Science.gov

Sample records for define utility functions

  1. Different methods to define utility functions yield similar results but engage different neural processes.

    PubMed

    Heldmann, Marcus; Vogt, Bodo; Heinze, Hans-Jochen; Münte, Thomas F

    2009-01-01

    Although the concept of utility is fundamental to many economic theories, up to now a generally accepted method determining a subject's utility function is not available. We investigated two methods that are used in economic sciences for describing utility functions by using response-locked event-related potentials in order to assess their neural underpinnings. For determining the certainty equivalent, we used a lottery game with probabilities to win p = 0.5, for identifying the subjects' utility functions directly a standard bisection task was applied. Although the lottery tasks' payoffs were only hypothetical, a pronounced negativity was observed resembling the error related negativity (ERN) previously described in action monitoring research, but this occurred only for choices far away from the indifference point between money and lottery. By contrast, the bisection task failed to evoke an remarkable ERN irrespective of the responses' correctness. Based on these findings we are reasoning that only decisions made in the lottery task achieved a level of subjective relevance that activates cognitive-emotional monitoring. In terms of economic sciences, our findings support the view that the bisection method is unaffected by any kind of probability valuation or other parameters related to risk and in combination with the lottery task can, therefore, be used to differentiate between payoff and probability valuation. PMID:19893764

  2. Model-based Utility Functions

    NASA Astrophysics Data System (ADS)

    Hibbard, Bill

    2012-05-01

    Orseau and Ring, as well as Dewey, have recently described problems, including self-delusion, with the behavior of agents using various definitions of utility functions. An agent's utility function is defined in terms of the agent's history of interactions with its environment. This paper argues, via two examples, that the behavior problems can be avoided by formulating the utility function in two steps: 1) inferring a model of the environment from interactions, and 2) computing utility as a function of the environment model. Basing a utility function on a model that the agent must learn implies that the utility function must initially be expressed in terms of specifications to be matched to structures in the learned model. These specifications constitute prior assumptions about the environment so this approach will not work with arbitrary environments. But the approach should work for agents designed by humans to act in the physical world. The paper also addresses the issue of self-modifying agents and shows that if provided with the possibility to modify their utility functions agents will not choose to do so, under some usual assumptions.

  3. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  4. Time Functions as Utilities

    NASA Astrophysics Data System (ADS)

    Minguzzi, E.

    2010-09-01

    Every time function on spacetime gives a (continuous) total preordering of the spacetime events which respects the notion of causal precedence. The problem of the existence of a (semi-)time function on spacetime and the problem of recovering the causal structure starting from the set of time functions are studied. It is pointed out that these problems have an analog in the field of microeconomics known as utility theory. In a chronological spacetime the semi-time functions correspond to the utilities for the chronological relation, while in a K-causal (stably causal) spacetime the time functions correspond to the utilities for the K + relation (Seifert’s relation). By exploiting this analogy, we are able to import some mathematical results, most notably Peleg’s and Levin’s theorems, to the spacetime framework. As a consequence, we prove that a K-causal (i.e. stably causal) spacetime admits a time function and that the time or temporal functions can be used to recover the K + (or Seifert) relation which indeed turns out to be the intersection of the time or temporal orderings. This result tells us in which circumstances it is possible to recover the chronological or causal relation starting from the set of time or temporal functions allowed by the spacetime. Moreover, it is proved that a chronological spacetime in which the closure of the causal relation is transitive (for instance a reflective spacetime) admits a semi-time function. Along the way a new proof avoiding smoothing techniques is given that the existence of a time function implies stable causality, and a new short proof of the equivalence between K-causality and stable causality is given which takes advantage of Levin’s theorem and smoothing techniques.

  5. Spaces defined by the Paley function

    SciTech Connect

    Astashkin, S V; Semenov, E M

    2013-07-31

    The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

  6. Speciation without Pre-Defined Fitness Functions

    PubMed Central

    Gras, Robin; Golestani, Abbas; Hendry, Andrew P.; Cristescu, Melania E.

