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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. 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.

  4. Genetic constraints predict evolutionary divergence in Dalechampia blossoms

    PubMed Central

    Bolstad, Geir H.; Hansen, Thomas F.; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W. Scott

    2014-01-01

    If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance. PMID:25002700

  5. Genetic constraints predict evolutionary divergence in Dalechampia blossoms.

    PubMed

    Bolstad, Geir H; Hansen, Thomas F; Pélabon, Christophe; Falahati-Anbaran, Mohsen; Pérez-Barrales, Rocío; Armbruster, W Scott

    2014-08-19

    If genetic constraints are important, then rates and direction of evolution should be related to trait evolvability. Here we use recently developed measures of evolvability to test the genetic constraint hypothesis with quantitative genetic data on floral morphology from the Neotropical vine Dalechampia scandens (Euphorbiaceae). These measures were compared against rates of evolution and patterns of divergence among 24 populations in two species in the D. scandens species complex. We found clear evidence for genetic constraints, particularly among traits that were tightly phenotypically integrated. This relationship between evolvability and evolutionary divergence is puzzling, because the estimated evolvabilities seem too large to constitute real constraints. We suggest that this paradox can be explained by a combination of weak stabilizing selection around moving adaptive optima and small realized evolvabilities relative to the observed additive genetic variance. PMID:25002700

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

    MedlinePlus

    Making Sense of Your Genes a Guide to Genetic Counseling 1 A Guide to Genetic Counseling Contents What is genetic counseling? 1 Why might I ... methods contained in the material therein. Understanding Your Genes What is genetic counseling? The goal of genetic ...

  7. 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. PMID:20718267

  8. Genetic constraints on dishonesty and caste dimorphism in an ant.

    PubMed

    Holman, Luke; Linksvayer, Timothy A; d'Ettorre, Patrizia

    2013-02-01

    The ultimate causes of honest signaling remain a subject of debate, with questions remaining over the relative importance of costs and constraints. Signal costs may make dishonesty prohibitively expensive, while genetic constraints could make it impossible. We investigated honest signaling using full-sib analysis and parent-offspring regression in the ant Lasius niger, in which queens produce a cuticular hydrocarbon-based pheromone that signals fertility and inhibits worker reproduction and aggression. We found multiple lines of evidence that cuticular hydrocarbon production is genetically correlated with oogenesis and that the queen pheromone 3-methylhentriacontane and other 3-methylalkanes have strong genetic links with fertility relative to other cuticular hydrocarbons. These genetic correlations may maintain honesty in the face of directional selection on signaling and explain the putatively widespread use of cuticular hydrocarbons in fertility signaling across the social insects. We also found evidence for a positive genetic correlation for fertility between the castes; that is, the most fertile queens produced especially fertile workers. These results highlight that intercaste genetic correlations could constrain the evolution of queen-worker dimorphism, such that worker reproduction may sometimes reflect a nonadaptive "caste load" rather than positively selected cheating. PMID:23348771

  9. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:25716795

  11. 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

  12. 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. PMID:10350791

  13. Language Evolution: Constraints and Opportunities From Modern Genetics.

    PubMed

    Dediu, Dan; Christiansen, Morten H

    2016-04-01

    Our understanding of language, its origins and subsequent evolution (including language change), is shaped not only by data and theories from the language sciences, but also fundamentally by the biological sciences. Recent developments in genetics and evolutionary theory offer both very strong constraints on what scenarios of language evolution are possible and probable, but also offer exciting opportunities for understanding otherwise puzzling phenomena. Due to the intrinsic breathtaking rate of advancement in these fields, and the complexity, subtlety, and sometimes apparent non-intuitiveness of the phenomena discovered, some of these recent developments have either being completely missed by language scientists or misperceived and misrepresented. In this short paper, we offer an update on some of these findings and theoretical developments through a selection of illustrative examples and discussions that cast new light on current debates in the language sciences. The main message of our paper is that life is much more complex and nuanced than anybody could have predicted even a few decades ago, and that we need to be flexible in our theorizing instead of embracing a priori dogmas and trying to patch paradigms that are no longer satisfactory. PMID:26969626

  14. 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. PMID:24766696

  15. The hitchhiker's guide to Xenopus genetics.

    PubMed

    Abu-Daya, Anita; Khokha, Mustafa K; Zimmerman, Lyle B

    2012-03-01

    A decade after the human genome sequence, most vertebrate gene functions remain poorly understood, limiting benefits to human health from rapidly advancing genomic technologies. Systematic in vivo functional analysis is ideally suited to the experimentally accessible Xenopus embryo, which combines embryological accessibility with a broad range of transgenic, biochemical, and gain-of-function assays. The diploid X. tropicalis adds loss-of-function genetics and enhanced genomics to this repertoire. In the last decade, diverse phenotypes have been recovered from genetic screens, mutations have been cloned, and reverse genetics in the form of TILLING and targeted gene editing have been established. Simple haploid genetics and gynogenesis and the very large number of embryos produced streamline screening and mapping. Improved genomic resources and the revolution in high-throughput sequencing are transforming mutation cloning and reverse genetic approaches. The combination of loss-of-function mutant backgrounds with the diverse array of conventional Xenopus assays offers a uniquely flexible platform for analysis of gene function in vertebrate development. PMID:22344745

  16. Genetic variation, simplicity, and evolutionary constraints for function-valued traits.

    PubMed

    Kingsolver, Joel G; Heckman, Nancy; Zhang, Jonathan; Carter, Patrick A; Knies, Jennifer L; Stinchcombe, John R; Meyer, Karin

    2015-06-01

    Understanding the patterns of genetic variation and constraint for continuous reaction norms, growth trajectories, and other function-valued traits is challenging. We describe and illustrate a recent analytical method, simple basis analysis (SBA), that uses the genetic variance-covariance (G) matrix to identify "simple" directions of genetic variation and genetic constraints that have straightforward biological interpretations. We discuss the parallels between the eigenvectors (principal components) identified by principal components analysis (PCA) and the simple basis (SB) vectors identified by SBA. We apply these methods to estimated G matrices obtained from 10 studies of thermal performance curves and growth curves. Our results suggest that variation in overall size across all ages represented most of the genetic variance in growth curves. In contrast, variation in overall performance across all temperatures represented less than one-third of the genetic variance in thermal performance curves in all cases, and genetic trade-offs between performance at higher versus lower temperatures were often important. The analyses also identify potential genetic constraints on patterns of early and later growth in growth curves. We suggest that SBA can be a useful complement or alternative to PCA for identifying biologically interpretable directions of genetic variation and constraint in function-valued traits. PMID:25996868

  17. 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.

  18. Legal constraints on genetic data processing in European grids.

    PubMed

    Mouw, Evert; van't Noordende, Guido; van Kampen, Antoine H C; Louter, Baas; Santcroos, Mark; Olabarriaga, Silvia D

    2012-01-01

    European laws on privacy and data security are not explicit about the storage and processing of genetic data. Especially whole-genome data is identifying and contains a lot of personal information. Is processing of such data allowed in computing grids? To find out, we looked at legal precedents in related fields, current literature, and interviews with legal experts. We found that processing of genetic data is only allowed on distributed systems with specific security measures, both technical and organizational. Informed consent, although important, offers no substitute for such requirements. PMID:22941987

  19. Selective and Genetic Constraints on Pneumococcal Serotype Switching

    PubMed Central

    Croucher, Nicholas J.; Kagedan, Lisa; Thompson, Claudette M.; Parkhill, Julian; Bentley, Stephen D.; Finkelstein, Jonathan A.; Lipsitch, Marc; Hanage, William P.

    2015-01-01

    Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes), which can be classified into “serogroups” based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps) locus. Twenty such “serotype switching” events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001) enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β–lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern. PMID:25826208

  20. Constraints on decision making: implications from genetics, personality, and addiction.

    PubMed

    Baker, Travis E; Stockwell, Tim; Holroyd, Clay B

    2013-09-01

    An influential neurocomputational theory of the biological mechanisms of decision making, the "basal ganglia go/no-go model," holds that individual variability in decision making is determined by differences in the makeup of a striatal system for approach and avoidance learning. The model has been tested empirically with the probabilistic selection task (PST), which determines whether individuals learn better from positive or negative feedback. In accordance with the model, in the present study we examined whether an individual's ability to learn from positive and negative reinforcement can be predicted by genetic factors related to the midbrain dopamine system. We also asked whether psychiatric and personality factors related to substance dependence and dopamine affect PST performance. Although we found characteristics that predicted individual differences in approach versus avoidance learning, these observations were qualified by additional findings that appear inconsistent with the predictions of the go/no-go model. These results highlight a need for future research to validate the PST as a measure of basal ganglia reward learning. PMID:23658007

  1. 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

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

    PubMed

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

    2014-07-21

    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, respectively

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

    PubMed

    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 between organisms, a

  4. 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

  5. Seasonal time constraints reduce genetic variation in life-history traits along a latitudinal gradient.

    PubMed

    Sniegula, Szymon; Golab, Maria J; Drobniak, Szymon M; Johansson, Frank

    2016-01-01

    Time constraints cause strong selection on life-history traits, because populations need to complete their life cycles within a shorter time. We therefore expect lower genetic variation in these traits in high- than in low-latitude populations, since the former are more time-constrained. The aim was to estimate life-history traits and their genetic variation in an obligately univoltine damselfly along a latitudinal gradient of 2730 km. Populations were grown in the laboratory at temperatures and photoperiods simulating those at their place of origin. In a complementary experiment, individuals from the same families were grown in constant temperature and photoperiod that mimicked average conditions across the latitude. Development time and size was faster and smaller, respectively, and growth rate was higher at northern latitudes. Additive genetic variance was very low for life-history traits, and estimates for egg development time and larval growth rate showed significant decreases towards northern latitudes. The expression of genetic effects in life-history traits differed considerably when individuals were grown in constant rather than simulated and naturally variable conditions. Our results support strong selection by time constraints. They also highlight the importance of growing organisms in their native environment for correct estimates of genetic variance at their place of origin. Our results also suggest that the evolutionary potential of life-history traits is very low at northern compared to southern latitudes, but that changes in climate could alter this pattern. PMID:26333659

  6. 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

  7. Multi-atlas Based Segmentation Editing with Interaction-Guided Constraints

    PubMed Central

    Park, Sang Hyun; Gao, Yaozong; Shen, Dinggang

    2015-01-01

    We propose a novel multi-atlas based segmentation method to address the editing scenario, when given an incomplete segmentation along with a set of training label images. Unlike previous multi-atlas based methods, which depend solely on appearance features, we incorporate interaction-guided constraints to find appropriate training labels and derive their voting weights. Specifically, we divide user interactions, provided on erroneous parts, into multiple local interaction combinations, and then locally search for the training label patches well-matched with each interaction combination and also the previous segmentation. Then, we estimate the new segmentation through the label fusion of selected label patches that have their weights defined with respect to their respective distances to the interactions. Since the label patches are found to be from different combinations in our method, various shape changes can be considered even with limited training labels and few user interactions. Since our method does not need image information or expensive learning steps, it can be conveniently used for most editing problems. To demonstrate the positive performance, we apply our method to editing the segmentation of three challenging data sets: prostate CT, brainstem CT, and hippocampus MR. The results show that our method outperforms the existing editing methods in all three data sets. PMID:26942234

  8. 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

  9. Relaxed Genetic Constraint is Ancestral to the Evolution of Phenotypic Plasticity

    PubMed Central

    Leichty, Aaron R.; Pfennig, David W.; Jones, Corbin D.; Pfennig, Karin S.

