Language (OCL). This task can be difficult and error prone due to the big gap between both representations. The challenge is to develop a methodology for the specification of implementation guides in such a way that humans can read and understand easily and at the same time can be processed by computers. In this paper, we propose and describe a novel methodology that uses archetypes as basis for generation of implementation guides. We use archetypes to generate formal rules expressed in Natural Rule Language (NRL) and other reference materials usually included in implementation guides such as sample XML instances. We also generate Schematron rules from NRL rules to be used for the validation of data instances. We have implemented these methods in LinkEHR, an archetype editing platform, and exemplify our approach by generating NRL rules and implementation guides from EN ISO 13606, openEHR, and HL7 CDA archetypes.

  16. Causality constraints in conformal field theory

    SciTech Connect

    Hartman, Thomas; Jain, Sachin; Kundu, Sandipan

    2016-05-17

    Causality places nontrivial constraints on QFT in Lorentzian signature, for example fixing the signs of certain terms in the low energy Lagrangian. In d dimensional conformal field theory, we show how such constraints are encoded in crossing symmetry of Euclidean correlators, and derive analogous constraints directly from the conformal bootstrap (analytically). The bootstrap setup is a Lorentzian four-point function corresponding to propagation through a shockwave. Crossing symmetry fixes the signs of certain log terms that appear in the conformal block expansion, which constrains the interactions of low-lying operators. As an application, we use the bootstrap to rederive the well known sign constraint on the (Φ)4 coupling in effective field theory, from a dual CFT. We also find constraints on theories with higher spin conserved currents. As a result, our analysis is restricted to scalar correlators, but we argue that similar methods should also impose nontrivial constraints on the interactions of spinning operators

  17. Causality constraints in conformal field theory

    NASA Astrophysics Data System (ADS)

    Hartman, Thomas; Jain, Sachin; Kundu, Sandipan

    2016-05-01

    Causality places nontrivial constraints on QFT in Lorentzian signature, for example fixing the signs of certain terms in the low energy Lagrangian. In d dimensional conformal field theory, we show how such constraints are encoded in crossing symmetry of Euclidean correlators, and derive analogous constraints directly from the conformal bootstrap (analytically). The bootstrap setup is a Lorentzian four-point function corresponding to propagation through a shockwave. Crossing symmetry fixes the signs of certain log terms that appear in the conformal block expansion, which constrains the interactions of low-lying operators. As an application, we use the bootstrap to rederive the well known sign constraint on the (∂ ϕ)4 coupling in effective field theory, from a dual CFT. We also find constraints on theories with higher spin conserved currents. Our analysis is restricted to scalar correlators, but we argue that similar methods should also impose nontrivial constraints on the interactions of spinning operators.

  18. Constraint-based interactive assembly planning

    SciTech Connect

    Jones, R.E.; Wilson, R.H.; Calton, T.L.

    1997-03-01

    The constraints on assembly plans vary depending on the product, assembly facility, assembly volume, and many other factors. This paper describes the principles and implementation of a framework that supports a wide variety of user-specified constraints for interactive assembly planning. Constraints from many sources can be expressed on a sequencing level, specifying orders and conditions on part mating operations in a number of ways. All constraints are implemented as filters that either accept or reject assembly operations proposed by the planner. For efficiency, some constraints are supplemented with special-purpose modifications to the planner`s algorithms. Replanning is fast enough to enable a natural plan-view-constrain-replan cycle that aids in constraint discovery and documentation. We describe an implementation of the framework in a computer-aided assembly planning system and experiments applying the system to several complex assemblies. 12 refs., 2 figs., 3 tabs.

  19. Clinical applications of preimplantation genetic testing.

    PubMed

    Brezina, Paul R; Kutteh, William H

    2015-02-19

    Genetic diagnostic technologies are rapidly changing the way medicine is practiced. Preimplantation genetic testing is a well established application of genetic testing within the context of in vitro fertilization cycles. It involves obtaining a cell(s) from a developing embryo in culture, which is then subjected to genetic diagnostic analysis; the resulting information is used to guide which embryos are transferred into the uterus. The potential applications and use of this technology have increased in recent years. Experts agree that preimplantation genetic diagnosis is clinically appropriate for many known genetic disorders. However, some applications of such testing, such as preimplantation genetic screening for aneuploidy, remain controversial. Clinical data suggest that preimplantation genetic screening may be useful, but further studies are needed to quantify the size of the effect and who would benefit most. © BMJ Publishing Group Ltd 2015.

  20. Imaging Genetics

    ERIC Educational Resources Information Center

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  1. Imaging Genetics

    ERIC Educational Resources Information Center

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  2. The genetics of dilated cardiomyopathy

    PubMed Central

    Dellefave, Lisa; McNally, Elizabeth M.

    2010-01-01

    Purpose of review More than forty different individual genes have been implicated in the inheritance of dilated cardiomyopathy. For a subset of these genes, mutations can lead to a spectrum of cardiomyopathy that extends to hypertrophic cardiomyopathy and left ventricular noncompaction. In nearly all cases, there is an increased risk of arrhythmias. With some genetic mutations, extracardiac manifestations are likely to be present. The precise genetic etiology can usually not be discerned from the cardiac and/or extracardiac manifestations and requires molecular genetic diagnosis for prognostic determination and cardiac care. Recent findings Newer technologies are influencing genetic testing, especially cardiomyopathy genetic testing, where an increased number of genes are now routinely being tested simultaneously. While this approach to testing multiple genes is increasing the diagnostic yield, the analysis of multiple genes in one test is also resulting in a large amount of genetic information of unclear significance. Summary Genetic testing is highly useful in the care of patients and families, since it guides diagnosis, influences care and aids in prognosis. However, the large amount of benign human genetic variation may complicate genetic results, and often requires a skilled team to accurately interpret the findings. PMID:20186049

  3. Evaluating the role of reproductive constraints in ant social evolution

    PubMed Central

    Khila, Abderrahman; Abouheif, Ehab

    2010-01-01

    The reproductive division of labour is a key feature of eusociality in ants, where queen and worker castes show dramatic differences in the development of their reproductive organs. To understand the developmental and genetic basis underlying this division of labour, we performed a molecular analysis of ovary function and germ cell development in queens and workers. We show that the processes of ovarian development in queens have been highly conserved relative to the fruitfly Drosophila melanogaster. We also identify specific steps during oogenesis and embryogenesis in which ovarian and germ cell development have been evolutionarily modified in the workers. These modifications, which we call ‘reproductive constraints’, are often assumed to represent neutral degenerations that are a consequence of social evolutionary forces. Based on our developmental and functional analysis of these constraints, however, we propose and discuss the alternative hypothesis that reproductive constraints represent adaptive proximate mechanisms or traits for maintaining social harmony in ants. We apply a multi-level selection framework to help understand the role of these constraints in ant social evolution. A complete understanding of how cooperation, conflict and developmental systems evolve in social groups requires a ‘socio-evo-devo’ approach that integrates social evolutionary and developmental biology. PMID:20083637

  4. Constraints and flexibility in mammalian social behaviour: introduction and synthesis

    PubMed Central

    Kappeler, Peter M.; Barrett, Louise; Blumstein, Daniel T.; Clutton-Brock, Tim H.

    2013-01-01

    This paper introduces a Theme Issue presenting the latest developments in research on the interplay between flexibility and constraint in social behaviour, using comparative datasets, long-term field studies and experimental data from both field and laboratory studies of mammals. We first explain our focus on mammals and outline the main components of their social systems, focusing on variation within- and among-species in numerous aspects of social organization, mating system and social structure. We then review the current state of primarily ultimate explanations of this diversity in social behaviour. We approach the question of how and why the balance between behavioural flexibility and continuity is achieved by discussing the genetic, developmental, ecological and social constraints on hypothetically unlimited behavioural flexibility. We introduce the other contributions to this Theme Issue against this background and conclude that constraints are often crucial to the evolution and expression of behavioural flexibility. In exploring these issues, the enduring relevance of Tinbergen's seminal paper ‘On aims and methods in ethology’, with its advocacy of an integrative, four-pronged approach to studying behaviour becomes apparent: an exceptionally fitting tribute on the 50th anniversary of its publication. PMID:23569286

  5. Thermodynamic constraints on fluctuation phenomena.

    PubMed

    Maroney, O J E

    2009-12-01

    The relationships among reversible Carnot cycles, the absence of perpetual motion machines, and the existence of a nondecreasing globally unique entropy function form the starting point of many textbook presentations of the foundations of thermodynamics. However, the thermal fluctuation phenomena associated with statistical mechanics has been argued to restrict the domain of validity of this basis of the second law of thermodynamics. Here we demonstrate that fluctuation phenomena can be incorporated into the traditional presentation, extending rather than restricting the domain of validity of the phenomenologically motivated second law. Consistency conditions lead to constraints upon the possible spectrum of thermal fluctuations. In a special case this uniquely selects the Gibbs canonical distribution and more generally incorporates the Tsallis distributions. No particular model of microscopic dynamics need be assumed.

  6. Observational constraints on silent quartessence

    NASA Astrophysics Data System (ADS)

    Amendola, L.; Waga, I.; Finelli, F.

    2005-11-01

    We derive new constraints set by SNIa experiments ('gold' data sample of Riess et al), x-ray galaxy cluster data (Allen et al Chandra measurements of the x-ray gas mass fraction in 26 clusters), large scale structure (Sloan Digital Sky Survey spectrum) and cosmic microwave background (WMAP) on the quartessence Chaplygin model. We consider both adiabatic perturbations and intrinsic non-adiabatic perturbations such that the effective sound speed vanishes (silent Chaplygin). We show that for the adiabatic case only models with equation of state parameter |\\alpha |\\lesssim 10^{-2} are allowed: this means that the allowed models are very close to ΛCDM. In the silent case, however, the results are consistent with observations in a much broader range, -0.3<α<0.7.