    2015-01-01

    The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions. PMID:26372462

  7. Wigner functions defined with Laplace transform kernels.

    PubMed

    Oh, Se Baek; Petruccelli, Jonathan C; Tian, Lei; Barbastathis, George

    2011-10-24

    We propose a new Wigner-type phase-space function using Laplace transform kernels--Laplace kernel Wigner function. Whereas momentum variables are real in the traditional Wigner function, the Laplace kernel Wigner function may have complex momentum variables. Due to the property of the Laplace transform, a broader range of signals can be represented in complex phase-space. We show that the Laplace kernel Wigner function exhibits similar properties in the marginals as the traditional Wigner function. As an example, we use the Laplace kernel Wigner function to analyze evanescent waves supported by surface plasmon polariton.

  8. Defining the Functions of Public Health Governance

    PubMed Central

    Carlson, Valeria; Chilton, Marita J.; Corso, Liza C.; Beitsch, Leslie M.

    2015-01-01

    We conducted a literature review in 2011 to determine if accepted governance functions continue to reflect the role of public health governing entities. Reviewing literature and other source documents, as well as consulting with practitioners, resulted in an iterative process that identified 6 functions of public health governance and established definitions for each of these: policy development; resource stewardship; continuous improvement; partner engagement; legal authority; and oversight of a health department. These functions provided context for the role of governing entities in public health practice and aligned well with existing public health accreditation standards. Public health systems research can build from this work in future explorations of the contributions of governance to health department performance. PMID:25689187

  9. Defining the functions of public health governance.

    PubMed

    Carlson, Valeria; Chilton, Marita J; Corso, Liza C; Beitsch, Leslie M

    2015-04-01

    We conducted a literature review in 2011 to determine if accepted governance functions continue to reflect the role of public health governing entities. Reviewing literature and other source documents, as well as consulting with practitioners, resulted in an iterative process that identified 6 functions of public health governance and established definitions for each of these: policy development; resource stewardship; continuous improvement; partner engagement; legal authority; and oversight of a health department. These functions provided context for the role of governing entities in public health practice and aligned well with existing public health accreditation standards. Public health systems research can build from this work in future explorations of the contributions of governance to health department performance.

  10. Considerations and Challenges in Defining Optimal Iron Utilization in Hemodialysis

    PubMed Central

    Pai, Amy Barton; Chan, Christopher T.; Coyne, Daniel W.; Hung, Adriana M.; Kovesdy, Csaba P.; Fishbane, Steven

    2015-01-01

    Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population. PMID:25542967

  11. A Neuroeconomics Approach to Inferring Utility Functions in Sensorimotor Control

    PubMed Central

    2004-01-01

    Making choices is a fundamental aspect of human life. For over a century experimental economists have characterized the decisions people make based on the concept of a utility function. This function increases with increasing desirability of the outcome, and people are assumed to make decisions so as to maximize utility. When utility depends on several variables, indifference curves arise that represent outcomes with identical utility that are therefore equally desirable. Whereas in economics utility is studied in terms of goods and services, the sensorimotor system may also have utility functions defining the desirability of various outcomes. Here, we investigate the indifference curves when subjects experience forces of varying magnitude and duration. Using a two-alternative forced-choice paradigm, in which subjects chose between different magnitude–duration profiles, we inferred the indifference curves and the utility function. Such a utility function defines, for example, whether subjects prefer to lift a 4-kg weight for 30 s or a 1-kg weight for a minute. The measured utility function depends nonlinearly on the force magnitude and duration and was remarkably conserved across subjects. This suggests that the utility function, a central concept in economics, may be applicable to the study of sensorimotor control. PMID:15383835

  12. Defining Predictive Probability Functions for Species Sampling Models

    PubMed Central

    Lee, Jaeyong; Quintana, Fernando A.; Müller, Peter; Trippa, Lorenzo

    2013-01-01

    We review the class of species sampling models (SSM). In particular, we investigate the relation between the exchangeable partition probability function (EPPF) and the predictive probability function (PPF). It is straightforward to define a PPF from an EPPF, but the converse is not necessarily true. In this paper we introduce the notion of putative PPFs and show novel conditions for a putative PPF to define an EPPF. We show that all possible PPFs in a certain class have to define (unnormalized) probabilities for cluster membership that are linear in cluster size. We give a new necessary and sufficient condition for arbitrary putative PPFs to define an EPPF. Finally, we show posterior inference for a large class of SSMs with a PPF that is not linear in cluster size and discuss a numerical method to derive its PPF. PMID:24368874