    2012-01-01

    Phenotypic plasticity––the capacity of a single genotype to produce different phenotypes in response to varying environmental conditions––is widespread. Yet, whether, and how, plasticity impacts evolutionary diversification is unclear. According to a widely discussed hypothesis, plasticity promotes rapid evolution because genes expressed differentially across different environments (i.e., genes with “biased” expression) experience relaxed genetic constraint and thereby accumulate variation faster than do genes with unbiased expression. Indeed, empirical studies confirm that biased genes evolve faster than unbiased genes in the same genome. An alternative hypothesis holds, however, that the relaxed constraint and faster evolutionary rates of biased genes may be a precondition for, rather than a consequence of, plasticity’s evolution. Here, we evaluated these alternative hypotheses by characterizing evolutionary rates of biased and unbiased genes in two species of frogs that exhibit a striking form of phenotypic plasticity. We also characterized orthologs of these genes in four species of frogs that had diverged from the two plastic species before the plasticity evolved. We found that the faster evolutionary rates of biased genes predated the evolution of the plasticity. Furthermore, biased genes showed greater expression variance than did unbiased genes, suggesting that they may be more dispensable. Phenotypic plasticity may therefore evolve when dispensable genes are co-opted for novel function in environmentally induced phenotypes. Thus, relaxed genetic constraint may be a cause––not a consequence––of the evolution of phenotypic plasticity, and thereby contribute to the evolution of novel traits. PMID:22526866

  10. 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

  11. 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.

  12. 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

  13. 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. PMID:24740142

  14. Using Genetic Testing to Guide Therapeutic Decisions in Cardiomyopathy

    PubMed Central

    Lakdawala, Neal K

    2013-01-01

    Opinion statement Genetic analysis of human cardiomyopathy has rapidly transitioned from a strictly research endeavor to a diagnostic tool readily available to clinicians across the globe. In contemporary practice, genetic testing improves the efficiency of family evaluations and clarifies the etiology of ambiguous clinical presentations. The great promise of genetic diagnosis is to enable preventative therapies for individuals at high risk of future disease development, a strategy that is under active clinical investigation. However, in the present and future, careful interpretation of DNA sequence variation is critical, and can be ensured by referral to a specialized cardiovascular genetics clinic. PMID:23794152

  15. The Life Course Perspective: a Guide for Genetic Counselors.

    PubMed

    Hamilton, Rebekah J; Innella, Nancy A; Bounds, Dawn T

    2016-02-01

    This is the first article in a two part series about utilizing the life course perspective (LCP) in genetic counseling. LCP can be a useful tool for genetic counselors when counseling people with a known genetic mutation. Previous theories such as Protection Motivation Theory (PMT) and Common Sense Model of Self-Regulation (CSMSR) examine current reactions to a positive genetic test result. LCP extends beyond the current time to explore temporal and contextual elements of the experience. A review of research revealed, LCP has been used to study the perspective of caregivers of people with Alzheimer's disease, referral for a family history of breast cancer, Mexican American caregivers of older adult, social class and cancer incidence and cancer and the sense of mastery. Incorporating LCP into a study explaining the experiences of people living with a positive test result for a genetic mutation such as the BRCA mutation provides a comprehensive exploration of this experience. PMID:26306684

  16. 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…

  17. Genetic constraints and the adaptive evolution of rabies virus in nature.

    PubMed

    Holmes, Edward C; Woelk, Christopher H; Kassis, Raid; Bourhy, Hervé

    2002-01-20

    We used a molecular evolutionary approach to investigate the species adaptation of rabies virus in nature. A maximum likelihood analysis of selection pressures revealed that the nucleoprotein (N) and glycoprotein (G) genes of natural viral isolates were highly constrained, especially at nonsynonymous sites, in contrast to the higher rates of nonsynonymous evolution observed in viruses subject to laboratory passage. Positive selection was only found at a single amino acid site--position 183 in the ectodomain of the G gene. The low rate of nonsynonymous evolution in natural isolates of rabies virus may be due to constraints imposed by the need to replicate in multiple cell types within the host, which in turn facilitates cross-species transmission, or because viral proteins are not subject to immune selection. Using known dates in the epidemiologic history of European viral isolates, we estimated that overall rates of nucleotide substitution in rabies virus were similar to those observed in other RNA viruses. Assuming that the average rate of synonymous change does not vary among species, we estimated that the current genetic diversity in lyssavirus genotype 1 may have arisen only during the last 500 years. PMID:11878928

  18. 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

  19. 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. PMID:19092760

  20. 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,…

  1. 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…

  2. Use of genetic data to guide therapy in arterial disease.

    PubMed

    Ross, S; Nejat, S; Paré, G

    2015-06-01

    There is considerable interindividual variation in the response to antiplatelet and anticoagulant therapies. It has been proposed that this variability in drug response may be attributable to genetic variants. Thus, pharmacogenetics may help to accurately predict response to cardiovascular disease (CVD) therapies in order to maximize drug efficacy, minimize drug toxicity, and to tailor personalized care for these patients. Although the clinical utility of pharmacogenetics is promising, its adoption in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies. Thus, this review focuses on the genetic determinants of commonly used platelet antagonists and anticoagulants including aspirin, clopidogrel, dabigatran, and warfarin. We also explore the clinical translation of pharmacogenetics in the management of patients with CVD. PMID:26149037

  3. Spatiotemporal coordination behaviors in futsal (indoor football) are guided by informational game constraints.

    PubMed

    Travassos, B; Araújo, D; Duarte, R; McGarry, T

    2012-08-01

    This report investigated the behavioral dynamics of teams in futsal game practice when the goalkeeper of the attacking team is substituted for an extra outfield player. To this end, the lateral and longitudinal displacements of the ball and both teams, as well as their kinematics expressed in angles and radial distances from the goal center, were obtained and subjected to relative phase analysis. The results demonstrated (a) stronger phase relations with the ball for the defending team than the attacking team for both coordinate systems, (b) phase relations between each team and ball, and, to a lesser extent, between teams themselves, produced greater stabilities in the lateral (side-to-side) direction than the longitudinal (forward-backward) direction, and (c) phase attractions were most pronounced for the defending team and ball when using angles as a measure of association, indicating ball position and goal location as key informational constraints for futsal game behavior. These findings advance understanding of self-organizing sports game dynamics with implications for sports practice. PMID:22672740

  4. 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. PMID:26895461

  5. 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

  6. 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.

  7. 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.

  8. Large-Scale Single-Guide RNA Library Construction and Use for Genetic Screens

    PubMed Central

    Wang, Tim; Lander, Eric S.; Sabatini, David M.

    2016-01-01

    The ability to systematically disrupt genes serves as a powerful tool for understanding their function. The programmable Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system enables efficient targeting of large numbers of genes through the use of single-guide RNA (sgRNA) libraries. In cultured mammalian cells, collections of knockout mutants can be readily generated via transduction of Cas9/sgRNA lentiviral pools, screened for a phenotype of interest, and tracked using high-throughput DNA sequencing. This technique represents the first general method for undertaking systematic loss-of-function genetic screens in mammalian cells. In this chapter, we outline the steps for conducting CRISPR-based screens from the initial library design to final data analysis and provide guidelines for developing an appropriate screening strategy. PMID:26933254

  9. 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.

  10. Mechanism-guided library design and dual genetic selection of synthetic OFF riboswitches.

    PubMed

    Muranaka, Norihito; Abe, Koichi; Yokobayashi, Yohei

    2009-09-21

    After the recent discovery of bacterial riboswitches, synthetic riboswitches have been engineered by using natural and artificial RNA aptamers. In contrast to natural riboswitches, the majority of synthetic riboswitches in bacteria reported to date are ON switches that activate gene expression in response to the aptamer ligand. In this study, we adopted a mechanism-guided approach to design libraries predisposed to contain OFF riboswitches that respond to thiamine pyrophosphate (TPP). The first library design exploited a pseudo-Shine-Dalgarno (SD) sequence located near the 3'-end of the TPP aptamer, which would be less accessible to the ribosome when the aptamer is bound to TPP. In the second library, an SD sequence was strategically placed in the aptamer's P1 stem, which is stabilized upon ligand binding. OFF riboswitches were obtained by dual genetic selection of these libraries. The results underscore the importance of effective library design to achieve desired riboswitch functions. PMID:19658147

  11. Genetic Conditions: A Resource Book and Instructional Guide to Human Heredity and Birth Defects for Kindergarten Through Adult Education.

    ERIC Educational Resources Information Center

    California State Dept. of Education, Sacramento.

    Designed for administrators, teachers, school nurses, and others involved in health education for kindergarten through adult education, the resource guide provides curriculum ideas for instruction in genetic conditions, heredity, and birth defects. Student learning objectives, content information, learning activities, and evaluation methods are…

  12. 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. PMID:26956564

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

    PubMed Central

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

    2015-01-01

    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. PMID

  14. 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

    2015-04-01

    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. PMID

  15. 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

    ... Period. SUMMARY: On April 20, 2010 (75 FR 20645), the U. S. Nuclear Regulatory Commission (NRC) published... ADAMS Accession Number ML092600090. SUPPLEMENTARY INFORMATION: On April 20, 2010 (75 FR 20645), the NRC... Environment for Licensees Other Than Power Reactors,'' Proposed Revision 1 of Regulatory Guide 4.20;...

  16. 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

  17. DIAGNOSIS-GUIDED METHOD FOR IDENTIFYING MULTI-MODALITY NEUROIMAGING BIOMARKERS ASSOCIATED WITH GENETIC RISK FACTORS IN ALZHEIMER'S DISEASE.