  7. Constraint Ornstein-Uhlenbeck bridges

    NASA Astrophysics Data System (ADS)

    Mazzolo, Alain

    2017-09-01

    In this paper, we study the Ornstein-Uhlenbeck bridge process (i.e., the Ornstein-Uhlenbeck process conditioned to start and end at fixed points) constraints to have a fixed area under its path. We present both anticipative (in this case, we need the knowledge of the future of the path) and non-anticipative versions of the stochastic process. We obtain the anticipative description thanks to the theory of generalized Gaussian bridges while the non-anticipative representation comes from the theory of stochastic control. For this last representation, a stochastic differential equation is derived which leads to an effective Langevin equation. Finally, we extend our theoretical findings to linear bridge processes.

  8. Physical constraints for pathogen movement.

    PubMed

    Schwarz, Ulrich S

    2015-10-01

    In this pedagogical review, we discuss the physical constraints that pathogens experience when they move in their host environment. Due to their small size, pathogens are living in a low Reynolds number world dominated by viscosity. For swimming pathogens, the so-called scallop theorem determines which kinds of shape changes can lead to productive motility. For crawling or gliding cells, the main resistance to movement comes from protein friction at the cell-environment interface. Viruses and pathogenic bacteria can also exploit intracellular host processes such as actin polymerization and motor-based transport, if they present the appropriate factors on their surfaces. Similar to cancer cells that also tend to cross various barriers, pathogens often combine several of these strategies in order to increase their motility and therefore their chances to replicate and spread. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Atom mapping with constraint programming.

    PubMed

    Mann, Martin; Nahar, Feras; Schnorr, Norah; Backofen, Rolf; Stadler, Peter F; Flamm, Christoph

    2014-01-01

    Chemical reactions are rearrangements of chemical bonds. Each atom in an educt molecule thus appears again in a specific position of one of the reaction products. This bijection between educt and product atoms is not reported by chemical reaction databases, however, so that the "Atom Mapping Problem" of finding this bijection is left as an important computational task for many practical applications in computational chemistry and systems biology. Elementary chemical reactions feature a cyclic imaginary transition state (ITS) that imposes additional restrictions on the bijection between educt and product atoms that are not taken into account by previous approaches. We demonstrate that Constraint Programming is well-suited to solving the Atom Mapping Problem in this setting. The performance of our approach is evaluated for a manually curated subset of chemical reactions from the KEGG database featuring various ITS cycle layouts and reaction mechanisms.

  10. Observational constraints on Galileon cosmology

    NASA Astrophysics Data System (ADS)

    Nesseris, Savvas; de Felice, Antonio; Tsujikawa, Shinji

    2010-12-01

    We study the cosmology of a covariant Galileon field ϕ with five covariant Lagrangians and confront this theory with the most recent cosmological probes: the type Ia supernovae data (Constitution and Union2 sets), cosmic microwave background (WMAP7), and the baryon acoustic oscillations (SDSS7). In the Galileon cosmology with a late-time de Sitter attractor, there is a tracker that attracts solutions with different initial conditions to a common trajectory. Including the cosmic curvature K, we place observational constraints on two distinct cases: (i) the tracker, and (ii) the generic solutions to the equations of motion. We find that the tracker solution can be consistent with the individual observational data, but it is disfavored by the combined data analysis. The generic solutions fare quite well when a nonzero curvature parameter ΩK(0) is taken into account, but the Akaike and Bayesian information criteria show that they are not particularly favored over the ΛCDM model.

  11. Thermodynamic constraints on fluctuation phenomena

    NASA Astrophysics Data System (ADS)

    Maroney, O. J. E.

    2009-12-01

    The relationships among reversible Carnot cycles, the absence of perpetual motion machines, and the existence of a nondecreasing globally unique entropy function form the starting point of many textbook presentations of the foundations of thermodynamics. However, the thermal fluctuation phenomena associated with statistical mechanics has been argued to restrict the domain of validity of this basis of the second law of thermodynamics. Here we demonstrate that fluctuation phenomena can be incorporated into the traditional presentation, extending rather than restricting the domain of validity of the phenomenologically motivated second law. Consistency conditions lead to constraints upon the possible spectrum of thermal fluctuations. In a special case this uniquely selects the Gibbs canonical distribution and more generally incorporates the Tsallis distributions. No particular model of microscopic dynamics need be assumed.

  12. Assessing Multivariate Constraints to Evolution across Ten Long-Term Avian Studies

    PubMed Central

    Teplitsky, Celine; Tarka, Maja; Møller, Anders P.; Nakagawa, Shinichi; Balbontín, Javier; Burke, Terry A.; Doutrelant, Claire; Gregoire, Arnaud; Hansson, Bengt; Hasselquist, Dennis; Gustafsson, Lars; de Lope, Florentino; Marzal, Alfonso; Mills, James A.; Wheelwright, Nathaniel T.; Yarrall, John W.; Charmantier, Anne

    2014-01-01

    Background In a rapidly changing world, it is of fundamental importance to understand processes constraining or facilitating adaptation through microevolution. As different traits of an organism covary, genetic correlations are expected to affect evolutionary trajectories. However, only limited empirical data are available. Methodology/Principal Findings We investigate the extent to which multivariate constraints affect the rate of adaptation, focusing on four morphological traits often shown to harbour large amounts of genetic variance and considered to be subject to limited evolutionary constraints. Our data set includes unique long-term data for seven bird species and a total of 10 populations. We estimate population-specific matrices of genetic correlations and multivariate selection coefficients to predict evolutionary responses to selection. Using Bayesian methods that facilitate the propagation of errors in estimates, we compare (1) the rate of adaptation based on predicted response to selection when including genetic correlations with predictions from models where these genetic correlations were set to zero and (2) the multivariate evolvability in the direction of current selection to the average evolvability in random directions of the phenotypic space. We show that genetic correlations on average decrease the predicted rate of adaptation by 28%. Multivariate evolvability in the direction of current selection was systematically lower than average evolvability in random directions of space. These significant reductions in the rate of adaptation and reduced evolvability were due to a general nonalignment of selection and genetic variance, notably orthogonality of directional selection with the size axis along which most (60%) of the genetic variance is found. Conclusions These results suggest that genetic correlations can impose significant constraints on the evolution of avian morphology in wild populations. This could have important impacts on evolutionary

  13. Simpler way of imposing simplicity constraints

    NASA Astrophysics Data System (ADS)

    Banburski, Andrzej; Chen, Lin-Qing

    2016-11-01

    We investigate a way of imposing simplicity constraints in a holomorphic spin foam model that we recently introduced. Rather than imposing the constraints on the boundary spin network, as is usually done, one can impose the constraints directly on the spin foam propagator. We find that the two approaches have the same leading asymptotic behavior, with differences appearing at higher order. This allows us to obtain a model that greatly simplifies calculations, but still has Regge calculus as its semiclassical limit.

  14. Initial value constraints with tensor matter

    NASA Astrophysics Data System (ADS)

    Jacobson, Ted

    2011-12-01

    In generally covariant metric gravity theories with tensor matter fields, the initial value constraint equations, unlike in general relativity, are in general not just the 0μ components of the metric field equation. This happens because higher derivatives can occur in the matter stress tensor. A universal form for these constraints is derived here from a generalized Bianchi identity that includes matter fields. As an application, the constraints for Einstein-aether theory are found.

  15. Geomagnetic main field modeling using magnetohydrodynamic constraints

    NASA Technical Reports Server (NTRS)

    Estes, R. H.

    1985-01-01

    The influence of physical constraints are investigated which may be approximately satisfied by the Earth's liquid core on models of the geomagnetic main field and its secular variation. A previous report describes the methodology used to incorporate nonlinear equations of constraint into the main field model. The application of that methodology to the GSFC 12/83 field model to test the frozen-flux hypothesis and the usefulness of incorporating magnetohydrodynamic constraints for obtaining improved geomagnetic field models is described.

  16. Direct-to-consumer genetic testing: an assessment of genetic counselors' knowledge and beliefs

    PubMed Central

    Hock, Kathryn T.; Christensen, Kurt D.; Yashar, Beverly M.; Roberts, J. Scott; Gollust, Sarah E.; Uhlmann, Wendy R.

    2013-01-01

    Purpose Direct-to-consumer genetic testing is a new means of obtaining genetic testing outside of a traditional clinical setting. This study assesses genetic counselors’ experience, knowledge, and beliefs regarding direct-to-consumer genetic testing for tests that would currently be offered in genetics clinics. Methods Members of the National Society of Genetic Counselors completed a web-administered survey in February 2008. Results Response rate was 36%; the final data analysis included 312 respondents. Eighty-three percent of respondents had two or fewer inquiries about direct-to-consumer genetic testing, and 14% had received requests for test interpretation or discussion. Respondents believed that genetic counselors have a professional obligation to be knowledgeable about direct-to-consumer genetic testing (55%) and interpret results (48%). Fifty-one percent of respondents thought genetic testing should be limited to a clinical setting; 56% agreed direct-to-consumer genetic testing is acceptable if genetic counseling is provided. More than 70% of respondents would definitely or possibly consider direct-to-consumer testing for patients who (1) have concerns about genetic discrimination, (2) want anonymous testing, or (3) have geographic constraints. Conclusions Results indicate that genetic counselors have limited patient experiences with direct-to-consumer genetic testing and are cautiously considering if and under what circumstances this approach should be used PMID:21233722

  17. Exploiting Constraints in Design Synthesis

    DTIC Science & Technology

    1987-04-01

    policy for a state. Herbert Simon , The Science of Design 1.1 Overview Robot planning, genetic synthesis, chemical synthesis, circuit design, and...Sanders Peirce (1839-1914) [36] used "abduction" to mean the "creative formulation of statistical hypotheses" (Encyclopedia of Philosophy, page 4-176... theory be part of the design. In short, there is a certain threshold of detail that is agreed upon by the designer and implementor as being primitively

  18. A Guide to the Field Guides.

    ERIC Educational Resources Information Center

    Natural History, 1987

    1987-01-01

    Provides a compilation of recommended field guides which deal with birds, mammals, trees, and wildflowers. Each recommended volume is described, noting its distinguishing features and evaluating its organization, photography, and text. Includes the author, publisher, and suggested retail price. (TW)

  19. Phylogeny of genetic codes and punctuation codes within genetic codes.

    PubMed

    Seligmann, Hervé

    2015-03-01

    Punctuation codons (starts, stops) delimit genes, reflect translation apparatus properties. Most codon reassignments involve punctuation. Here two complementary approaches classify natural genetic codes: (A) properties of amino acids assigned to codons (classical phylogeny), coding stops as X (A1, antitermination/suppressor tRNAs insert unknown residues), or as gaps (A2, no translation, classical stop); and (B) considering only punctuation status (start, stop and other codons coded as -1, 0 and 1 (B1); 0, -1 and 1 (B2, reflects ribosomal translational dynamics); and 1, -1, and 0 (B3, starts/stops as opposites)). All methods separate most mitochondrial codes from most nuclear codes; Gracilibacteria consistently cluster with metazoan mitochondria; mitochondria co-hosted with chloroplasts cluster with nuclear codes. Method A1 clusters the euplotid nuclear code with metazoan mitochondria; A2 separates euplotids from mitochondria. Firmicute bacteria Mycoplasma/Spiroplasma and Protozoan (and lower metazoan) mitochondria share codon-amino acid assignments. A1 clusters them with mitochondria, they cluster with the standard genetic code under A2: constraints on amino acid ambiguity versus punctuation-signaling produced the mitochondrial versus bacterial versions of this genetic code. Punctuation analysis B2 converges best with classical phylogenetic analyses, stressing the need for a unified theory of genetic code punctuation accounting for ribosomal constraints.