  13. Defining mental disorder. Exploring the 'natural function' approach

    PubMed Central

    2011-01-01

    Due to several socio-political factors, to many psychiatrists only a strictly objective definition of mental disorder, free of value components, seems really acceptable. In this paper, I will explore a variant of such an objectivist approach to defining metal disorder, natural function objectivism. Proponents of this approach make recourse to the notion of natural function in order to reach a value-free definition of mental disorder. The exploration of Christopher Boorse's 'biostatistical' account of natural function (1) will be followed an investigation of the 'hybrid naturalism' approach to natural functions by Jerome Wakefield (2). In the third part, I will explore two proposals that call into question the whole attempt to define mental disorder (3). I will conclude that while 'natural function objectivism' accounts fail to provide the backdrop for a reliable definition of mental disorder, there is no compelling reason to conclude that a definition cannot be achieved. PMID:21255405

  14. Defining and Assessing Public Health Functions: A Global Analysis.

    PubMed

    Martin-Moreno, Jose M; Harris, Meggan; Jakubowski, Elke; Kluge, Hans

    2016-01-01

    Given the broad scope and intersectoral nature of public health structures and practices, there are inherent difficulties in defining which services fall under the public health remit and in assessing their capacity and performance. The aim of this study is to analyze how public health functions and practice have been defined and operationalized in different countries and regions around the world, with a specific focus on assessment tools that have been developed to evaluate the performance of essential public health functions, services, and operations. Our review has identified nearly 100 countries that have carried out assessments, using diverse analytical and methodological approaches. The assessment processes have evolved quite differently according to administrative arrangements and resource availability, but some key contextual factors emerge that seem to favor policy-oriented follow-up. These include local ownership of the assessment process, policymakers' commitment to reform, and expert technical advice for implementation. PMID:26789385

  15. How should spin-weighted spherical functions be defined?

    NASA Astrophysics Data System (ADS)

    Boyle, Michael

    2016-09-01

    Spin-weighted spherical functions provide a useful tool for analyzing tensor-valued functions on the sphere. A tensor field can be decomposed into complex-valued functions by taking contractions with tangent vectors on the sphere and the normal to the sphere. These component functions are usually presented as functions on the sphere itself, but this requires an implicit choice of distinguished tangent vectors with which to contract. Thus, we may more accurately say that spin-weighted spherical functions are functions of both a point on the sphere and a choice of frame in the tangent space at that point. The distinction becomes extremely important when transforming the coordinates in which these functions are expressed, because the implicit choice of frame will also transform. Here, it is proposed that spin-weighted spherical functions should be treated as functions on the spin or rotation groups, which simultaneously tracks the point on the sphere and the choice of tangent frame by rotating elements of an orthonormal basis. In practice, the functions simply take a quaternion argument and produce a complex value. This approach more cleanly reflects the geometry involved, and allows for a more elegant description of the behavior of spin-weighted functions. In this form, the spin-weighted spherical harmonics have simple expressions as elements of the Wigner 𝔇 representations, and transformations under rotation are simple. Two variants of the angular-momentum operator are defined directly in terms of the spin group; one is the standard angular-momentum operator L, while the other is shown to be related to the spin-raising operator ð.

  16. Utility functions predict variance and skewness risk preferences in monkeys.

    PubMed

    Genest, Wilfried; Stauffer, William R; Schultz, Wolfram

    2016-07-26

    Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals' preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals' preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys' choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences. PMID:27402743

  17. Utility functions predict variance and skewness risk preferences in monkeys

    PubMed Central

    Genest, Wilfried; Stauffer, William R.; Schultz, Wolfram

    2016-01-01

    Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals’ preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals’ preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys’ choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences. PMID:27402743