    PubMed

    Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Zhang, Daoqiang; Shen, Li

    2016-01-01

    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods. PMID:26776178

  18. Diagnosis-Guided Method For Identifying Multi-Modality Neuroimaging Biomarkers Associated With Genetic Risk Factors In Alzheimer's Disease

    PubMed Central

    Hao, Xiaoke; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L.; Saykin, Andrew J.; Zhang, Daoqiang; Shen, Li

    2015-01-01

    Many recent imaging genetic studies focus on detecting the associations between genetic markers such as single nucleotide polymorphisms (SNPs) and quantitative traits (QTs). Although there exist a large number of generalized multivariate regression analysis methods, few of them have used diagnosis information in subjects to enhance the analysis performance. In addition, few of models have investigated the identification of multi-modality phenotypic patterns associated with interesting genotype groups in traditional methods. To reveal disease-relevant imaging genetic associations, we propose a novel diagnosis-guided multi-modality (DGMM) framework to discover multi-modality imaging QTs that are associated with both Alzheimer's disease (AD) and its top genetic risk factor (i.e., APOE SNP rs429358). The strength of our proposed method is that it explicitly models the priori diagnosis information among subjects in the objective function for selecting the disease-relevant and robust multi-modality QTs associated with the SNP. We evaluate our method on two modalities of imaging phenotypes, i.e., those extracted from structural magnetic resonance imaging (MRI) data and fluorodeoxyglucose positron emission tomography (FDG-PET) data in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The experimental results demonstrate that our proposed method not only achieves better performances under the metrics of root mean squared error and correlation coefficient but also can identify common informative regions of interests (ROIs) across multiple modalities to guide the disease-induced biological interpretation, compared with other reference methods. PMID:26776178

  19. 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. PMID:26878130

  20. 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. PMID:14592923

  1. P13.21ORGANS AT RISK IN THE BRAIN AND THEIR DOSE-CONSTRAINTS IN THE ADULTS AND IN THE CHILDREN: A RADIATION ONCOLOGIST'S GUIDE FOR DELINEATION

    PubMed Central

    Scoccianti, S.; Detti, B.; Greto, D.; Gadda, D.; Furfaro, I.F.; Di Brina, L.; Meacci, F.; Cassani, S.; Giacomelli, I.; Livi, L.

    2014-01-01

    The aim of this study is to provide a stepwise contouring guide to delineate the organs at risk in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Acute and late toxicity with risk of visual and hearing deficits, hormonal impairment and neurocognitive alterations, is a critical point in radiation treatment of patients affected by brain tumors. Moreover, accurate delineation of organ at risks is essential for the inverse-planning process of intensity modulated radiation treatment (IMRT). However, anatomic cerebral normal structures are not always easily recognizable either on simulation CT scan and on coregistered MRI scan used for radiotherapy planning. We have developed a detailed anatomy atlas on Computed tomography (CT) imaging and magnetic resonance (MR) imaging of brain. The following regions of interest were defined: optic chiasm, cochlea, pituitary gland, temporal lobe and hippocampus. Some main notions of anatomy of the organs at risk are provided together with some landmarks easily to be found on the imaging scans. Detailed contouring recommendations are provided in order to significantly improve the contour accuracy and concordance. This report also provides for all the above-mentioned organs at risk a systematic review for the recommended dose constraints both for adult and pediatric patients. This guide is a useful tool for improving daily practice and decreasing the differences in organs at risk delineation between radiation oncologists.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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. PMID:23232833

  7. Location constraint based 2D-3D registration of fluoroscopic images and CT volumes for image-guided EP procedures

    NASA Astrophysics Data System (ADS)

    Liao, Rui; Xu, Ning; Sun, Yiyong

    2008-03-01

    Presentation of detailed anatomical structures via 3D Computed Tomographic (CT) volumes helps visualization and navigation in electrophysiology procedures (EP). Registration of the CT volume with the online fluoroscopy however is a challenging task for EP applications due to the lack of discernable features in fluoroscopic images. In this paper, we propose to use the coronary sinus (CS) catheter in bi-plane fluoroscopic images and the coronary sinus in the CT volume as a location constraint to accomplish 2D-3D registration. Two automatic registration algorithms are proposed in this study, and their performances are investigated on both simulated and real data. It is shown that compared to registration using mono-plane fluoroscopy, registration using bi-plane images results in substantially higher accuracy in 3D and enhanced robustness. In addition, compared to registering the projection of CS to the 2D CS catheter, it is more desirable to reconstruct a 3D CS catheter from the bi-plane fluoroscopy and then perform a 3D-3D registration between the CS and the reconstructed CS catheter. Quantitative validation based on simulation and visual inspection on real data demonstrates the feasibility of the proposed workflow in EP procedures.

  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. PMID:16614427

  9. Using Genetic Prediction from Known Complex Disease Loci to Guide the Design of Next-Generation Sequencing Experiments

    PubMed Central

    Jostins, Luke; Levine, Adam P.; Barrett, Jeffrey C.

    2013-01-01

    A central focus of complex disease genetics after genome-wide association studies (GWAS) is to identify low frequency and rare risk variants, which may account for an important fraction of disease heritability unexplained by GWAS. A profusion of studies using next-generation sequencing are seeking such risk alleles. We describe how already-known complex trait loci (largely from GWAS) can be used to guide the design of these new studies by selecting cases, controls, or families who are most likely to harbor undiscovered risk alleles. We show that genetic risk prediction can select unrelated cases from large cohorts who are enriched for unknown risk factors, or multiply-affected families that are more likely to harbor high-penetrance risk alleles. We derive the frequency of an undiscovered risk allele in selected cases and controls, and show how this relates to the variance explained by the risk score, the disease prevalence and the population frequency of the risk allele. We also describe a new method for informing the design of sequencing studies using genetic risk prediction in large partially-genotyped families using an extension of the Inside-Outside algorithm for inference on trees. We explore several study design scenarios using both simulated and real data, and show that in many cases genetic risk prediction can provide significant increases in power to detect low-frequency and rare risk alleles. The same approach can also be used to aid discovery of non-genetic risk factors, suggesting possible future utility of genetic risk prediction in conventional epidemiology. Software implementing the methods in this paper is available in the R package Mangrove. PMID:24204614

  10. Using genetic prediction from known complex disease Loci to guide the design of next-generation sequencing experiments.

    PubMed

    Jostins, Luke; Levine, Adam P; Barrett, Jeffrey C

    2013-01-01

    A central focus of complex disease genetics after genome-wide association studies (GWAS) is to identify low frequency and rare risk variants, which may account for an important fraction of disease heritability unexplained by GWAS. A profusion of studies using next-generation sequencing are seeking such risk alleles. We describe how already-known complex trait loci (largely from GWAS) can be used to guide the design of these new studies by selecting cases, controls, or families who are most likely to harbor undiscovered risk alleles. We show that genetic risk prediction can select unrelated cases from large cohorts who are enriched for unknown risk factors, or multiply-affected families that are more likely to harbor high-penetrance risk alleles. We derive the frequency of an undiscovered risk allele in selected cases and controls, and show how this relates to the variance explained by the risk score, the disease prevalence and the population frequency of the risk allele. We also describe a new method for informing the design of sequencing studies using genetic risk prediction in large partially-genotyped families using an extension of the Inside-Outside algorithm for inference on trees. We explore several study design scenarios using both simulated and real data, and show that in many cases genetic risk prediction can provide significant increases in power to detect low-frequency and rare risk alleles. The same approach can also be used to aid discovery of non-genetic risk factors, suggesting possible future utility of genetic risk prediction in conventional epidemiology. Software implementing the methods in this paper is available in the R package Mangrove. PMID:24204614

  11. Genetics

    MedlinePlus

    Homozygous; 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 ...

  12. 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 ...

  13. 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

  14. Alternative mutational pathways, outside the VPg, of rice yellow mottle virus to overcome eIF(iso)4G-mediated rice resistance under strong genetic constraints.

    PubMed

    Poulicard, Nils; Pinel-Galzi, Agnès; Fargette, Denis; Hébrard, Eugénie

    2014-01-01

    The adaptation of rice yellow mottle virus (RYMV) to rymv1-mediated resistance has been reported to involve mutations in the viral genome-linked protein (VPg). In this study, we analysed several cases of rymv1-2 resistance breakdown by an isolate with low adaptability. Surprisingly, in these rarely occurring resistance-breaking (RB) genotypes, mutations were detected outside the VPg, in the ORF2a/ORF2b overlapping region. The causal role of three mutations associated with rymv1-2 resistance breakdown was validated via directed mutagenesis of an infectious clone. In resistant plants, these mutations increased viral accumulation as efficiently as suboptimal RB mutations in the VPg. Interestingly, these mutations are located in a highly conserved, but unfolded, domain. Altogether, our results indicate that under strong genetic constraints, a priori unfit genotypes can follow alternative mutational pathways, i.e. outside the VPg, to overcome rymv1-2 resistance. PMID:24141250

  15. 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.

  16. Simulation of Finnish population history, guided by empirical genetic data, to assess power of rare-variant tests in Finland.

    PubMed

    Wang, Sophie R; Agarwala, Vineeta; Flannick, Jason; Chiang, Charleston W K; Altshuler, David; Hirschhorn, Joel N

    2014-05-01

    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

  17. In search of more complex genetic codes--can linguistics be a guide?

    PubMed

    Doerfler, W

    1982-12-01

    Striking similarities have been pointed out between the structures of the human language and the genetic code. The primary genetic code utilizes the principle of linear representation much like e.g. the Indo-European languages do. There are numerous indications that more complex secondary and tertiary structural elements in DNA direct highly specific interactions with proteins. Thus, more complex genetic codes might exist which might be superimposed on DNA sequences coding for polypeptides or might be extended to "non-coding" DNA sequences. Structural features of highly complex languages, like Chinese or Egyptian hieroglyphics using conceptual expression patterns have been compared to the more complex ways of encoding. It is proposed that the application of linguistic principles may be helpful in the computer analyses of known DNA sequences. There is considerable evidence for the innate specification at least for the basic structural elements of human languages. This innate specification may be the cause for language university. Based on the striking structural similarities between language and genetic code, the question is raised to what extent and in what way DNA sequences might be related to the innate specification of human languages. PMID:7167071

  18. Hippocampal transcriptome-guided genetic analysis of correlated episodic memory phenotypes in Alzheimer's disease

    PubMed Central

    Yan, Jingwen; Kim, Sungeun; Nho, Kwangsik; Chen, Rui; Risacher, Shannon L.; Moore, Jason H.; Saykin, Andrew J.; Shen, Li

    2015-01-01

    As the most common type of dementia, Alzheimer's disease (AD) is a neurodegenerative disorder initially manifested by impaired memory performances. While the diagnosis information indicates a dichotomous status of a patient, memory scores have the potential to capture the continuous nature of the disease progression and may provide more insights into the underlying mechanism. In this work, we performed a targeted genetic study of memory scores on an AD cohort to identify the associations between a set of genes highly expressed in the hippocampal region and seven cognitive scores related to episodic memory. Both main effects and interaction effects of the targeted genetic markers on these correlated memory scores were examined. In addition to well-known AD genetic markers APOE and TOMM40, our analysis identified a new risk gene NAV2 through the gene-level main effect analysis. NAV2 was found to be significantly and consistently associated with all seven episodic memory scores. Genetic interaction analysis also yielded a few promising hits warranting further investigation, especially for the RAVLT list B Score. PMID:25859259

  19. 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

  20. 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

  1. Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 signaling pathway.