  20. Genetics Home Reference: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

    MedlinePlus

    ... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions CADASIL cerebral autosomal dominant arteriopathy ...

  1. Constraint-Directed Search: A Case Study of Job-Shop Scheduling.

    DTIC Science & Technology

    1983-12-13

    gap between scheduling systems which simply guide the human scheduler, to a scheduling system that can control operations in realtime. The rest of...ability, leaving much of the work to the human Eicheduler. In this section we will illustrate the nature of the scheduling problem and the constraints which...example, a left-leg is part of a human , or B-52 bombers are part of the nuclear defense triad. structure/sub-structure-of: It specifies a structuring

  2. Using Public-Private Partnerships to Mitigate Disparities in Access to Genetic Services: Lessons from Wisconsin

    PubMed Central

    Senier, Laura; Kearney, Matthew; Orne, Jason

    2016-01-01

    Purpose This mixed-methods study reports on an outreach clinics program designed to deliver genetic services to medically underserved communities in Wisconsin. Methodology We show the geographic distribution, funding patterns, and utilization trends for outreach clinics over a 20-year period. Interviews with program planners and outreach clinic staff show how external and internal constraints limited the program’s capacity. We compare clinic operations to the conceptual models guiding program design. Findings Our findings show that state health officials had to scale back financial support for outreach clinic activities while healthcare providers faced increasing pressure from administrators to reduce investments in charity care. These external and internal constraints led to a decline in the overall number of patients served. We also find that redistribution of clinics to the Milwaukee area increased utilization among Hispanics but not among African-Americans. Our interviews suggest that these patterns may be a function of shortcomings embedded in the planning models. Implications Planning models have three shortcomings. First, they do not identify the mitigation of health disparities as a specific goal. Second, they fail to acknowledge that partners face escalating profit-seeking mandates that may limit their capacity to provide charity services. Finally, they underemphasize the importance of seeking trusted partners, especially in working with communities that have been historically marginalized. Contribution There has been little discussion about equitably leveraging genetic advances that improve healthcare quality and efficacy. The role of State Health Agencies in mitigating disparities in access to genetic services has been largely ignored in the sociological literature. PMID:27279725

  3. Closed Loop Guidance with Multiple Constraints for Low Orbit Vehicle Trajectory Optimization

    NASA Astrophysics Data System (ADS)

    Zhang, Rufei; Zhao, Shifan

    Low orbit has features of strong invisibility and penetration, but needs more shutdown energy comparable to high orbit under the same range, which strongly requires studying the problem of delivery capacity optimization for multi-stage launch vehicles. Based on remnant apparent velocity and constraints models, multi-constraint closed-loop guidance with constraints of trajectory maximum height and azimuth was proposed, which adopted elliptical orbit theory and Newton iteration algorithm to optimize trajectory and thrust direction, reached to take full advantage of multi-stage launch vehicle propellant, and guided low orbit vehicle to enter maximum range trajectory. Theory deduction and numerical example demonstrate that the proposed guidance method could extend range and achieve precise control for orbit maximum height and azimuth.

  4. Learning Artificial Phonotactic Constraints: Time Course, Durability, and Relationship to Natural Constraints

    ERIC Educational Resources Information Center

    Taylor, Conrad F.; Houghton, George

    2005-01-01

    G. S. Dell, K. D. Reed, D. R. Adams, and A. S. Meyer (2000) proposed a "breadth-of-constraint" continuum on phoneme errors, using artificial experiment-wide constraints to investigate a putative middle ground between local and language-wide constraints. The authors report 5 experiments that test the idea of the continuum and the location of the…

  5. Learning Artificial Phonotactic Constraints: Time Course, Durability, and Relationship to Natural Constraints

    ERIC Educational Resources Information Center

    Taylor, Conrad F.; Houghton, George

    2005-01-01

    G. S. Dell, K. D. Reed, D. R. Adams, and A. S. Meyer (2000) proposed a "breadth-of-constraint" continuum on phoneme errors, using artificial experiment-wide constraints to investigate a putative middle ground between local and language-wide constraints. The authors report 5 experiments that test the idea of the continuum and the location of the…

  6. Phonological Constraint Induction in a Connectionist Network: Learning OCP-Place Constraints from Data

    ERIC Educational Resources Information Center

    Alderete, John; Tupper, Paul; Frisch, Stefan A.

    2013-01-01

    A significant problem in computational language learning is that of inferring the content of well-formedness constraints from input data. In this article, we approach the constraint induction problem as the gradual adjustment of subsymbolic constraints in a connectionist network. In particular, we develop a multi-layer feed-forward network that…

  7. Phonological Constraint Induction in a Connectionist Network: Learning OCP-Place Constraints from Data

    ERIC Educational Resources Information Center

    Alderete, John; Tupper, Paul; Frisch, Stefan A.

    2013-01-01

    A significant problem in computational language learning is that of inferring the content of well-formedness constraints from input data. In this article, we approach the constraint induction problem as the gradual adjustment of subsymbolic constraints in a connectionist network. In particular, we develop a multi-layer feed-forward network that…

  8. The Problem of Evolving a Genetic Code

    ERIC Educational Resources Information Center

    Woese, Carl R.

    1970-01-01

    Proposes models for the evolution of the genetic code and translation mechanisms. Suggests that the translation process is so complex and precise that it must have evolved in many stages, and that the evolution of the code was influenced by the constraints imposed by the evolving translation mechanism. (EB)

  9. Constraints on the symmetry noninheriting scalar black hole hair

    NASA Astrophysics Data System (ADS)

    Smolić, Ivica

    2017-01-01

    Any recipe to grow black hole hair has to circumvent no-hair theorems by violating some of their assumptions. Recently discovered hairy black hole solutions exist due to the fact that their scalar fields don't inherit the symmetries of the spacetime metric. We present here a general analysis of the constraints which limit the possible forms of such a hair, for both the real and the complex scalar fields. These results can be taken as a novel piece of the black hole uniqueness theorems or simply as a symmetry noninheriting Ansätze guide. In addition, we introduce new classification of the gravitational field equations which might prove useful for various generalizations of the theorems about spacetimes with symmetries.

  10. Trimodal interpretation of constraints for planning

    NASA Technical Reports Server (NTRS)

    Krieger, David; Brown, Richard

    1987-01-01

    Constraints are used in the CAMPS knowledge based planning system to represent those propositions that must be true for a plan to be acceptable. CAMPS introduces the make-mode for interpreting a constraint. Given an unsatisfied constraint, make evaluation mode suggests planning actions which, if taken, would result in a modified plan in which the constraint in question may be satisfied. These suggested planning actions, termed delta-tuples, are the raw material of intelligent plan repair. They are used both in debugging an almost-right plan and in replanning due to changing situations. Given a defective plan in which some set of constraints are violated, a problem solving strategy selects one or more constraints as a focus of attention. These selected constraints are evaluated in the make-mode to produce delta-tuples. The problem solving strategy then reviews the delta-tuples according to its application and problem-specific criteria to find the most acceptable change in terms of success likelihood and plan disruption. Finally, the problem solving strategy makes the suggested alteration to the plan and then rechecks constraints to find any unexpected consequences.

  11. Linear determining equations for differential constraints

    SciTech Connect

    Kaptsov, O V

    1998-12-31

    A construction of differential constraints compatible with partial differential equations is considered. Certain linear determining equations with parameters are used to find such differential constraints. They generalize the classical determining equations used in the search for admissible Lie operators. As applications of this approach equations of an ideal incompressible fluid and non-linear heat equations are discussed.

  12. CUTTING PLANE METHODS WITHOUT NESTED CONSTRAINT SETS

    DTIC Science & Technology

    General conditions are given for the convergence of a class of cutting -plane algorithms without requiring that the constraint sets for the... cutting -planes include that of Kelley and a generalization of that used by Zoutendisk and Veinott. For algorithms with nested constraint sets, these

  13. The "No Crossing Constraint" in Autosegmental Phonology.

    ERIC Educational Resources Information Center

    Coleman, John; Local, John

    A discussion of autosegmental phonology (AP), a theory of phonological representation that uses graphs rather than strings as the central data structure, considers its principal constraint, the "No Crossing Constraint" (NCC). The NCC is the statement that in a well-formed autosegmental diagram, lines of association may not cross. After…

  14. Domain General Constraints on Statistical Learning

    ERIC Educational Resources Information Center

    Thiessen, Erik D.