  18. Utility functions predict variance and skewness risk preferences in monkeys.

    PubMed

    Genest, Wilfried; Stauffer, William R; Schultz, Wolfram

    2016-07-26

    Utility is the fundamental variable thought to underlie economic choices. In particular, utility functions are believed to reflect preferences toward risk, a key decision variable in many real-life situations. To assess the validity of utility representations, it is therefore important to examine risk preferences. In turn, this approach requires formal definitions of risk. A standard approach is to focus on the variance of reward distributions (variance-risk). In this study, we also examined a form of risk related to the skewness of reward distributions (skewness-risk). Thus, we tested the extent to which empirically derived utility functions predicted preferences for variance-risk and skewness-risk in macaques. The expected utilities calculated for various symmetrical and skewed gambles served to define formally the direction of stochastic dominance between gambles. In direct choices, the animals' preferences followed both second-order (variance) and third-order (skewness) stochastic dominance. Specifically, for gambles with different variance but identical expected values (EVs), the monkeys preferred high-variance gambles at low EVs and low-variance gambles at high EVs; in gambles with different skewness but identical EVs and variances, the animals preferred positively over symmetrical and negatively skewed gambles in a strongly transitive fashion. Thus, the utility functions predicted the animals' preferences for variance-risk and skewness-risk. Using these well-defined forms of risk, this study shows that monkeys' choices conform to the internal reward valuations suggested by their utility functions. This result implies a representation of utility in monkeys that accounts for both variance-risk and skewness-risk preferences.

  19. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia

    PubMed Central

    Klco, Jeffery M.; Spencer, David H.; Miller, Christopher A.; Griffith, Malachi; Lamprecht, Tamara L.; O’Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Fulton, Robert S.; Eades, William C.; Link, Daniel C.; Graubert, Timothy A.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Wilson, Richard K.; Ley, Timothy J.

    2014-01-01

    Summary The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by whole genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically-defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients. PMID:24613412

  20. The utility and validity of current diagnostic procedures for defining temporomandibular disorder patients.

    PubMed

    Clark, G T; Delcanho, R E; Goulet, J P

    1993-08-01

    This paper describes the evolution of different concepts of classifying and defining Temporomandibular Disorders (TMD) for both clinical and research settings. The literature is reviewed with respect to the utility and validity of the different questionnaire and examination procedures that have been used to assess TMD patients. The presented view is that many of these procedures have not been validated, that there is a lack of standardization in the use of the procedures themselves, and that an ideal method of classifying this broad group of patients into better-defined subgroups has not yet been developed. More standardized and better-defined research by trained and calibrated researchers is needed worldwide to elucidate these subgroups so that a better and widely agreed upon research classification system can be developed for widespread use. It also seems clear that as research requirements for defining TMD patient subgroups become more stringent over time, it may not be practical for the clinician to implement them on a day-to-day basis in his or her practice. As such, a practical utilitarian definition of the common subtype of TMD patients is also needed which parallels any research grouping, so that data from research are valuable and generalizable to the practicing clinician.

  1. Subnetwork State Functions Define Dysregulated Subnetworks in Cancer

    NASA Astrophysics Data System (ADS)

    Chowdhury, Salim A.; Nibbe, Rod K.; Chance, Mark R.; Koyutürk, Mehmet

    Emerging research demonstrates the potential of protein-protein interaction (PPI) networks in uncovering the mechanistic bases of cancers, through identification of interacting proteins that are coordinately dysregulated in tumorigenic and metastatic samples. When used as features for classification, such coordinately dysregulated subnetworks improve diagnosis and prognosis of cancer considerably over single-gene markers. However, existing methods formulate coordination between multiple genes through additive representation of their expression profiles and utilize greedy heuristics to identify dysregulated subnetworks, which may not be well suited to the potentially combinatorial nature of coordinate dysregulation. Here, we propose a combinatorial formulation of coordinate dysregulation and decompose the resulting objective function to cast the problem as one of identifying subnetwork state functions that are indicative of phenotype. Based on this formulation, we show that coordinate dysregulation of larger subnetworks can be bounded using simple statistics on smaller subnetworks. We then use these bounds to devise an efficient algorithm, Crane, that can search the subnetwork space more effectively than simple greedy algorithms. Comprehensive cross-classification experiments show that subnetworks identified by Crane significantly outperform those identified by greedy algorithms in predicting metastasis of colorectal cancer (CRC).

  2. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

    PubMed Central

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    Objectives The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration.

  3. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients

    PubMed Central

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    Objectives The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. Patients and methods During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration. PMID:27621614

  4. Role of motor unit structure in defining function

    NASA Technical Reports Server (NTRS)

    Monti, R. J.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

  5. Pyranopterin conformation defines the function of molybdenum and tungsten enzymes.

    PubMed

    Rothery, Richard A; Stein, Benjamin; Solomonson, Matthew; Kirk, Martin L; Weiner, Joel H

    2012-09-11

    We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.