    PubMed

    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

    2013-05-01

    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. Genetically distinct pathways guide effector export through the type VI secretion system

    PubMed Central

    Whitney, John C.; Beck, Christina M.; Goo, Young Ah; Russell, Alistair B.; Harding, Brittany; De Leon, Justin A.; Cunningham, David A.; Tran, Bao Q.; Low, David A.; Goodlett, David R.; Hayes, Christopher S.; Mougous, Joseph D.

    2014-01-01

    Summary Bacterial secretion systems often employ molecular chaperones to recognize and facilitate export of their substrates. Recent work demonstrated that a secreted component of the type VI secretion system (T6SS), hemolysin co-regulated protein (Hcp), binds directly to effectors, enhancing their stability in the bacterial cytoplasm. Herein, we describe a quantitative cellular proteomics screen for T6S substrates that exploits this chaperone-like quality of Hcp. Application of this approach to the Hcp secretion island I-encoded T6SS (H1-T6SS) of Pseudomonas aeruginosa led to the identification of a novel effector protein, termed Tse4 (type VI secretion exported 4), subsequently shown to act as a potent intra-specific H1-T6SS-delivered antibacterial toxin. Interestingly, our screen failed to identify two predicted H1-T6SS effectors, Tse5 and Tse6, which differ from Hcp-stabilized substrates by the presence of toxin-associated PAAR-repeat motifs and genetic linkage to members of the valine-glycine repeat protein G (vgrG) genes. Genetic studies further distinguished these two groups of effectors: Hcp-stabilized effectors were found to display redundancy in interbacterial competition with respect to the requirement for the two H1-T6SS-exported VgrG proteins, whereas Tse5 and Tse6 delivery strictly required a cognate VgrG. Together, we propose that interaction with either VgrG or Hcp defines distinct pathways for T6S effector export. PMID:24589350

  3. Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

    PubMed Central

    Li, Zhihua; Lee, Insuk; Moradi, Emily; Hung, Nai-Jung; Johnson, Arlen W.; Marcotte, Edward M.

    2009-01-01

    Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics—an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies—to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes—most with human orthologs—to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process. PMID:19806183

  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. PMID:26842621

  5. 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.

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

    PubMed

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

    2015-01-01

    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. PMID:25813537

  7. 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

  8. GADEM: a genetic algorithm guided formation of spaced dyads coupled with an EM algorithm for motif discovery.

    PubMed

    Li, Leping

    2009-02-01

    Genome-wide analyses of protein binding sites generate large amounts of data; a ChIP dataset might contain 10,000 sites. Unbiased motif discovery in such datasets is not generally feasible using current methods that employ probabilistic models. We propose an efficient method, GADEM, which combines spaced dyads and an expectation-maximization (EM) algorithm. Candidate words (four to six nucleotides) for constructing spaced dyads are prioritized by their degree of overrepresentation in the input sequence data. Spaced dyads are converted into starting position weight matrices (PWMs). GADEM then employs a genetic algorithm (GA), with an embedded EM algorithm to improve starting PWMs, to guide the evolution of a population of spaced dyads toward one whose entropy scores are more statistically significant. Spaced dyads whose entropy scores reach a pre-specified significance threshold are declared motifs. GADEM performed comparably with MEME on 500 sets of simulated "ChIP" sequences with embedded known P53 binding sites. The major advantage of GADEM is its computational efficiency on large ChIP datasets compared to competitors. We applied GADEM to six genome-wide ChIP datasets. Approximately, 15 to 30 motifs of various lengths were identified in each dataset. Remarkably, without any prior motif information, the expected known motif (e.g., P53 in P53 data) was identified every time. GADEM discovered motifs of various lengths (6-40 bp) and characteristics in these datasets containing from 0.5 to >13 million nucleotides with run times of 5 to 96 h. GADEM can be viewed as an extension of the well-known MEME algorithm and is an efficient tool for de novo motif discovery in large-scale genome-wide data. The GADEM software is available at (www.niehs.nih.gov/research/resources/software/GADEM/). PMID:19193149

  9. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  11. 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

  12. A Microsatellite Guided Insight into the Genetic Status of Adi, an Isolated Hunting-Gathering Tribe of Northeast India

    PubMed Central

    Krithika, S.; Maji, Suvendu; Vasulu, T. S.

    2008-01-01

    Tibeto-Burman populations of India provide an insight into the peopling of India and aid in understanding their genetic relationship with populations of East, South and Southeast Asia. The study investigates the genetic status of one such Tibeto-Burman group, Adi of Arunachal Pradesh based on 15 autosomal microsatellite markers. Further the study examines, based on 9 common microsatellite loci, the genetic relationship of Adi with 16 other Tibeto-Burman speakers of India and 28 neighboring populations of East and Southeast Asia. Overall, the results support the recent formation of the Adi sub-tribes from a putative ancestral group and reveal that geographic contiguity is a major influencing factor of the genetic affinity among the Tibeto-Burman populations of India. PMID:18596928

  13. Plant Germplasm Centers and Microbial Culture Collections: A User’s Guide to Key Genetic Resources for Plant Pathology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This User's Guide to microbial culture collections and collections of germplasm of higher plants contains a variety of instructional material. It specifies to potential users amongst the plant science community, but especially plant pathologists, how to locate collections on line or via corresponde...

  14. 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.

  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 ). PMID:25426642

  16. 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. PMID:17225228

  17. Method for optimal sensor deployment on 3D terrains utilizing a steady state genetic algorithm with a guided walk mutation operator based on the wavelet transform.

    PubMed

    Unaldi, Numan; Temel, Samil; Asari, Vijayan K

    2012-01-01

    One of the most critical issues of Wireless Sensor Networks (WSNs) is the deployment of a limited number of sensors in order to achieve maximum coverage on a terrain. The optimal sensor deployment which enables one to minimize the consumed energy, communication time and manpower for the maintenance of the network has attracted interest with the increased number of studies conducted on the subject in the last decade. Most of the studies in the literature today are proposed for two dimensional (2D) surfaces; however, real world sensor deployments often arise on three dimensional (3D) environments. In this paper, a guided wavelet transform (WT) based deployment strategy (WTDS) for 3D terrains, in which the sensor movements are carried out within the mutation phase of the genetic algorithms (GAs) is proposed. The proposed algorithm aims to maximize the Quality of Coverage (QoC) of a WSN via deploying a limited number of sensors on a 3D surface by utilizing a probabilistic sensing model and the Bresenham's line of sight (LOS) algorithm. In addition, the method followed in this paper is novel to the literature and the performance of the proposed algorithm is compared with the Delaunay Triangulation (DT) method as well as a standard genetic algorithm based method and the results reveal that the proposed method is a more powerful and more successful method for sensor deployment on 3D terrains. PMID:22666078

  18. 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. PMID:25809972

  19. Method for Optimal Sensor Deployment on 3D Terrains Utilizing a Steady State Genetic Algorithm with a Guided Walk Mutation Operator Based on the Wavelet Transform

    PubMed Central

    Unaldi, Numan; Temel, Samil; Asari, Vijayan K.

    2012-01-01

    One of the most critical issues of Wireless Sensor Networks (WSNs) is the deployment of a limited number of sensors in order to achieve maximum coverage on a terrain. The optimal sensor deployment which enables one to minimize the consumed energy, communication time and manpower for the maintenance of the network has attracted interest with the increased number of studies conducted on the subject in the last decade. Most of the studies in the literature today are proposed for two dimensional (2D) surfaces; however, real world sensor deployments often arise on three dimensional (3D) environments. In this paper, a guided wavelet transform (WT) based deployment strategy (WTDS) for 3D terrains, in which the sensor movements are carried out within the mutation phase of the genetic algorithms (GAs) is proposed. The proposed algorithm aims to maximize the Quality of Coverage (QoC) of a WSN via deploying a limited number of sensors on a 3D surface by utilizing a probabilistic sensing model and the Bresenham's line of sight (LOS) algorithm. In addition, the method followed in this paper is novel to the literature and the performance of the proposed algorithm is compared with the Delaunay Triangulation (DT) method as well as a standard genetic algorithm based method and the results reveal that the proposed method is a more powerful and more successful method for sensor deployment on 3D terrains. PMID:22666078

  20. Genetics Home Reference: adermatoglyphia

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions adermatoglyphia adermatoglyphia Enable Javascript to ...

  1. 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. PMID:24114976

  2. 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.

  3. The population genetics of sporophytic self-incompatibility in Senecio squalidus L. (Asteraceae): avoidance of mating constraints imposed by low S-allele number.

    PubMed Central

    Brennan, Adrian C; Harris, Stephen A; Hiscock, Simon J

    2003-01-01

    Senecio squalidus L. (Asteraceae) has been the subject of several ecological and population genetic studies due to its well-documented history of introduction, establishment and spread throughout Britain in the past 300 years. Our recent studies have focused on identifying and quantifying factors associated with the sporophytic self-incompatibility (SSI) system of S. squalidus that may have contributed to its success as a colonist. These findings are of general biological interest because they provide important insights into the short-term evolutionary dynamics of a plant mating system. The number of S-alleles in populations and their dominance interactions were investigated in eight wild British populations using cross-diallel studies. The numbers of S-alleles in British S. squalidus populations are typically low (average of 5.3 S-alleles) and the entire British population is estimated to possess no more than 7-11 S-alleles. Such low numbers of S-alleles are most probably a consequence of population bottlenecks associated with introduction and colonization. Potential evolutionary impacts on SSI caused by a paucity of S-alleles, such as restricted mate availability, are discussed, and we suggest that increased dominance interactions between S-alleles may be an important short-term means of increasing mate availability when S-allele numbers are low. PMID:12831471

  4. Genetics Home Reference: adiposis dolorosa

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions adiposis dolorosa adiposis dolorosa Enable ...