    2011-01-01

    All theories of language development suggest that learning is constrained. However, theories differ on whether these constraints arise from language-specific processes or have domain-general origins such as the characteristics of human perception and information processing. The current experiments explored constraints on statistical learning of…

  15. Training Neural Networks with Weight Constraints

    DTIC Science & Technology

    1993-03-01

    Hardware implementation of artificial neural networks imposes a variety of constraints. Finite weight magnitudes exist in both digital and analog...optimizing a network with weight constraints. Comparisons are made to the backpropagation training algorithm for networks with both unconstrained and hard-limited weight magnitudes. Neural networks , Analog, Digital, Stochastic

  16. On Noisy Extensions of Nonholonomic Constraints

    NASA Astrophysics Data System (ADS)

    Gay-Balmaz, François; Putkaradze, Vakhtang

    2016-12-01

    We propose several stochastic extensions of nonholonomic constraints for mechanical systems and study the effects on the dynamics and on the conservation laws. Our approach relies on a stochastic extension of the Lagrange-d'Alembert framework. The mechanical system we focus on is the example of a Routh sphere, i.e., a rolling unbalanced ball on the plane. We interpret the noise in the constraint as either a stochastic motion of the plane, random slip or roughness of the surface. Without the noise, this system possesses three integrals of motion: energy, Jellet and Routh. Depending on the nature of noise in the constraint, we show that either energy, or Jellet, or both integrals can be conserved, with probability 1. We also present some exact solutions for particular types of motion in terms of stochastic integrals. Next, for an arbitrary nonholonomic system, we consider two different ways of including stochasticity in the constraints. We show that when the noise preserves the linearity of the constraints, then energy is preserved. For other types of noise in the constraint, e.g., in the case of an affine noise, the energy is not conserved. We study in detail a class of Lagrangian mechanical systems on semidirect products of Lie groups, with "rolling ball type" constraints. We conclude with numerical simulations illustrating our theories, and some pedagogical examples of noise in constraints for other nonholonomic systems popular in the literature, such as the nonholonomic particle, the rolling disk and the Chaplygin sleigh.

  17. COSMOLOGICAL CONSTRAINTS FROM GRAVITATIONAL LENS TIME DELAYS

    SciTech Connect

    Coe, Dan; Moustakas, Leonidas A.

    2009-11-20

    Future large ensembles of time delay (TD) lenses have the potential to provide interesting cosmological constraints complementary to those of other methods. In a flat universe with constant w including a Planck prior, The Large Synoptic Survey Telescope TD measurements for approx4000 lenses should constrain the local Hubble constant h to approx0.007 (approx1%), OMEGA{sub de} to approx0.005, and w to approx0.026 (all 1sigma precisions). Similar constraints could be obtained by a dedicated gravitational lens observatory (OMEGA) which would obtain precise TD and mass model measurements for approx100 well-studied lenses. We compare these constraints (as well as those for a more general cosmology) to the 'optimistic Stage IV' constraints expected from weak lensing, supernovae, baryon acoustic oscillations, and cluster counts, as calculated by the Dark Energy Task Force. TDs yield a modest constraint on a time-varying w(z), with the best constraint on w(z) at the 'pivot redshift' of z approx 0.31. Our Fisher matrix calculation is provided to allow TD constraints to be easily compared to and combined with constraints from other experiments. We also show how cosmological constraining power varies as a function of numbers of lenses, lens model uncertainty, TD precision, redshift precision, and the ratio of four-image to two-image lenses.

  18. The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: promise of molecular genetics for guiding mechanistic and translational research in the field1234

    PubMed Central

    Neuringer, Martha

    2012-01-01

    Age-related macular degeneration (AMD) is the primary cause of vision loss in elderly people of western European ancestry. Genetic, dietary, and environmental factors affect tissue concentrations of macular xanthophylls (MXs) within retinal cell types manifesting AMD pathology. In this article we review the history and state of science on the putative role of the MXs (lutein, zeaxanthin, and meso-zeaxanthin) in AMD and report findings on AMD-associated genes encoding enzymes, transporters, ligands, and receptors affecting or affected by MXs. We then use this context to discuss emerging research opportunities that offer promise for meaningful investigation and inference in the field. PMID:23053548

  19. Genetic Testing in Pediatric Ophthalmology.

    PubMed

    Verma, Ishwar Chander; Paliwal, Preeti; Singh, Kanika

    2017-10-02

    The authors review the utility of genetic testing in ophthalmic disorders - precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pre-test and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed - anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.

  20. Sex reduces genetic variation: a multidisciplinary review.

    PubMed

    Gorelick, Root; Heng, Henry H Q

    2011-04-01

    For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence for sex decreasing genetic variation appears in ecology, paleontology, population genetics, and cancer biology. The common thread among many of these disciplines is that sex acts like a coarse filter, weeding out major changes, such as chromosomal rearrangements (that are almost always deleterious), but letting minor variation, such as changes at the nucleotide or gene level (that are often neutral), flow through the sexual sieve. Sex acts as a constraint on genomic and epigenetic variation, thereby limiting adaptive evolution. The diverse reasons for sex reducing genetic variation (especially at the genome level) and slowing down evolution may provide a sufficient benefit to offset the famed costs of sex.

  1. Constraints, histones, and the 30-nm spiral

    NASA Astrophysics Data System (ADS)

    Zandi, Roya; Rudnick, Joseph

    2001-11-01

    We investigate the mechanical stability of a segment of DNA wrapped around a histone in the nucleosome configuration, under the assumption that the proper model for this packaging arrangement is that of an elastic rod that is free to twist and that writhes subject to mechanical constraints. We find that the number of constraints required to stabilize the nuclesome configuration is determined by the length of the segment, the number of times the DNA wraps around the histone spool, and the specific constraints utilized. While it can be shown that four constraints suffice, in principle, to insure stability of the nucleosome, a proper choice must be made to guarantee the effectiveness of this minimal number. The optimal choice of constraints appears to bear a relation to the existence of a spiral ridge on the surface of the histone octamer. The particular configuration that we investigate is related to the 30-nm spiral, a higher-order organization of DNA in chromatin.

  2. Solar system constraints on disformal gravity theories

    SciTech Connect

    Ip, Hiu Yan; Schmidt, Fabian; Sakstein, Jeremy E-mail: jeremy.sakstein@port.ac.uk

    2015-10-01

    Disformal theories of gravity are scalar-tensor theories where the scalar couples derivatively to matter via the Jordan frame metric. These models have recently attracted interest in the cosmological context since they admit accelerating solutions. We derive the solution for a static isolated mass in generic disformal gravity theories and transform it into the parameterised post-Newtonian form. This allows us to investigate constraints placed on such theories by local tests of gravity. The tightest constraints come from preferred-frame effects due to the motion of the Solar System with respect to the evolving cosmological background field. The constraints we obtain improve upon the previous solar system constraints by two orders of magnitude, and constrain the scale of the disformal coupling for generic models to ℳ ∼> 100 eV. These constraints render all disformal effects irrelevant for cosmology.

  3. Linear predictive control with state variable constraints

    NASA Astrophysics Data System (ADS)

    Bdirina, K.; Djoudi, D.; Lagoun, M.

    2012-11-01

    While linear model predictive control is popular since the 70s of the past century, the 90s have witnessed a steadily increasing attention from control theoretists as well as control practitioners in the area of model predictive control (MPC). The practical interest is driven by the fact that today's processes need to be operated under tighter performance specifications. At the same time more and more constraints, stemming for example from environmental and safety considerations, need to besatisfied. Often these demands can only be met when process constraints are explicitly considered in the controller. Predictive control with constraints appears to be a well suited approach for this kind of problems. In this paper the basic principle of MPC with constraints is reviewed and some of the theoretical, computational, and implementation aspects of MPC are discussed. Furthermore the MPC with constraints was applied to linear example.

  4. Volcanological constraints of Archaean tectonics

    NASA Technical Reports Server (NTRS)

    Thurston, P. C.; Ayres, L. D.

    1986-01-01

    Volcanological and trace element geochemical data can be integrated to place some constraints upon the size, character and evolutionary history of Archean volcanic plumbing, and hence indirectly, Archean tectonics. The earliest volcanism in any greenhouse belt is almost universally tholeitic basalt. Archean mafic magma chambers were usually the site of low pressure fractionation of olivine, plagioclase and later Cpx + or - an oxide phase during evolution of tholeitic liquids. Several models suggest basalt becoming more contaminated by sial with time. Data in the Uchi Subprovince shows early felsic volcanics to have fractionated REE patterns followed by flat REE pattern rhyolites. This is interpreted as initial felsic liquids produced by melting of a garnetiferous mafic source followed by large scale melting of LIL-rich sial. Rare andesites in the Uchi Subprovince are produced by basalt fractionation, direct mantle melts and mixing of basaltic and tonalitic liquids. Composite dikes in the Abitibi Subprovince have a basaltic edge with a chill margin, a rhyolitic interior with no basalt-rhyolite chill margin and partially melted sialic inclusions. Ignimbrites in the Uchi and Abitibi Subprovinces have mafic pumice toward the top. Integration of these data suggest initial mantle-derived basaltic liquids pond in a sialic crust, fractionate and melt sial. The inirial melts low in heavy REE are melts of mafic material, subsequently melting of adjacent sial produces a chamber with a felsic upper part underlain by mafic magma.