  5. Genetics Home Reference: Canavan disease

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Canavan disease Canavan disease Enable ...

  6. Genetics Home Reference: Carney complex

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Carney complex Carney complex Enable ...

  7. Genetics Home Reference: cardiofaciocutaneous syndrome

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions cardiofaciocutaneous syndrome cardiofaciocutaneous syndrome Enable ...

  8. Genetics Home Reference: Caffey disease

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Caffey disease Caffey disease Enable ...

  9. 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

  10. 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.

  11. ECOLOGICAL AND EVOLUTIONARY CONSTRAINTS TO HERBIVORE RESISTANCE IN A NATIVE PLANT-MULTIPLE HERBIVORE COMMUNITY

    EPA Science Inventory

    This research project will reveal that novel constraints on resistance emerge with a consideration of more than one herbivore species. These constraints include genetic correlations in resistance to different herbivores, ecological interactions among the herbivores, non-addit...

  12. AGU Legislative Guide available

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    A guide to help AGU members communicate with legislators and government agency officials is available free of charge from AGU headquarters. The guide is based on the premise that input from the scientific community assists government to make decisions based on the latest factual information available.AGU's Guide to Legislative Information and Contacts was developed by AGU's Committee on Public Affairs and is based largely on a publication of the American Institute of Biological Sciences. The guide briefly outlines the key steps in the legislative process and lists sources of information on legislation. The booklet also provides guidelines for corresponding with legislators a n d for providing scientific testimony to Congress. It also delineates some o f the constraints under which AGU must operate when undertaking legislative activities.

  13. Constraint Based Modeling Going Multicellular

    PubMed Central

    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. PMID:26904548

  14. Highly irregular quantum constraints

    NASA Astrophysics Data System (ADS)

    Klauder, John R.; Little, J. Scott

    2006-05-01

    Motivated by a recent paper of Louko and Molgado, we consider a simple system with a single classical constraint R(q) = 0. If ql denotes a generic solution to R(q) = 0, our examples include cases where R'(ql) ≠ 0 (regular constraint) and R'(ql) = 0 (irregular constraint) of varying order as well as the case where R(q) = 0 for an interval, such as a <= q <= b. Quantization of irregular constraints is normally not considered; however, using the projection operator formalism we provide a satisfactory quantization which reduces to the constrained classical system when planck → 0. It is noteworthy that irregular constraints change the observable aspects of a theory as compared to strictly regular constraints.

  15. 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…

  16. 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…

  17. 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.

  18. 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.

  19. Constraints in Quantum Geometrodynamics

    NASA Astrophysics Data System (ADS)

    Gentle, Adrian P.; George, Nathan D.; Miller, Warner A.; Kheyfets, Arkady

    We compare different treatments of the constraints in canonical quantum gravity. The standard approach on the superspace of 3-geometries treats the constraints as the sole carriers of the dynamic content of the theory, thus rendering the traditional dynamical equations obsolete. Quantization of the constraints in both the Dirac and ADM square root Hamiltonian approaches leads to the well known problems of time evolution. These problems of time are of both an interpretational and technical nature. In contrast, the geometrodynamic quantization procedure on the superspace of the true dynamical variables separates the issues of quantization from the enforcement of the constraints. The resulting theory takes into account states that are off-shell with respect to the constraints, and thus avoids the problems of time. We develop, for the first time, the geometrodynamic quantization formalism in a general setting and show that it retains all essential features previously illustrated in the context of homogeneous cosmologies.

  20. 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…

  1. Accounting 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 accounting. 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…

  2. 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…

  3. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions adenosine monophosphate deaminase deficiency adenosine ...

  4. Genetics Home Reference: Camurati-Engelmann disease

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Camurati-Engelmann disease Camurati-Engelmann ...

  5. Genetics Home Reference: Cantú syndrome

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Cantú syndrome Cantú syndrome Enable ...

  6. Genetics Home Reference: Buschke-Ollendorff syndrome

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions Buschke-Ollendorff syndrome Buschke-Ollendorff ...

  7. 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.

  8. Discovery and Structure-Guided Optimization of Diarylmethanesulfonamide Disrupters of Glucokinase-Glucokinase Regulatory Protein (GK-GKRP) Binding: Strategic Use of a N → S (nN → σ*S-X) Interaction for Conformational Constraint.

    PubMed

    Pennington, Lewis D; Bartberger, Michael D; Croghan, Michael D; Andrews, Kristin L; Ashton, Kate S; Bourbeau, Matthew P; Chen, Jie; Chmait, Samer; Cupples, Rod; Fotsch, Christopher; Helmering, Joan; Hong, Fang-Tsao; Hungate, Randall W; Jordan, Steven R; Kong, Ke; Liu, Longbin; Michelsen, Klaus; Moyer, Carolyn; Nishimura, Nobuko; Norman, Mark H; Reichelt, Andreas; Siegmund, Aaron C; Sivits, Glenn; Tadesse, Seifu; Tegley, Christopher M; Van, Gwyneth; Yang, Kevin C; Yao, Guomin; Zhang, Jiandong; Lloyd, David J; Hale, Clarence; St Jean, David J

    2015-12-24

    The HTS-based discovery and structure-guided optimization of a novel series of GKRP-selective GK-GKRP disrupters are revealed. Diarylmethanesulfonamide hit 6 (hGK-hGKRP IC50 = 1.2 μM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 μM). A stabilizing interaction between a nitrogen atom lone pair and an aromatic sulfur system (nN → σ*S-X) in 32 was exploited to conformationally constrain a biaryl linkage and allow contact with key residues in GKRP. Lead compound 32 was shown to induce GK translocation from the nucleus to the cytoplasm in rats (IHC score = 0; 10 mg/kg po, 6 h) and blood glucose reduction in mice (POC = -45%; 100 mg/kg po, 3 h). X-ray analyses of 32 and several precursors bound to GKRP were also obtained. This novel disrupter of GK-GKRP binding enables further exploration of GKRP as a potential therapeutic target for type II diabetes and highlights the value of exploiting unconventional nonbonded interactions in drug design. PMID:26551034

  9. 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

  10. Spectrum and Classification of ATP7B Variants in a Large Cohort of Chinese Patients with Wilson's Disease Guides Genetic Diagnosis

    PubMed Central

    Dong, Yi; Ni, Wang; Chen, Wan-Jin; Wan, Bo; Zhao, Gui-Xian; Shi, Zhu-Qing; Zhang, Yue; Wang, Ning; Yu, Long; Xu, Jian-Feng; Wu, Zhi-Ying

    2016-01-01

    Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by ATP7B pathogenic mutations. The symptoms of WD can be effectively prevented if the affected individuals are identified and intervened early. However, clinical utility of this molecular analysis is challenging due to hundreds of variants with various clinical effects in the gene. Here, we aim to describe the spectrum of ATP7B variants and assess their clinical effects in the Han Chinese population. Methods: The ATP7B gene was directly sequenced in 632 unrelated WD patients and 503 unrelated healthy individuals. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Different frequency of variants observed in both cases and controls were tested using Chi-square or Fisher's exact tests. Results: We detected 161 non-synonymous variants in these 632 WD patients, 58 of which were novel. Among these variants, 78, 64, 8, 4, and 7 were classified as 'pathogenic variants', 'likely pathogenic variants', 'variants with uncertain significance', 'likely benign variants', and 'benign variants', respectively. Ninety percent (569/632) of these WD patients can be genetically diagnosed with two or more 'pathogenic' or 'likely pathogenic' variants. The 14 most common disease-causing variants were found at least once in 94% (537/569) of genetically diagnosed patients. Conclusions: These data expand the spectrum of ATP7B variants and facilitate effective screening for ATP7B variants for early diagnosis of WD and development of individualized treatment regimens. PMID:27022412

  11. Optimization of Blade Stiffened Composite Panel under Buckling and Strength Constraints

    NASA Astrophysics Data System (ADS)

    Todoroki, Akira; Sekishiro, Masato

    This paper deals with multiple constraints for dimension and stacking-sequence optimization of a blade-stiffened composite panel. In a previous study, a multiple objective genetic algorithm using a Kriging response surface with a buckling load constraint was the target. The present study focuses on dimension and stacking-sequence optimization with both a buckling load constraint and a fracture constraint. Multiple constraints complicate the process of selecting sampling analyses to improve the Kriging response surface. The proposed method resolves this problem using the most-critical-constraint approach. The new approach is applied to a blade stiffened composite panel and the approach is shown to be efficient.

  12. 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

    2015-01-01

    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. PMID:26681043

  13. Pediatric genetic disorders of lens

    PubMed Central

    Nihalani, Bharti R.

    2014-01-01

    Pediatric genetic disorders of lens include various cataractous and non-cataractous anomalies. The purpose of this review is to help determine the genetic cause based on the lens appearance, ocular and systemic associations. Children with bilateral cataracts require a comprehensive history, ophthalmic and systemic examination to guide further genetic evaluation. With advancements in genetics, it is possible to determine the genetic mutations and assess phenotype genotype correlation in different lens disorders. The genetic diagnosis helps the families to better understand the disorder and develop realistic expectations as to the course of their child's disorder.

  14. Constraints complicate centrifugal compressor depressurization

    SciTech Connect

    Key, B. ); Colbert, F.L. )

    1993-05-10

    Blowdown of a centrifugal compressor is complicated by process constraints that might require slowing the depressurization rate and by mechanical constraints for which a faster rate might be preferred. The paper describes design constraints such as gas leaks; thrust-bearing overload; system constraints; flare extinguishing; heat levels; and pressure drop.

  15. 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

  16. 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.

  17. 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

  18. Breaking evolutionary constraint with a tradeoff ratchet.

    PubMed

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

    2015-12-01

    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

  19. 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

  20. Colostomy Guide

    MedlinePlus

    ... window. My Saved Articles » My ACS » Colostomy: A Guide Download Printable Version [PDF] » ( En español ) Colostomy surgery ... the activities you enjoyed in the past. This guide will help you better understand colostomy – what it ...

  1. 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. PMID:24921605

  2. 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.

  3. 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.