  5. Developmental constraints in cave beetles.

    PubMed

    Cieslak, Alexandra; Fresneda, Javier; Ribera, Ignacio

    2014-10-01

    In insects, whilst variations in life cycles are common, the basic patterns typical for particular groups remain generally conserved. One of the more extreme modifications is found in some subterranean beetles of the tribe Leptodirini, in which the number of larval instars is reduced from the ancestral three to two and ultimately one, which is not active and does not feed. We analysed all available data on the duration and size of the different developmental stages and compared them in a phylogenetic context. The total duration of development was found to be strongly conserved, irrespective of geographical location, habitat type, number of instars and feeding behaviour of the larvae, with a single alteration of the developmental pattern in a clade of cave species in southeast France. We also found a strong correlation of the size of the first instar larva with adult size, again regardless of geographical location, ecology and type of life cycle. Both results suggest the presence of deeply conserved constraints in the timing and energy requirements of larval development. Past focus on more apparent changes, such as the number of larval instars, may mask more deeply conserved ontogenetic patterns in developmental timing. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  6. Developmental constraints in cave beetles

    PubMed Central

    Cieslak, Alexandra; Fresneda, Javier; Ribera, Ignacio

    2014-01-01

    In insects, whilst variations in life cycles are common, the basic patterns typical for particular groups remain generally conserved. One of the more extreme modifications is found in some subterranean beetles of the tribe Leptodirini, in which the number of larval instars is reduced from the ancestral three to two and ultimately one, which is not active and does not feed. We analysed all available data on the duration and size of the different developmental stages and compared them in a phylogenetic context. The total duration of development was found to be strongly conserved, irrespective of geographical location, habitat type, number of instars and feeding behaviour of the larvae, with a single alteration of the developmental pattern in a clade of cave species in southeast France. We also found a strong correlation of the size of the first instar larva with adult size, again regardless of geographical location, ecology and type of life cycle. Both results suggest the presence of deeply conserved constraints in the timing and energy requirements of larval development. Past focus on more apparent changes, such as the number of larval instars, may mask more deeply conserved ontogenetic patterns in developmental timing. PMID:25354919

  7. Perceptual constraints in phonotactic learning.

    PubMed

    Endress, Ansgar D; Mehler, Jacques

    2010-02-01

    Structural regularities in language have often been attributed to symbolic or statistical general purpose computations, whereas perceptual factors influencing such generalizations have received less interest. Here, we use phonotactic-like constraints as a case study to ask whether the structural properties of specific perceptual and memory mechanisms may facilitate the acquisition of grammatical-like regularities. Participants learned that the consonants C and C had to come from distinct sets in words of the form CVccVC (where the critical consonants were in word edges) but not in words of the form cVCCVc (where the critical consonants were in word middles). Control conditions ruled out attentional or psychophysical difficulties in word middles. Participants did, however, learn such regularities in word middles when natural consonant classes were used instead of arbitrary consonant sets. We conclude that positional generalizations may be learned preferentially using edge-based positional codes, but that participants can also use other mechanisms when other linguistic cues are given.

  8. Percolation of spatially constraint networks

    NASA Astrophysics Data System (ADS)

    Li, Daqing; Li, Guanliang; Kosmidis, Kosmas; Stanley, H. E.; Bunde, Armin; Havlin, Shlomo

    2011-03-01

    We study how spatial constraints are reflected in the percolation properties of networks embedded in one-dimensional chains and two-dimensional lattices. We assume long-range connections between sites on the lattice where two sites at distance r are chosen to be linked with probability p(r)~r-δ. Similar distributions have been found in spatially embedded real networks such as social and airline networks. We find that for networks embedded in two dimensions, with 2<δ<4, the percolation properties show new intermediate behavior different from mean field, with critical exponents that depend on δ. For δ<2, the percolation transition belongs to the universality class of percolation in Erdös-Rényi networks (mean field), while for δ>4 it belongs to the universality class of percolation in regular lattices. For networks embedded in one dimension, we find that, for δ<1, the percolation transition is mean field. For 1<δ<2, the critical exponents depend on δ, while for δ>2 there is no percolation transition as in regular linear chains.

  9. Optimal Stopping with Information Constraint

    SciTech Connect

    Lempa, Jukka

    2012-10-15

    We study the optimal stopping problem proposed by Dupuis and Wang (Adv. Appl. Probab. 34:141-157, 2002). In this maximization problem of the expected present value of the exercise payoff, the underlying dynamics follow a linear diffusion. The decision maker is not allowed to stop at any time she chooses but rather on the jump times of an independent Poisson process. Dupuis and Wang (Adv. Appl. Probab. 34:141-157, 2002), solve this problem in the case where the underlying is a geometric Brownian motion and the payoff function is of American call option type. In the current study, we propose a mild set of conditions (covering the setup of Dupuis and Wang in Adv. Appl. Probab. 34:141-157, 2002) on both the underlying and the payoff and build and use a Markovian apparatus based on the Bellman principle of optimality to solve the problem under these conditions. We also discuss the interpretation of this model as optimal timing of an irreversible investment decision under an exogenous information constraint.

  10. Hamiltonian constraint in polymer parametrized field theory

    NASA Astrophysics Data System (ADS)

    Laddha, Alok; Varadarajan, Madhavan

    2011-01-01

    Recently, a generally covariant reformulation of two-dimensional flat spacetime free scalar field theory known as parametrized field theory was quantized using loop quantum gravity (LQG) type “polymer” representations. Physical states were constructed, without intermediate regularization structures, by averaging over the group of gauge transformations generated by the constraints, the constraint algebra being a Lie algebra. We consider classically equivalent combinations of these constraints corresponding to a diffeomorphism and a Hamiltonian constraint, which, as in gravity, define a Dirac algebra. Our treatment of the quantum constraints parallels that of LQG and obtains the following results, expected to be of use in the construction of the quantum dynamics of LQG: (i) the (triangulated) Hamiltonian constraint acts only on vertices, its construction involves some of the same ambiguities as in LQG and its action on diffeomorphism invariant states admits a continuum limit, (ii) if the regulating holonomies are in representations tailored to the edge labels of the state, all previously obtained physical states lie in the kernel of the Hamiltonian constraint, (iii) the commutator of two (density weight 1) Hamiltonian constraints as well as the operator correspondent of their classical Poisson bracket converge to zero in the continuum limit defined by diffeomorphism invariant states, and vanish on the Lewandowski-Marolf habitat, (iv) the rescaled density 2 Hamiltonian constraints and their commutator are ill-defined on the Lewandowski-Marolf habitat despite the well-definedness of the operator correspondent of their classical Poisson bracket there, (v) there is a new habitat which supports a nontrivial representation of the Poisson-Lie algebra of density 2 constraints.

  11. Hamiltonian constraint in polymer parametrized field theory

    SciTech Connect

    Laddha, Alok; Varadarajan, Madhavan

    2011-01-15

    Recently, a generally covariant reformulation of two-dimensional flat spacetime free scalar field theory known as parametrized field theory was quantized using loop quantum gravity (LQG) type ''polymer'' representations. Physical states were constructed, without intermediate regularization structures, by averaging over the group of gauge transformations generated by the constraints, the constraint algebra being a Lie algebra. We consider classically equivalent combinations of these constraints corresponding to a diffeomorphism and a Hamiltonian constraint, which, as in gravity, define a Dirac algebra. Our treatment of the quantum constraints parallels that of LQG and obtains the following results, expected to be of use in the construction of the quantum dynamics of LQG: (i) the (triangulated) Hamiltonian constraint acts only on vertices, its construction involves some of the same ambiguities as in LQG and its action on diffeomorphism invariant states admits a continuum limit, (ii) if the regulating holonomies are in representations tailored to the edge labels of the state, all previously obtained physical states lie in the kernel of the Hamiltonian constraint, (iii) the commutator of two (density weight 1) Hamiltonian constraints as well as the operator correspondent of their classical Poisson bracket converge to zero in the continuum limit defined by diffeomorphism invariant states, and vanish on the Lewandowski-Marolf habitat, (iv) the rescaled density 2 Hamiltonian constraints and their commutator are ill-defined on the Lewandowski-Marolf habitat despite the well-definedness of the operator correspondent of their classical Poisson bracket there, (v) there is a new habitat which supports a nontrivial representation of the Poisson-Lie algebra of density 2 constraints.

  12. OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

    PubMed Central

    Bradley, Kevin M

    2014-01-01

    Summary Synthetic biologists wishing to self-assemble large DNA (L-DNA) constructs from small DNA fragments made by automated synthesis need fragments that hybridize predictably. Such predictability is difficult to obtain with nucleotides built from just the four standard nucleotides. Natural DNA's peculiar combination of strong and weak G:C and A:T pairs, the context-dependence of the strengths of those pairs, unimolecular strand folding that competes with desired interstrand hybridization, and non-Watson–Crick interactions available to standard DNA, all contribute to this unpredictability. In principle, adding extra nucleotides to the genetic alphabet can improve the predictability and reliability of autonomous DNA self-assembly, simply by increasing the information density of oligonucleotide sequences. These extra nucleotides are now available as parts of artificially expanded genetic information systems (AEGIS), and tools are now available to generate entirely standard DNA from AEGIS DNA during PCR amplification. Here, we describe the OligArch (for "oligonucleotide architecting") software, an application that permits synthetic biologists to engineer optimally self-assembling DNA constructs from both six- and eight-letter AEGIS alphabets. This software has been used to design oligonucleotides that self-assemble to form complete genes from 20 or more single-stranded synthetic oligonucleotides. OligArch is therefore a key element of a scalable and integrated infrastructure for the rapid and designed engineering of biology. PMID:25161743

  13. An ecologist's guide to the animal model.

    PubMed

    Wilson, Alastair J; Réale, Denis; Clements, Michelle N; Morrissey, Michael M; Postma, Erik; Walling, Craig A; Kruuk, Loeske E B; Nussey, Daniel H

    2010-01-01

    1. Efforts to understand the links between evolutionary and ecological dynamics hinge on our ability to measure and understand how genes influence phenotypes, fitness and population dynamics. Quantitative genetics provides a range of theoretical and empirical tools with which to achieve this when the relatedness between individuals within a population is known. 2. A number of recent studies have used a type of mixed-effects model, known as the animal model, to estimate the genetic component of phenotypic variation using data collected in the field. Here, we provide a practical guide for ecologists interested in exploring the potential to apply this quantitative genetic method in their research. 3. We begin by outlining, in simple terms, key concepts in quantitative genetics and how an animal model estimates relevant quantitative genetic parameters, such as heritabilities or genetic correlations. 4. We then provide three detailed example tutorials, for implementation in a variety of software packages, for some basic applications of the animal model. We discuss several important statistical issues relating to best practice when fitting different kinds of mixed models. 5. We conclude by briefly summarizing more complex applications of the animal model, and by highlighting key pitfalls and dangers for the researcher wanting to begin using quantitative genetic tools to address ecological and evolutionary questions.

  14. Genetic barcodes

    DOEpatents

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  15. Sensor Characteristics Reference Guide

    SciTech Connect

    none,

    2013-04-01

    The purpose of the guide is to inform building owners and operators of the current status, capabilities, and limitations of sensor technologies. It is hoped that this guide will aid in the design and procurement process and result in successful implementation of building sensor and control systems. DOE will also use this guide to identify research priorities, develop future specifications for potential market adoption, and provide market clarity through unbiased information.

  16. XML Style Guide

    DTIC Science & Technology

    2015-07-01

    TELEMETRY GROUP DOCUMENT 125-15 XML STYLE GUIDE DISTRIBUTION A: APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED...OMB control number. 1. REPORT DATE 01 JUL 2015 2. REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE XML Style Guide 5a. CONTRACT...standard was prepared by the Data Multiplex Committee of the Telemetry Group, Range Commanders Council. The XML Style Guide defines rules and guidelines

  17. Relativistic Guiding Center Equations

    SciTech Connect

    White, R. B.; Gobbin, M.

    2014-10-01

    In toroidal fusion devices it is relatively easy that electrons achieve relativistic velocities, so to simulate runaway electrons and other high energy phenomena a nonrelativistic guiding center formalism is not sufficient. Relativistic guiding center equations including flute mode time dependent field perturbations are derived. The same variables as used in a previous nonrelativistic guiding center code are adopted, so that a straightforward modifications of those equations can produce a relativistic version.

  18. Fundamental Activity Constraints Lead to Specific Interpretations of the Connectome

    PubMed Central

    van Albada, Sacha J.; Diesmann, Markus; Helias, Moritz

    2017-01-01

    The continuous integration of experimental data into coherent models of the brain is an increasing challenge of modern neuroscience. Such models provide a bridge between structure and activity, and identify the mechanisms giving rise to experimental observations. Nevertheless, structurally realistic network models of spiking neurons are necessarily underconstrained even if experimental data on brain connectivity are incorporated to the best of our knowledge. Guided by physiological observations, any model must therefore explore the parameter ranges within the uncertainty of the data. Based on simulation results alone, however, the mechanisms underlying stable and physiologically realistic activity often remain obscure. We here employ a mean-field reduction of the dynamics, which allows us to include activity constraints into the process of model construction. We shape the phase space of a multi-scale network model of the vision-related areas of macaque cortex by systematically refining its connectivity. Fundamental constraints on the activity, i.e., prohibiting quiescence and requiring global stability, prove sufficient to obtain realistic layer- and area-specific activity. Only small adaptations of the structure are required, showing that the network operates close to an instability. The procedure identifies components of the network critical to its collective dynamics and creates hypotheses for structural data and future experiments. The method can be applied to networks involving any neuron model with a known gain function. PMID:28146554

  19. Genetic Alliance

    MedlinePlus

    ... educate consumers around appropriate testing and public health services, and help individuals navigate the complex health care delivery system. Highlights Genetic Alliance Internship Program Learn about ...

  20. Phytoremediation Resource Guide

    EPA Pesticide Factsheets

    This Guide provides abstracts of over 100 phytoremediation overviews, field studies and demonstrations, research articles, and Internet resources. It also provides a brief summary of phytoremediation.

  1. Precision guided antiaircraft munition

    DOEpatents

    Hirschfeld, Tomas B.

    1987-01-01

    A small diameter, 20 mm to 50 mm, guided projectile is used in antiaircraft defense. A pulsing laser designator illuminates the target aircraft. Energy reflected from the aircraft is received by the guided projectile. The guided projectile is fired from a standard weapon but the spining caused by the riflings are removed before active tracking and guidance occurs. The received energy is focused by immersion optics onto a bridge cell. AC coupling and gating removes background and allows steering signals to move extended vanes by means of piezoelectric actuators in the rear of the guided projectile.

  2. Find the weakest link. A comparison between demographic, genetic and demo-genetic metapopulation extinction times

    PubMed Central

    2011-01-01

    Background While the ultimate causes of most species extinctions are environmental, environmental constraints have various secondary consequences on evolutionary and ecological processes. The roles of demographic, genetic mechanisms and their interactions in limiting the viabilities of species or populations have stirred much debate and remain difficult to evaluate in the absence of demography-genetics conceptual and technical framework. Here, I computed projected times to metapopulation extinction using (1) a model focusing on the effects of species properties, habitat quality, quantity and temporal variability on the time to demographic extinction; (2) a genetic model focusing on the dynamics of the drift and inbreeding loads under the same species and habitat constraints; (3) a demo-genetic model accounting for demographic-genetic processes and feedbacks. Results Results indicate that a given population may have a high demographic, but low genetic viability or vice versa; and whether genetic or demographic aspects will be the most limiting to overall viability depends on the constraints faced by the species (e.g., reduction of habitat quantity or quality). As a consequence, depending on metapopulation or species characteristics, incorporating genetic considerations to demographically-based viability assessments may either moderately or severely reduce the persistence time. On the other hand, purely genetically-based estimates of species viability may either underestimate (by neglecting demo-genetic interactions) or overestimate (by neglecting the demographic resilience) true viability. Conclusion Unbiased assessments of the viabilities of species may only be obtained by identifying and considering the most limiting processes (i.e., demography or genetics), or, preferentially, by integrating them. PMID:21929788

  3. Find the weakest link. A comparison between demographic, genetic and demo-genetic metapopulation extinction times.

    PubMed

    Robert, Alexandre

    2011-09-19

    While the ultimate causes of most species extinctions are environmental, environmental constraints have various secondary consequences on evolutionary and ecological processes. The roles of demographic, genetic mechanisms and their interactions in limiting the viabilities of species or populations have stirred much debate and remain difficult to evaluate in the absence of demography-genetics conceptual and technical framework. Here, I computed projected times to metapopulation extinction using (1) a model focusing on the effects of species properties, habitat quality, quantity and temporal variability on the time to demographic extinction; (2) a genetic model focusing on the dynamics of the drift and inbreeding loads under the same species and habitat constraints; (3) a demo-genetic model accounting for demographic-genetic processes and feedbacks. Results indicate that a given population may have a high demographic, but low genetic viability or vice versa; and whether genetic or demographic aspects will be the most limiting to overall viability depends on the constraints faced by the species (e.g., reduction of habitat quantity or quality). As a consequence, depending on metapopulation or species characteristics, incorporating genetic considerations to demographically-based viability assessments may either moderately or severely reduce the persistence time. On the other hand, purely genetically-based estimates of species viability may either underestimate (by neglecting demo-genetic interactions) or overestimate (by neglecting the demographic resilience) true viability. Unbiased assessments of the viabilities of species may only be obtained by identifying and considering the most limiting processes (i.e., demography or genetics), or, preferentially, by integrating them.

  4. Evolutionary constraints and the neutral theory. [mutation-caused nucleotide substitutions in DNA

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.; Kimura, M.

    1984-01-01

    The neutral theory of molecular evolution postulates that nucleotide substitutions inherently take place in DNA as a result of point mutations followed by random genetic drift. In the absence of selective constraints, the substitution rate reaches the maximum value set by the mutation rate. The rate in globin pseudogenes is about 5 x 10 to the -9th substitutions per site per year in mammals. Rates slower than this indicate the presence of constraints imposed by negative (natural) selection, which rejects and discards deleterious mutations.

  5. Evolutionary constraints and the neutral theory. [mutation-caused nucleotide substitutions in DNA

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.; Kimura, M.

    1984-01-01

    The neutral theory of molecular evolution postulates that nucleotide substitutions inherently take place in DNA as a result of point mutations followed by random genetic drift. In the absence of selective constraints, the substitution rate reaches the maximum value set by the mutation rate. The rate in globin pseudogenes is about 5 x 10 to the -9th substitutions per site per year in mammals. Rates slower than this indicate the presence of constraints imposed by negative (natural) selection, which rejects and discards deleterious mutations.

  6. Guide star targeting success for the HEAO-B observatory

    NASA Technical Reports Server (NTRS)

    Farrenkopf, R. L.; Hoffman, D. P.

    1977-01-01

    The statistics associated with the successful selection and acquisition of guide stars as attitude benchmarks for use in reorientation maneuvers of the HEAO-B observatory are considered as a function of the maneuver angle, initial attitude uncertainties, and the pertinent celestial region. Success likelihoods in excess of 0.99 are predicted assuming anticipated gyro and star tracker error sources. The maneuver technique and guide star selection constraints are described in detail. The results presented are specialized numerically to the HEAO-B observatory. However, the analytical techniques developed are considered applicable to broader classes of spacecraft requiring celestial targeting.

  7. Promoting integration of genetics core competencies into entry-level nursing curricula.

    PubMed

    Read, Catherine Y; Dylis, Ann M; Mott, Sandra R; Fairchild, Nancy J

    2004-08-01

    Nurse educators must respond to the growing need to teach genetics content in undergraduate nursing curricula. Recently developed genetics core competencies can be used to guide curriculum assessment and planning. This article describes a 5-year effort to integrate genetics education into a baccalaureate nursing curriculum and provides the results of a curriculum survey based on published genetics core competencies.

  8. Natural Constraints to Species Diversification

    PubMed Central

    Lewitus, Eric; Morlon, Hélène

    2016-01-01

    Identifying modes of species diversification is fundamental to our understanding of how biodiversity changes over evolutionary time. Diversification modes are captured in species phylogenies, but characterizing the landscape of diversification has been limited by the analytical tools available for directly comparing phylogenetic trees of groups of organisms. Here, we use a novel, non-parametric approach and 214 family-level phylogenies of vertebrates representing over 500 million years of evolution to identify major diversification modes, to characterize phylogenetic space, and to evaluate the bounds and central tendencies of species diversification. We identify five principal patterns of diversification to which all vertebrate families hold. These patterns, mapped onto multidimensional space, constitute a phylogenetic space with distinct properties. Firstly, phylogenetic space occupies only a portion of all possible tree space, showing family-level phylogenies to be constrained to a limited range of diversification patterns. Secondly, the geometry of phylogenetic space is delimited by quantifiable trade-offs in tree size and the heterogeneity and stem-to-tip distribution of branching events. These trade-offs are indicative of the instability of certain diversification patterns and effectively bound speciation rates (for successful clades) within upper and lower limits. Finally, both the constrained range and geometry of phylogenetic space are established by the differential effects of macroevolutionary processes on patterns of diversification. Given these properties, we show that the average path through phylogenetic space over evolutionary time traverses several diversification stages, each of which is defined by a different principal pattern of diversification and directed by a different macroevolutionary process. The identification of universal patterns and natural constraints to diversification provides a foundation for understanding the deep-time evolution of