  4. Optimizing selection with several constraints in poultry breeding.

    PubMed

    Chapuis, H; Pincent, C; Colleau, J J

    2016-02-01

    Poultry breeding schemes permanently face the need to control the evolution of coancestry and some critical traits, while selecting for a main breeding objective. The main aims of this article are first to present an efficient selection algorithm adapted to this situation and then to measure how the severity of constraints impacted on the degree of loss for the main trait, compared to BLUP selection on the main trait, without any constraint. Broiler dam and sire line schemes were mimicked by simulation over 10 generations and selection was carried out on the main trait under constraints for coancestry and for another trait, antagonistic with the main trait. The selection algorithm was a special simulated annealing (adaptative simulated annealing (ASA)). It was found to be rapid and able to meet constraints very accurately. A constraint on the second trait was found to induce an impact similar to or even greater than the impact of the constraint on coancestry. The family structure of selected poultry populations made it easy to control the evolution of coancestry at a reasonable cost but was not as useful for reducing the cost of controlling evolution of the antagonistic traits. Multiple constraints impacted almost additively on the genetic gain for the main trait. Adding constraints for several traits would therefore be justified in real life breeding schemes, possibly after evaluating their impact through simulated annealing. PMID:26220593

  5. 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.

  6. 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.

  7. 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.

  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. PMID:27067213

  9. 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.

  10. 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.

  11. A Novel Constraint for Thermodynamically Designing DNA Sequences

    PubMed Central

    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. PMID:24015217

  12. 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. PMID:24015217

  13. 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.

  14. 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.

  15. Superresolution via sparsity constraints

    NASA Technical Reports Server (NTRS)

    Donoho, David L.

    1992-01-01

    The problem of recovering a measure mu supported on a lattice of span Delta is considered under the condition that measurements are only available concerning the Fourier Transform at frequencies of Omega or less. If Omega is much smaller than the Nyquist frequency pi/Delta and the measurements are noisy, then stable recovery of mu is generally impossible. It is shown here that if, in addition, it is known that mu satisfies certain sparsity constraints, then stable recovery is possible. This finding validates practical efforts in spectroscopy, seismic prospecting, and astronomy to provide superresolution by imposing support limitations in reconstruction.

  16. 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.

  17. Sequestration of atmospheric CO2 in a weathering-derived, serpentinite-hosted magnesite deposit: 14C tracing of carbon sources and age constraints for a refined genetic model

    NASA Astrophysics Data System (ADS)

    Oskierski, H. C.; Dlugogorski, B. Z.; Jacobsen, G.

    2013-12-01

    geochemical signatures indicate that weathering is the integral magnesite mineralisation process at Attunga. Conventional radiocarbon ages of about 50 ka represent a maximum age constraint for the formation of the magnesite deposit during Quaternary weathering. A significant amount of atmospheric CO2 has been sequestered via the biosphere and carbonation of serpentinite at Attunga.

  18. 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.

  19. FIELD GUIDE EFFICACY IN THE IDENTIFICATION OF REALLOCATED CLONALLY PROPAGATED ACCESSIONS OF CACAO (THEOBROMA CACAO L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Misidentification of germplasm presents a major constraint to cacao cultivar development. Misidentification of parents has impeded resolution of the genetic basis for agronomic traits as mixtures of genotypes produce inconsistent results and conflicting genetic estimates resulting in slow progress i...

  20. Geochemical and isotopic studies of the Lady of the Lake Intrusion and associated tobacco root Batholith: Constraints on the genetic relation between Cretaceous mafic and silicic magmatism in Southwestern Montana

    NASA Astrophysics Data System (ADS)

    Sarkar, Arindam; Brophy, James G.; Ripley, Edward M.; Li, Chusi; Kamo, Sandra L.

    2009-12-01

    Small volumes of alkalic mafic intrusions are spatially associated with Cretaceous to Early Tertiary granodioritic to granitic intrusions in the batholithic province of southwestern Montana. The mafic rocks generally occur near the contacts of the Boulder, Pioneer, and Tobacco Root Batholiths with country rocks, but their genetic relation with the batholiths is uncertain. The Lady of the Lake Intrusion is a small layered body composed of melagabbro and gabbro that occurs along the south-central margin of the Tobacco Root Batholith near its contact with Archean country rocks. A diorite unit, spatially distinct from the granodiorite/quartz monzonite of the Batholith intrudes the gabbroic rocks of the Lady of the Lake Intrusion. Zircon crystals from the melagabbro and diorite units give U-Pb ages that are very similar to that of the Tobacco Root Batholith at 74.88 ± 0.17 Ma and 76.24 ± 0.08 Ma, respectively. Mineral chemistry, whole rock major and trace element compositions, and oxygen and sulfur isotope ratios have been utilized to evaluate the genetic relation between the Lady of the Lake Intrusion, the diorite, and the Tobacco Root Batholith. No significant variation in the composition of clinopyroxene is observed in different rock units of the Lady of the Lake Intrusion. Minor olivine with Fo 64 in the melagabbro unit is interpreted to represent early crystallization in the base of the intrusion. Whole rock major and trace element compositions, as well as results from modeling using the MELTS program, are consistent with the premise that the diorite was produced by fractional crystallization of the same magma that was parental to the gabbros of the Lady of the Lake Intrusion. Both whole rock chemistry and oxygen isotopes support the interpretation that the parental magma was an uncontaminated mantle-derived basaltic magma. In contrast, trace element and oxygen isotopes indicate that the quartz monzonitic and granodioritic rocks of the Tobacco Root Batholith and

  1. Genetics Home Reference: carbamoyl phosphate synthetase I deficiency

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions carbamoyl phosphate synthetase I deficiency ...

  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. 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…

  6. Coatings Guide

    EPA Science Inventory

    The Coatings Guide is a free online information resource that focuses on alternative, low-emission coatings for metal, plastic, and architectural substrates. Developed cooperatively by the U.S. EPA's Office of Research and Development and Research Triangle Institute (RTI) Interna...

  7. Medication Guide

    MedlinePlus

    ... Quit Smoking Benefits of Quitting Health Effects of Smoking Secondhand Smoke Withdrawal Ways to Quit QuitGuide Pregnancy & Motherhood Pregnancy & Motherhood Before Your Baby is Born From Birth to 2 Years Quitting for Two SmokefreeMom Healthy Kids Parenting & ... Weight Management Weight Management ...

  8. 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;…

  9. 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.

  10. 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.

  11. Seismological Constraints on Geodynamics

    NASA Astrophysics Data System (ADS)

    Lomnitz, C.

    2004-12-01

    Earth is an open thermodynamic system radiating heat energy into space. A transition from geostatic earth models such as PREM to geodynamical models is needed. We discuss possible thermodynamic constraints on the variables that govern the distribution of forces and flows in the deep Earth. In this paper we assume that the temperature distribution is time-invariant, so that all flows vanish at steady state except for the heat flow Jq per unit area (Kuiken, 1994). Superscript 0 will refer to the steady state while x denotes the excited state of the system. We may write σ 0=(J{q}0ṡX{q}0)/T where Xq is the conjugate force corresponding to Jq, and σ is the rate of entropy production per unit volume. Consider now what happens after the occurrence of an earthquake at time t=0 and location (0,0,0). The earthquake introduces a stress drop Δ P(x,y,z) at all points of the system. Response flows are directed along the gradients toward the epicentral area, and the entropy production will increase with time as (Prigogine, 1947) σ x(t)=σ 0+α {1}/(t+β )+α {2}/(t+β )2+etc A seismological constraint on the parameters may be obtained from Omori's empirical relation N(t)=p/(t+q) where N(t) is the number of aftershocks at time t following the main shock. It may be assumed that p/q\\sim\\alpha_{1}/\\beta times a constant. Another useful constraint is the Mexican-hat geometry of the seismic transient as obtained e.g. from InSAR radar interferometry. For strike-slip events such as Landers the distribution of \\DeltaP is quadrantal, and an oval-shaped seismicity gap develops about the epicenter. A weak outer triggering maxiμm is found at a distance of about 17 fault lengths. Such patterns may be extracted from earthquake catalogs by statistical analysis (Lomnitz, 1996). Finally, the energy of the perturbation must be at least equal to the recovery energy. The total energy expended in an aftershock sequence can be found approximately by integrating the local contribution over

  12. Genetics Home Reference: isolated Pierre Robin sequence

    MedlinePlus

    ... of isolated Pierre Robin sequence: Boston Children's Hospital: Cleft Lip and Cleft Palate Treatment and Care Genetic Testing ... 7 links) Centers for Disease Control: Facts About Cleft Lip and Cleft Palate Children's Craniofacial Association: A Guide ...

  13. Genetic and Rare Diseases Information Center

    MedlinePlus

    ... and Students guides/pages/99/teachers-and-students Teaching Resources News 1 In The Spotlight News Archive ... about rare or genetic diseases in English or Spanish. text go Browse Diseases View diseases by alphabetical ...

  14. Genetic Counseling

    MedlinePlus

    ... Articles Genetic Counseling Information For... Media Policy Makers Genetic Counseling Language: English Español (Spanish) Recommend on Facebook ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  15. New Genetics

    MedlinePlus

    ... human genome, behavioral genetics, pharmacogenetics, drug resistance, biofilms, computer modeling. » more Chapter 5: 21st-Century Genetics Covers systems biology, GFP, genetic testing, privacy concerns, DNA forensics, ...

  16. 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…

  17. 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…

  18. 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.

  19. Modeling and analysis of rigid multibody systems with driving constraints and frictional translation joints

    NASA Astrophysics Data System (ADS)

    Zhuang, Fang-Fang; Wang, Qi

    2014-06-01

    An approach is proposed for modeling and analyses of rigid multibody systems with frictional translation joints and driving constraints. The geometric constraints of translational joints with small clearance are treated as bilateral constraints by neglecting the impact between sliders and guides. Firstly, the normal forces acting on sliders, the driving constraint forces (or moments) and the constraint forces of smooth revolute joints are all described by complementary conditions. The frictional contacts are characterized by a setvalued force law of Coulomb's dry friction. Combined with the theory of the horizontal linear complementarity problem (HLCP), an event-driven scheme is used to detect the transitions of the contact situation between sliders and guides, and the stick-slip transitions of sliders, respectively. And then, all constraint forces in the system can be computed easily. Secondly, the dynamic equations of multibody systems are written at the acceleration-force level by the Lagrange multiplier technique, and the Baumgarte stabilization method is used to reduce the constraint drift. Finally, a numerical example is given to show some non-smooth dynamical behaviors of the studied system. The obtained results validate the feasibility of algorithm and the effect of constraint stabilization.

  20. 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

  1. 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

  2. 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}

  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. Canali-type channels on Venus - Some genetic constraints

    NASA Technical Reports Server (NTRS)

    Komatsu, Goro; Kargel, Jeffrey S.; Baker, Victor R.