  9. Natural Constraints to Species Diversification.

    PubMed

    Lewitus, Eric; Morlon, Hélène

    2016-08-01

    Identifying modes of species diversification is fundamental to our understanding of how biodiversity changes over evolutionary time. Diversification modes are captured in species phylogenies, but characterizing the landscape of diversification has been limited by the analytical tools available for directly comparing phylogenetic trees of groups of organisms. Here, we use a novel, non-parametric approach and 214 family-level phylogenies of vertebrates representing over 500 million years of evolution to identify major diversification modes, to characterize phylogenetic space, and to evaluate the bounds and central tendencies of species diversification. We identify five principal patterns of diversification to which all vertebrate families hold. These patterns, mapped onto multidimensional space, constitute a phylogenetic space with distinct properties. Firstly, phylogenetic space occupies only a portion of all possible tree space, showing family-level phylogenies to be constrained to a limited range of diversification patterns. Secondly, the geometry of phylogenetic space is delimited by quantifiable trade-offs in tree size and the heterogeneity and stem-to-tip distribution of branching events. These trade-offs are indicative of the instability of certain diversification patterns and effectively bound speciation rates (for successful clades) within upper and lower limits. Finally, both the constrained range and geometry of phylogenetic space are established by the differential effects of macroevolutionary processes on patterns of diversification. Given these properties, we show that the average path through phylogenetic space over evolutionary time traverses several diversification stages, each of which is defined by a different principal pattern of diversification and directed by a different macroevolutionary process. The identification of universal patterns and natural constraints to diversification provides a foundation for understanding the deep-time evolution of

  10. Hydrogeologic Constraints on Yucatan's Development.

    PubMed

    Doehring, D O; Butler, J H

    1974-11-15

    The Republic of Mexico has an ambitious and effective national water program. The Secretaria de Recursos Hidraulicos (SRH), whose director has cabinet rank in the federal government, is one of the most professionally distinguished government agencies of its kind in the Americas. Resources for the Future, Inc., has been assisting the World Bank with a water planning study which the Bank is undertaking jointly with the Mexican government. The study is intended to provide guidelines for the development of government policies and projects designed to bring about the most efficient use of Mexico's water resources. However, to date, their study has not been directed toward the growing problems of the northern Yucatáan Peninsula which are discussed here. LeGrand (13) suggested that man has inherited a harsh environment in carbonate terranes. In the case of the northern Yucatán Peninsula, the physical environment creates a set of hydrogeologic constraints to future economic and social development. Planning for intermediate and long-range land use on the peninsula must be related directly to the limited and fragile groundwater source. Continued contamination will make future aquifer management a difficult challenge for federal, state, and territorial agencies. We conclude that any strategy for long-range land use in the study area should include establishment of a regional aquifermonitoring network for long-term measurements of key hydrogeologic parameters, including precipitation, evapotranspiration, water table elevations, and water quality. Information from this network would flow into a central facility for storage, interpretation, and analysis. At present the SRH is collecting some of these data. Expansion of the existing program to provide sound information for regional planning will greatly benefit present as well as future generations. If such a program is implemented, it will represent a model for regional planning in other tropical and subtropical karstic

  11. An introductory review of parallel independent component analysis (p-ICA) and a guide to applying p-ICA to genetic data and imaging phenotypes to identify disease-associated biological pathways and systems in common complex disorders

    PubMed Central

    Pearlson, Godfrey D.; Liu, Jingyu; Calhoun, Vince D.

    2015-01-01

    Complex inherited phenotypes, including those for many common medical and psychiatric diseases, are most likely underpinned by multiple genes contributing to interlocking molecular biological processes, along with environmental factors (Owen et al., 2010). Despite this, genotyping strategies for complex, inherited, disease-related phenotypes mostly employ univariate analyses, e.g., genome wide association. Such procedures most often identify isolated risk-related SNPs or loci, not the underlying biological pathways necessary to help guide the development of novel treatment approaches. This article focuses on the multivariate analysis strategy of parallel (i.e., simultaneous combination of SNP and neuroimage information) independent component analysis (p-ICA), which typically yields large clusters of functionally related SNPs statistically correlated with phenotype components, whose overall molecular biologic relevance is inferred subsequently using annotation software suites. Because this is a novel approach, whose details are relatively new to the field we summarize its underlying principles and address conceptual questions regarding interpretation of resulting data and provide practical illustrations of the method. PMID:26442095

  12. Genetic Engineering

    ERIC Educational Resources Information Center

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  13. Genetic algorithms

    SciTech Connect

    Grefenstette, J.J.

    1994-12-31

    Genetic algorithms solve problems by using principles inspired by natural population genetics: They maintain a population of knowledge structures that represent candidate solutions, and then let that population evolve over time through competition and controlled variation. GAs are being applied to a wide range of optimization and learning problems in many domains.

  14. Genetic Counseling.

    ERIC Educational Resources Information Center

    Exceptional Parent, 1987

    1987-01-01

    Information is presented on a number of tests used in genetic counseling (e.g., genetic evaluation, chromosome evaluation, consideration of multifactorial conditions, prenatal testing, and chorionic villus sampling) which help parents with one disabled child make family planning decisions. (CB)

  15. Genetic Engineering

    ERIC Educational Resources Information Center

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  16. Genetic principles

    Treesearch

    Ronald P. Overton; David T. Funk

    1989-01-01

    Tree growth is a function of both environment and genetic makeup. All forest management activities during a rotation from establishment to harvest affect the genetic composition and the environment of a stand. Silvicultural practices which fail to take both of these factors into account will reduce forest productivity.

  17. Science: Grade 3. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  18. Science: Grade 6. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  19. Science: Grade 8. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  20. Science: Grade 5. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  1. Science: Grade 4. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  2. Science: Grade 2. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  3. Science: Grade 9. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  4. Science: Grade 3. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  5. Science: Grade 7. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  6. Science: Grade 7. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  7. Science: Grade 8. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  8. Science: Grade 5. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  9. Science: Grade 6. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  10. Science: Grade 9. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  11. Science: Grade 1. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is one of a set of 10 science guides, each covering a separate grade in Manitoba, together covering kindergarten through grade 9. The guides have been designed to provide a framework for building scientific concepts and developing the learning of process skills. They replace an earlier set of guides dated 1979. Each guide is essentially…

  12. CONSTRAINT EFFECT IN FRACTURE WHAT IS IT

    SciTech Connect

    Lam, P; Prof. Yuh J. Chao, P

    2008-10-29

    The meaning of the phrase 'constraint effect in fracture' has changed in the past two decades from 'contained plasticity' to a broader description of 'dependence of fracture toughness value on geometry of test specimen or structure'. This paper will first elucidate the fundamental mechanics reasons for the apparent 'constraint effects in fracture', followed by outlining a straightforward approach to overcoming this problem in both brittle (elastic) and ductile (elastic-plastic) fracture. It is concluded by discussing the major difference in constraint effect on fracture event in elastic and elastic-plastic materials.

  13. Astrophysical and cosmological constraints to neutrino properties

    NASA Technical Reports Server (NTRS)

    Kolb, Edward W.; Schramm, David N.; Turner, Michael S.

    1989-01-01

    The astrophysical and cosmological constraints on neutrino properties (masses, lifetimes, numbers of flavors, etc.) are reviewed. The freeze out of neutrinos in the early Universe are discussed and then the cosmological limits on masses for stable neutrinos are derived. The freeze out argument coupled with observational limits is then used to constrain decaying neutrinos as well. The limits to neutrino properties which follow from SN1987A are then reviewed. The constraint from the big bang nucleosynthesis on the number of neutrino flavors is also considered. Astrophysical constraints on neutrino-mixing as well as future observations of relevance to neutrino physics are briefly discussed.

  14. Private sector involvement in times of armed conflict: What are the constraints for trading medical equipment?

    PubMed

    Schmidt, Georg

    Today, healthcare facilities are highly dependent on the private sector to keep their medical equipment functioning. Moreover, private sector involvement becomes particularly important for the supply of spare parts and consumables. However, in times of armed conflict, the capacity of the corporate world appears to be seriously hindered. Subsequently, this study researches the influence of armed conflict on the private medical equipment sector. This study follows a qualitative approach by conducting 19 interviews with representatives of the corporate world in an active conflict zone. A semistructured interview guide, consisting of 10 questions, was used to examine the constraints of this sector. The results reveal that the lack of skilled personnel, complicated importation procedures, and a decrease in financial capacity are the major constraints faced by private companies dealing in medical equipment in conflict zones. Even when no official sanctions and embargoes for medical items exist, constraints for trading medical equipment are clearly recognizable. Countries at war would benefit from a centralized structure that deals with the importation procedures for medical items, to assist local companies in their purchasing procedures. A high degree of adaption is needed to continue operating, despite the emerging constraints of armed conflict. Future studies might research the constraints for manufacturers outside the conflict to export medical items to the country of war.

  15. Primary Art Resource Guide.

    ERIC Educational Resources Information Center

    Newton Unified School District 373, KS.

    GRADES OR AGES: Primary Grades. SUBJECT MATTER: Art. ORGANIZATION AND PHYSICAL APPEARANCE: The guide begins with a list of topics for art expression. The main body of the guide contains 15 color-coded sections on the following subjects: 1) mobiles and folded paper; 2) collage and photo montage; 3) square paper and mosaics; 4) wax paper and…

  16. Oregon Trail Teacher's Guide.

    ERIC Educational Resources Information Center

    National Park Service (Dept. of Interior), Washington, DC.

    The road to the U.S. West, known as the Oregon Trail, had its first real traffic in 1843 when a group of about 1000 people left Independence, Missouri and traveled west. This teacher's guide contains short descriptions of the main landmarks and stopping points that were significant along the northwest portion of the Oregon Trail. The guide is…

  17. Irrigation Systems. Instructor's Guide.

    ERIC Educational Resources Information Center

    Amarillo Coll., TX.

    This guide is intended for use by licensed irrigators who wish to teach others how to design and install residential and commercial irrigation systems. The materials included in the guide have been developed under the assumption that the instructors who use it have little or no formal training as teachers. The first section presents detailed…

  18. Livestock. Student Learning Guides.

    ERIC Educational Resources Information Center

    Ridge Vocational-Technical Center, Winter Haven, FL.