    1992-01-01

    Canali-type channels on Venus are unique because of their great lengths (up to 6800 km) and nearly constant channel cross sectional shapes along their paths. A simple model incorporating channel flow and radiative cooling suggests that common terrestrial-type tholeiite lava cannot sustain a superheated and turbulent state for the long distances required for thermal erosion of canali within allowable discharge rates. If canali formed mainly by constructional processes, laminar tholeiitic flow of relatively high, sustained discharge rates might travel the observed distances, but the absence of levees would need to be explained. An exotic low temperature, low viscosity lava like carbonatite or sulfur seems to be required for the erosional genesis of canali.

  5. Integrated Science--Reasons & Constraints.

    ERIC Educational Resources Information Center

    Fox, M.; Oliver, P. M.

    1978-01-01

    Describes the philosophy and development of an integrated science program in a British secondary school. Discusses constraints to the program including laboratory facilities, money, and fewer laboratory technicians. (MA)

  6. Fluid convection, constraint and causation

    PubMed Central

    Bishop, Robert C.

    2012-01-01

    Complexity—nonlinear dynamics for my purposes in this essay—is rich with metaphysical and epistemological implications but is receiving sustained philosophical analysis only recently. I will explore some of the subtleties of causation and constraint in Rayleigh–Bénard convection as an example of a complex phenomenon, and extract some lessons for further philosophical reflection on top-down constraint and causation particularly with respect to causal foundationalism. PMID:23386955

  7. 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. PMID:25380338

  8. 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,…

  9. Genetic disorders producing compressive radiculopathy.

    PubMed

    Corey, Joseph M

    2006-11-01

    Back pain is a frequent complaint seen in neurological practice. In evaluating back pain, neurologists are asked to evaluate patients for radiculopathy, determine whether they may benefit from surgery, and help guide management. Although disc herniation is the most common etiology of compressive radiculopathy, there are many other causes, including genetic disorders. This article is a discussion of genetic disorders that cause or contribute to radiculopathies. These genetic disorders include neurofibromatosis, Paget's disease of bone, and ankylosing spondylitis. Numerous genetic disorders can also lead to deformities of the spine, including spinal muscular atrophy, Friedreich's ataxia, Charcot-Marie-Tooth disease, familial dysautonomia, idiopathic torsional dystonia, Marfan's syndrome, and Ehlers-Danlos syndrome. However, the extent of radiculopathy caused by spine deformities is essentially absent from the literature. Finally, recent investigation into the heritability of disc degeneration and lumbar disc herniation suggests a significant genetic component in the etiology of lumbar disc disease. PMID:17048153

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. Genetic counseling

    MedlinePlus

    Genetics is the study of heredity, the process of a parent passing certain genes on to their ... certain diseases are also often determined by genes. Genetic counseling is the process where parents can learn ...

  14. 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

  15. 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

  16. Data assimilation with inequality constraints

    NASA Astrophysics Data System (ADS)

    Thacker, W. C.

    If values of variables in a numerical model are limited to specified ranges, these restrictions should be enforced when data are assimilated. The simplest option is to assimilate without regard for constraints and then to correct any violations without worrying about additional corrections implied by correlated errors. This paper addresses the incorporation of inequality constraints into the standard variational framework of optimal interpolation with emphasis on our limited knowledge of the underlying probability distributions. Simple examples involving only two or three variables are used to illustrate graphically how active constraints can be treated as error-free data when background errors obey a truncated multi-normal distribution. Using Lagrange multipliers, the formalism is expanded to encompass the active constraints. Two algorithms are presented, both relying on a solution ignoring the inequality constraints to discover violations to be enforced. While explicitly enforcing a subset can, via correlations, correct the others, pragmatism based on our poor knowledge of the underlying probability distributions suggests the expedient of enforcing them all explicitly to avoid the computationally expensive task of determining the minimum active set. If additional violations are encountered with these solutions, the process can be repeated. Simple examples are used to illustrate the algorithms and to examine the nature of the corrections implied by correlated errors.

  17. 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. PMID:23569298

  18. 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.

  19. 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...

  20. Genetic evaluation of male infertility

    PubMed Central

    2014-01-01

    Men with severe oligospermia (<5 million sperm/mL ejaculate fluid) or azoospermia should receive genetic testing to clarify etiology of male infertility prior to treatment. Categorization by obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is critical since genetic testing differs for the former with normal testicular function, testicular volume (~20 mL), and follicle-stimulating hormone (FSH) (1-8 IU/mL) when compared to the latter with small, soft testes and increased FSH. History and physician examination along with laboratory testing (following appropriate genetic counseling) is critical to accurate selection of genetic testing appropriate for azoospermia due to primary testicular failure as compared with congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be warranted depending on the clinical context of severe oligospermia or NOA. The results of genetic testing guide management options. The most recent techniques for genetic analysis, including sperm microRNA (miRNA) and epigenetics, are forming the foundation for future genetic diagnosis and therapeutic targets in male infertility. PMID:26813518

  1. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Genetics and genetic testing of dilated cardiomyopathy: a new perspective.

    PubMed

    Mestroni, Luisa; Taylor, Matthew R G

    2013-01-01

    The completion of the Human Genome Project was a landmark achievement, but as clinical genetic testing becomes more mainstream, the extent of remarkable genetic variation is increasingly being appreciated. Newer DNA sequencing technology can now complete the sequencing of an entire human genome several times over in a matter of days, but this will undoubtedly add new challenges to the difficulty of distinguishing true pathogenic variants from benign variants in diagnostic genetics and in the research setting. The recent discovery of the role of titin gene (TTN) mutations in dilated cardiomyopathy (DCM) will make genetic testing in this disease more efficient. Furthermore, better understanding of genotype-phenotype associations will assist clinicians in identifying early stages of disease and providing more appropriate treatments. This high level of complexity requires an expert genetic team to offer counseling and to manage, deliver, and follow-up over time the results of genetic testing, which is particularly important for screening of family members potentially at risk. In DCM, genetic testing may be useful for the identification of non-carriers and asymptomatic carriers, as well as for prevention strategies, sport recommendations, and defibrillator implantation. It can also guide reproductive decision-making including utilization of pre-implantation genetic diagnostic strategies. PMID:23375013

  4. 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.

  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. 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.

  7. Perceptual Constraints in Phonotactic Learning

    ERIC Educational Resources Information Center

    Endress, Ansgar D.; Mehler, Jacques

    2010-01-01

    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…

  8. Contextual Constraints on Adolescents' Leisure.

    ERIC Educational Resources Information Center

    Silbereisen, Rainer K.

    2003-01-01

    Interlinks crucial cultural themes emerging from preceding chapters, highlighting the contextual constraints in adolescents' use of free time. Draws parallels across the nations discussed on issues related to how school molds leisure time, the balance of passive versus active leisure, timing of leisure pursuits, and the cumulative effect of…

  9. 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.

  10. 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.

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

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions CADASIL cerebral autosomal dominant arteriopathy ...

  12. Constraint Handling in Transmission Network Expansion Planning

    NASA Astrophysics Data System (ADS)

    Mallipeddi, R.; Verma, Ashu; Suganthan, P. N.; Panigrahi, B. K.; Bijwe, P. R.

    Transmission network expansion planning (TNEP) is a very important and complex problem in power system. Recently, the use of metaheuristic techniques to solve TNEP is gaining more importance due to their effectiveness in handling the inequality constraints and discrete values over the conventional gradient based methods. Evolutionary algorithms (EAs) generally perform unconstrained search and require some additional mechanism to handle constraints. In EA literature, various constraint handling techniques have been proposed. However, to solve TNEP the penalty function approach is commonly used while the other constraint handling methods are untested. In this paper, we evaluate the performance of different constraint handling methods like Superiority of Feasible Solutions (SF), Self adaptive Penalty (SP),E-Constraint (EC), Stochastic Ranking (SR) and the ensemble of constraint handling techniques (ECHT) on TNEP. The potential of different constraint handling methods and their ensemble is evaluated using an IEEE 24 bus system with and without security constraints.

  13. Future directions in genetic counseling: practical and ethical considerations.

    PubMed

    Biesecker, Barbara Bowles

    1998-06-01

    The accelerated discovery of gene mutations that lead to increased risk of disease has led to the rapid development of predictive genetic tests. These tests improve the accuracy of assigning risk, but at a time when intervention or prevention strategies are largely unproved. In coming years, however, data will become increasingly available to guide treatment of genetic diseases. Eventually genetic testing will be performed for common diseases as well as for rare genetic conditions. This will challenge genetic counseling practice. The ethical principles that now guide this practice take into account the personal nature of test decision making, the need to respect individual self-determination, and the importance of client confidentiality. Certain of these principles may have to be modified as genetic testing becomes more widespread in order to meet the changing needs of clients and society. This paper offers recommendations to ensure that genetic counselors will take a leading role in the future delivery of ethical genetic services. PMID:11657426

  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. Evolutionary constraints and the maintenance of individual specialization throughout succession.

    PubMed

    Monro, Keyne; Marshall, Dustin J

    2013-12-01

    Constraints on life-history traits, with their close links to fitness, are widely invoked as limits to niche expansion at most organizational levels. Theoretically, such constraints can maintain individual specialization by preventing adaptation to all niches available, but empirical evidence of them remains elusive for natural populations. This problem may be compounded by a tendency to seek constraints involving multiple traits, neglecting their added potential to manifest in trait expression across environments (i.e., within reaction norms). By replicating genotypes of a colonial marine invertebrate across successional stages in its local community, and taking a holistic approach to the analysis of ensuing reaction norms for fitness, we show the potential for individual specialization to be maintained by genetic constraints associated with these norms, which limit the potential for fitness at one successional stage to improve without loss of fitness at others. Our study provides new insight into the evolutionary maintenance of individual specialization in natural populations and reinforces the importance of reaction norms for studying this phenomenon. PMID:24299414

  16. Stress constraints in optimality criteria design

    NASA Technical Reports Server (NTRS)

    Levy, R.

    1982-01-01

    Procedures described emphasize the processing of stress constraints within optimality criteria designs for low structural weight with stress and compliance constraints. Prescreening criteria are used to partition stress constraints into either potentially active primary sets or passive secondary sets that require minimal processing. Side constraint boundaries for passive constraints are derived by projections from design histories to modify conventional stress-ratio boundaries. Other procedures described apply partial structural modification reanalysis to design variable groups to correct stress constraint violations of unfeasible designs. Sample problem results show effective design convergence and, in particular, advantages for reanalysis in obtaining lower feasible design weights.