    These 25 learning guides are self-instructional packets for 25 tasks identified as essential for performance on an entry-level job in livestock production. Each guide is based on a terminal performance objective (task) and 1-4 enabling objectives. For each enabling objective, some or all of these materials may be presented: learning steps (outline…

  19. BONES, TEACHER'S GUIDE.

    ERIC Educational Resources Information Center

    Elementary Science Study, Newton, MA.

    THIS GUIDE WAS DEVELOPED FOR USE WITH THE ELEMENTARY SCIENCE STUDY UNIT ON "BONES.""BONES" HAS BEEN TAUGHT IN THE FOURTH GRADE AND REQUIRES FROM 10 TO 25 LESSONS, DEPENDING ON THE NUMBER OF ACTIVITIES USED. THE GUIDE DOES NOT PROVIDE DETAILED INSTRUCTION FOR CONDUCTING CLASSES, BUT RATHER SOME POSSIBLE ACTIVITIES, AND LEAVES…

  20. Curriculum Guide Construction Cluster.

    ERIC Educational Resources Information Center

    Kline, Ken

    As part of a model construction cluster curriculum development project, this guide was developed and implemented in the Beaverton (Oregon) School District. The curriculum guide contains 16 units covering the following topics: introduction to construction jobs; safety and first aid; blueprint readings; basic mathematics; site work; framing; roofing…

  1. Understanding Math - Teachers Guide.

    ERIC Educational Resources Information Center

    Wyks, Hollis W.; Austin, Robert J.

    The teacher's guide for the remedial text-workbook "Understanding Math" discusses instruction of the deaf student. An answer key for workbooks 1 and 2, a section with masters for transparencies to be used for games and activities and for teaching fractions, and two patterns for making geometric solids are included in the guide. For workbooks 1 and…

  2. Cluster Guide. Accounting Occupations.

    ERIC Educational Resources Information Center

    Beaverton School District 48, OR.

    Based on a recent task inventory of key occupations in the accounting cluster taken in the Portland, Oregon, area, this curriculum guide is intended to assist administrators and teachers in the design and implementation of high school accounting cluster programs. The guide is divided into four major sections: program organization and…

  3. Student Needs Assessment Guide.

    ERIC Educational Resources Information Center

    Lewis, Jean; And Others

    Designed as a component of a career exploratory program at Vale Middle School, Vale, Oregon, the Student Needs Assessment Guide provides middle school teachers with an instrument to be used in helping students assess themselves as individuals and to match this assessment with current and expected roles in the adult world. The guide consists of two…

  4. Business Management Course Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Vocational Education.

    This course guide is designed for teaching about the U.S. business system. Students are introduced to management functions and the background knowledge/skills necessary to be a successful manager. The guide contains 10 competency goals: (1) nature of U.S. business; (2) environment of business; (3) types of business ownership; (4) management…

  5. Graphic Communications. Curriculum Guide.

    ERIC Educational Resources Information Center

    North Dakota State Board for Vocational Education, Bismarck.

    This guide provides the basic foundation to develop a one-semester course based on the cluster concept, graphic communications. One of a set of six guides for an industrial arts curriculum at the junior high school level, it suggests exploratory experiences designed to (1) develop an awareness and understanding of the drafting and graphic arts…

  6. Katimavik Participant Information Guide.

    ERIC Educational Resources Information Center

    OPCAN, Montreal (Quebec).

    The guide provides prospective participants with an overview of Katimavik, a 9-month community volunteer service and learning program for 17- to 21-year-olds sponsored since 1977 by the Canadian Government. The guide describes the application process and computerized random selection procedures; work projects, which may range from building…

  7. Measurement Practice Guide

    ERIC Educational Resources Information Center

    College and Career Readiness and Success Center, 2014

    2014-01-01

    This discussion guide is part of a larger practice guide designed to help state education agencies (SEAs) define measurement goals, select college and career readiness measures and indicators designed to support those goals, and use the data gathered with those measures and indicators to make informed decisions about college and career readiness…

  8. Women's History Curriculum Guide.

    ERIC Educational Resources Information Center

    Ruthsdotter, Mary, Ed.; Eisenberg, Bonnie, Ed.

    This curriculum guide is designed to facilitate teachers' first efforts to introduce information about women in U.S. history. The guide promotes a multicultural awareness of women's history beginning with the Native Americans and proceeding to current issues of diversity. Activities are divided for grades 1-6 and 7-12 but may be adapted as…

  9. INDUSTRIAL RADIOGRAPHY INSTRUCTOR'S GUIDE.

    ERIC Educational Resources Information Center

    Bureau of Adult, Vocational, and Technical Education (DHEW/OE), Washington, DC. Div. of Vocational and Technical Education.

    THIS LABORATORY GUIDE WAS DEVELOPED FOR AN 80-HOUR COURSE IN INDUSTRIAL RADIOGRAPHY FOR HIGH SCHOOL GRADUATES TRAINING TO BECOME BEGINNING RADIOGRAPHERS. IT IS USED IN CONJUNCTION WITH TWO OTHER VOLUMES--(1) INDUSTRIAL RADIOGRAPHY INSTRUCTOR'S GUIDE, AND (2) INUDSTRIAL RADIOGRAPHY MANUAL. THE PROGRAM WAS DEVELOPED BY A COMMITTEE OF REPRESENTATIVES…

  10. Irrigation Systems. Student's Guide.

    ERIC Educational Resources Information Center

    Amarillo Coll., TX.

    This guide is intended for use by individuals preparing for a career in commercial and residential irrigation. The materials included are geared toward students who have had some experience in the irrigation business; they are intended to be presented in 10 six-hour sessions. The first two sections deal with using this guide and preparing for the…

  11. Career Education Instructional Guide.

    ERIC Educational Resources Information Center

    State Univ. of New York, Oswego. Coll. at Oswego. Dept. of Industrial Arts and Technology.

    The guide is designed primarily for industrial arts teachers at the middle school level who wish to integrate career education into their curricula. The lessons and activities attempt to establish a balance among career information, technical information, and hands-on experience. The guide contains six lesson plans which cover the topics: the…

  12. Guide to "Rhythmically Moving."

    ERIC Educational Resources Information Center

    Carlton, Elizabeth B.; Weikart, Phyllis S.

    This guide accompanies a series of recordings called "Rhythmically Moving." The series of nine recordings is a rare collection of international folk music designed to aid students as they learn to develop basic timing and musicianship. This guide helps the user of the series to receive maximum benefit from the first of the recordings (RM1). Using…

  13. User's Guide for SKETCH

    NASA Technical Reports Server (NTRS)

    Hedgley, David R., Jr.

    2000-01-01

    A user's guide for the computer program SKETCH is presented on this disk. SKETCH solves a popular problem in computer graphics-the removal of hidden lines from images of solid objects. Examples and illustrations are included in the guide. Also included is the SKETCH program, so a user can incorporate the information into a particular software system.

  14. Manufacturing Technology. Curriculum Guide.

    ERIC Educational Resources Information Center

    North Dakota State Board for Vocational Education, Bismarck.

    This guide provides the basic foundation to develop a one-semester course based on the cluster concept, manufacturing technology. One of a set of six guides for an industrial arts curriculum at the junior high school level, it suggests activities that allow students (1) to become familiar with and use some of the tools, materials, and processes…

  15. Marketing Education Curriculum Guide.

    ERIC Educational Resources Information Center

    Michigan State Univ., East Lansing. Coll. of Agriculture and Natural Resources Education Inst.

    This curriculum guide is intended to provide a common core of competencies from which to design an effective secondary marketing education program. Introductory materials include a definition of marketing education, objectives, outline of instructional content, and questions and answers regarding the curriculum guide. These practical materials are…

  16. BONES, TEACHER'S GUIDE.

    ERIC Educational Resources Information Center

    Elementary Science Study, Newton, MA.

    THIS GUIDE WAS DEVELOPED FOR USE WITH THE ELEMENTARY SCIENCE STUDY UNIT ON "BONES.""BONES" HAS BEEN TAUGHT IN THE FOURTH GRADE AND REQUIRES FROM 10 TO 25 LESSONS, DEPENDING ON THE NUMBER OF ACTIVITIES USED. THE GUIDE DOES NOT PROVIDE DETAILED INSTRUCTION FOR CONDUCTING CLASSES, BUT RATHER SOME POSSIBLE ACTIVITIES, AND LEAVES…

  17. User's guide to SILVAH

    Treesearch

    Peter D. Knopp; Susan L. Stout

    2014-01-01

    This user's guide for the SILVAH computer program, version 6.2, supersedes the 1992 user's guide (Gen. Tech. Rep. NE-162). Designed for stand-alone Windows-based personal computers, SILVAH recommends a silvicultural prescription for a forest stand based on a summary and analysis of field inventory data. The program also includes a simulator that can be used...

  18. GEOMETRY, TENTATIVE GUIDES.

    ERIC Educational Resources Information Center

    KLIER, KATHERINE M.

    PRESENTED IS A FUSED COURSE IN PLANE, SOLID, AND COORDINATE GEOMETRY. ELEMENTARY SET THEORY, LOGIC, AND THE PRINCIPLE OF SEPARATION PROVIDE UNIFYING THREADS THROUGHOUT THE TEXT. THE TWO CURRICULUM GUIDES HAVE BEEN PREPARED FOR USE WITH TWO DIFFERENT TEXTS. EITHER CURRICULUM GUIDE MAY BE USED DEPENDING UPON THE CHOICE OF THE TEACHER AND THE NEEDS…

  19. 2010 buyer's guide

    SciTech Connect

    2009-12-15

    This annual buyers' guide provides a resource for identifying the companies that provide the products and services required in the power generation industry. It is divided into 3 sections, namely products, services and companies. More than 1750 suppliers mostly in the USA are listed in over 400 product categories. The Buyer's Guide is also available online at www.power-eng.com.

  20. Livestock. Student Learning Guides.

    ERIC Educational Resources Information Center

    Ridge Vocational-Technical Center, Winter Haven, FL.

    These 25 learning guides are self-instructional packets for 25 tasks identified as essential for performance on an entry-level job in livestock production. Each guide is based on a terminal performance objective (task) and 1-4 enabling objectives. For each enabling objective, some or all of these materials may be presented: learning steps (outline…