  17. 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.

  18. Integrating Guided Inquiry into a Traditional Chemistry Curricular Framework

    ERIC Educational Resources Information Center

    Smithenry, Dennis William

    2010-01-01

    The case study presented in this paper examines the work of one high school chemistry teacher who has integrated guided inquiry into a yearlong, traditional curricular framework in ways that take into account the constraints and realities of her classroom. The study's findings suggest (1) the extent and frequency to which teachers can…

  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. PMID:23886651

  20. GA-Based Image Restoration by Isophote Constraint Optimization

    NASA Astrophysics Data System (ADS)

    Kim, Jong Bae; Kim, Hang Joon

    2003-12-01

    We propose an efficient technique for image restoration based on a genetic algorithm (GA) with an isophote constraint. In our technique, the image restoration problem is modeled as an optimization problem which, in our case, is solved by a cost function with isophote constraint that is minimized using a GA. We consider that an image is decomposed into isophotes based on connected components of constant intensity. The technique creates an optimal connection of all pairs of isophotes disconnected by a caption in the frame. For connecting the disconnected isophotes, we estimate the value of the smoothness, given by the best chromosomes of the GA and project this value in the isophote direction. Experimental results show a great possibility for automatic restoration of a region in an advertisement scene.

  1. Unitarity constraints on trimaximal mixing

    SciTech Connect

    Kumar, Sanjeev

    2010-07-01

    When the neutrino mass eigenstate {nu}{sub 2} is trimaximally mixed, the mixing matrix is called trimaximal. The middle column of the trimaximal mixing matrix is identical to tribimaximal mixing and the other two columns are subject to unitarity constraints. This corresponds to a mixing matrix with four independent parameters in the most general case. Apart from the two Majorana phases, the mixing matrix has only one free parameter in the CP conserving limit. Trimaximality results in interesting interplay between mixing angles and CP violation. A notion of maximal CP violation naturally emerges here: CP violation is maximal for maximal 2-3 mixing. Similarly, there is a natural constraint on the deviation from maximal 2-3 mixing which takes its maximal value in the CP conserving limit.

  2. 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.

  3. 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.

  4. 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)

  5. Isocurvature constraints on portal couplings

    NASA Astrophysics Data System (ADS)

    Kainulainen, Kimmo; Nurmi, Sami; Tenkanen, Tommi; Tuominen, Kimmo; Vaskonen, Ville

    2016-06-01

    We consider portal models which are ultraweakly coupled with the Standard Model, and confront them with observational constraints on dark matter abundance and isocurvature perturbations. We assume the hidden sector to contain a real singlet scalar s and a sterile neutrino ψ coupled to s via a pseudoscalar Yukawa term. During inflation, a primordial condensate consisting of the singlet scalar s is generated, and its contribution to the isocurvature perturbations is imprinted onto the dark matter abundance. We compute the total dark matter abundance including the contributions from condensate decay and nonthermal production from the Standard Model sector. We then use the Planck limit on isocurvature perturbations to derive a novel constraint connecting dark matter mass and the singlet self coupling with the scale of inflation: mDM/GeV lesssim 0.2λs3/8 (H*/1011 GeV)‑3/2. This constraint is relevant in most portal models ultraweakly coupled with the Standard Model and containing light singlet scalar fields.

  6. 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.

  7. Analysis of Space Tourism Constraints

    NASA Astrophysics Data System (ADS)

    Bonnal, Christophe

    2002-01-01

    Space tourism appears today as a new Eldorado in a relatively near future. Private operators are already proposing services for leisure trips in Low Earth Orbit, and some happy few even tested them. But are these exceptional events really marking the dawn of a new space age ? The constraints associated to the space tourism are severe : - the economical balance of space tourism is tricky; development costs of large manned - the technical definition of such large vehicles is challenging, mainly when considering - the physiological aptitude of passengers will have a major impact on the mission - the orbital environment will also lead to mission constraints on aspects such as radiation, However, these constraints never appear as show-stoppers and have to be dealt with pragmatically: - what are the recommendations one can make for future research in the field of space - which typical roadmap shall one consider to develop realistically this new market ? - what are the synergies with the conventional missions and with the existing infrastructure, - how can a phased development start soon ? The paper proposes hints aiming at improving the credibility of Space Tourism and describes the orientations to follow in order to solve the major hurdles found in such an exciting development.

  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. 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.

  10. Genetic counseling.

    PubMed

    Fraser, F C

    1974-09-01

    A workshop was sponsored by the National Genetics Foundation to evaluate and make recommendations about the status of genetic counseling, its goals, nature, achievements, and needs. The process of genetic workup and counseling is divided into 5 stages: validation of the diagnosis; obtaining family history; estimation of the risk of recurrence; helping the family make a decision and take appropriate action; and extending counseling to other members of the family. Counseling can be directed at individuals or at special groups with the potential of carrying such diseases as sickle cell amenia or Tay-Sachs. No consensus exists on an optimal counseling approach. Genetic counseling is regarded as a team effort, requiring, in addition to the counselor, laboratory facilities and a variety of specialists. The source of payment for genetic counseling services is regarded as a problem of increasing concern. Generally, the fee paid rarely covers the cost of the many procedures and it is suggested that the cost, like that of other public health services, should be subsidized by the state. Considerable argument exists over whether a genetic counselor must have a M.D. degree or whether a Ph. D. in medical genetics is suitable enough. The quality of much genetic counseling, which is often done in the office of doctors unskilled in the field, would be increased if better training in genetics were offered to medical students and if physicians were informed of the existence of counseling centers. Further, there is a growing feeling that some sort of accreditation of genetic counselors is desirable. PMID:4609197

  11. 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

  12. 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.

  13. Organizational Constraints on Corporate Public Relations Practitioners.

    ERIC Educational Resources Information Center

    Ryan, Michael

    1987-01-01

    Catalogs various internal constraints under which many public relations practitioners work, including constraints on (1) access to management; (2) information collection; (3) dissemination of timely, accurate information; and (4) the public relations mission. Reports that most practitioners see organizational constraints as more of a problem for…

  14. Identification Constraints and Inference in Factor Models

    ERIC Educational Resources Information Center

    Loken, Eric

    2005-01-01

    The choice of constraints used to identify a simple factor model can affect the shape of the likelihood. Specifically, under some nonzero constraints, standard errors may be inestimable even at the maximum likelihood estimate (MLE). For a broader class of nonzero constraints, symmetric normal approximations to the modal region may not be…

  15. Cultural and Social Constraints on Portability.

    ERIC Educational Resources Information Center

    Murray-Lasso, Marco

    1990-01-01

    Describes 12 constraints imposed by culture on educational software portability. Nielsen's seven-level virtual protocol model of human-computer interaction is discussed as a framework for considering the constraints, a hypothetical example of adapting software for Mexico is included, and suggestions for overcoming constraints and making software…

  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. 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…

  18. Genetic events in the pathogenesis of multiple myeloma

    PubMed Central

    Chng, W. J.; Glebov, O.; Bergsagel, P.L.; Kuehl, W. M.

    2007-01-01

    The genetics of myeloma has been increasingly elucidated in recent years. Recurrent genetic events, and also biologically distinct and clinically relevant genetic subtypes of myeloma have been defined. This has facilitated our understanding of the molecular pathogenesis of the disease. In addition, some genetic abnormalities have proved to be highly reproducible prognostic factors. With the expanding therapeutic armamentarium, it is time to include genetic assessment as part of clinical evaluation of myeloma patients to guide management. In this review we examine the role of various genetic abnormalities in the molecular pathogenesis of myeloma, and the use of such abnormalities in disease classification, prognosis and clinical management. PMID:18070707

  19. Genetic events in the pathogenesis of multiple myeloma.

    PubMed

    Chng, W J; Glebov, O; Bergsagel, P L; Kuehl, W M

    2007-12-01

    The genetics of myeloma has been increasingly elucidated in recent years. Recurrent genetic events, and also biologically distinct and clinically relevant genetic subtypes of myeloma have been defined. This has facilitated our understanding of the molecular pathogenesis of the disease. In addition, some genetic abnormalities have proved to be highly reproducible prognostic factors. With the expanding therapeutic armamentarium, it is time to include genetic assessment as part of clinical evaluation of myeloma patients to guide management. In this review we examine the role of various genetic abnormalities in the molecular pathogenesis of myeloma, and the use of such abnormalities in disease classification, prognosis and clinical management. PMID:18070707

  20. Guide to Understanding Lymphedema

    MedlinePlus

    ... Diet, Nutrition and Exercise Expressive Writing Guided Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and ... Diet, Nutrition and Exercise Expressive Writing Guided Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and ...

  1. 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

  2. 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

  3. 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…

  4. ESL VI Curriculum Guide.

    ERIC Educational Resources Information Center

    Flander, Leonard

    This curriculum guide for English as a Second Language (ESL) Level VI is the sixth of six in a Guam Community College ESL project series. The other five guides, a companion teacher's guide and pre- and post-tests are available separately (see note). The entire project centers around the Peabody Kits P, Level P, Level 1, Level 2, Level 3, and the…

  5. [Tennessee Kindergarten Curriculum Guides.

    ERIC Educational Resources Information Center

    Tennessee State Dept. of Education, Nashville.

    Provided are Tennessee's state kindergarten curriculum guides in the 6 areas of health, social studies, language arts, science, physical education, and mathematics. The health curriculum guide centers on developing and maintaining good health. The social studies guide aids children in understanding self as an individual and in relation to other…

  6. ESL V Curriculum Guide.

    ERIC Educational Resources Information Center

    Flander, Leonard

    This curriculum guide for English as a Second Language (ESL) Level V is the fifth of six in the Guam Community College ESL project series. The other five guides, a companion teacher's guide, and pre- and post-tests are available separately (see note). The entire project centers around the Peabody Kits P, Level P, Level 1, Level 2, Level 3, and the…

  7. 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…

  8. SMIP Chemistry Curriculum Guides.

    ERIC Educational Resources Information Center

    Wilkes Coll., Wilkes-Barre, PA.

    Included are most guides for a one-year course in senior high school chemistry. The guides may be interchanged at the teacher's discretion, following any text sequence or course outline. Each guide consists of six sections: (1) an approach, which briefly discusses the unit in terms of background material, pitfalls to be avoided, and suggested…

  9. Genetics of inherited cardiomyopathy

    PubMed Central

    Jacoby, Daniel; McKenna, William J.

    2012-01-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype–phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young. PMID:21810862

  10. 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.