  6. Utility of cheiloscopy, rugoscopy, and dactyloscopy for human identification in a defined cohort

    PubMed Central

    Mutalik, Vimi S.; Menon, Aparna; Jayalakshmi, N.; Kamath, Asha; Raghu, A. R.

    2013-01-01

    Background: Identification is of paramount importance in any forensic investigation. Positive identification of living or deceased using distinctive traits is a cornerstone of forensic science. The uniqueness of these patterns and subtle distinction between traits has offered worthy supplemental tools in establishing the true nature of facts. Aim: The first aim of our study was to determine the most common pattern of lip prints, palatal rugae, and finger prints in the study subjects. Secondly, to determine if any specific pattern of lip print, palatal rugae, or the finger print concurs in individuals, and thereby establish a database of these prototypes for human identification from a defined cohort. Materials and Methods: The sample size comprised 100 female students of a dental college staying together in the hostel. Lip prints were recorded on a white bond sheet using lipstick, palatal rugae on dental casts, and finger prints using printer's blue ink. Results: Our observation suggested that the reticular pattern of lip print, the wavy pattern of palatal rugae, and the loop pattern of finger prints were the predominant patterns. Correlation of the three parameters did not reveal significant differences. Conclusions: This approach of human identification utilizing conventional techniques and relevant parameters is pertinent in defined groups. However, larger representative sample with robust analytical tools may provide a necessary blueprint of human identification. PMID:23960407

  7. Reconciling resource utilization and resource selection functions

    USGS Publications Warehouse

    Hooten, Mevin B.; Hanks, Ephraim M.; Johnson, Devin S.; Alldredge, Mat W.

    2013-01-01

    Summary: 1. Analyses based on utilization distributions (UDs) have been ubiquitous in animal space use studies, largely because they are computationally straightforward and relatively easy to employ. Conventional applications of resource utilization functions (RUFs) suggest that estimates of UDs can be used as response variables in a regression involving spatial covariates of interest. 2. It has been claimed that contemporary implementations of RUFs can yield inference about resource selection, although to our knowledge, an explicit connection has not been described. 3. We explore the relationships between RUFs and resource selection functions from a hueristic and simulation perspective. We investigate several sources of potential bias in the estimation of resource selection coefficients using RUFs (e.g. the spatial covariance modelling that is often used in RUF analyses). 4. Our findings illustrate that RUFs can, in fact, serve as approximations to RSFs and are capable of providing inference about resource selection, but only with some modification and under specific circumstances. 5. Using real telemetry data as an example, we provide guidance on which methods for estimating resource selection may be more appropriate and in which situations. In general, if telemetry data are assumed to arise as a point process, then RSF methods may be preferable to RUFs; however, modified RUFs may provide less biased parameter estimates when the data are subject to location error.

  8. Reconciling resource utilization and resource selection functions.

    PubMed

    Hooten, Mevin B; Hanks, Ephraim M; Johnson, Devin S; Alldredge, Mat W

    2013-11-01

    1. Analyses based on utilization distributions (UDs) have been ubiquitous in animal space use studies, largely because they are computationally straightforward and relatively easy to employ. Conventional applications of resource utilization functions (RUFs) suggest that estimates of UDs can be used as response variables in a regression involving spatial covariates of interest. 2. It has been claimed that contemporary implementations of RUFs can yield inference about resource selection, although to our knowledge, an explicit connection has not been described. 3. We explore the relationships between RUFs and resource selection functions from a hueristic and simulation perspective. We investigate several sources of potential bias in the estimation of resource selection coefficients using RUFs (e.g. the spatial covariance modelling that is often used in RUF analyses). 4. Our findings illustrate that RUFs can, in fact, serve as approximations to RSFs and are capable of providing inference about resource selection, but only with some modification and under specific circumstances. 5. Using real telemetry data as an example, we provide guidance on which methods for estimating resource selection may be more appropriate and in which situations. In general, if telemetry data are assumed to arise as a point process, then RSF methods may be preferable to RUFs; however, modified RUFs may provide less biased parameter estimates when the data are subject to location error.

  9. Defining and Applying a Functionality Approach to Intellectual Disability

    ERIC Educational Resources Information Center

    Luckasson, R.; Schalock, R. L.

    2013-01-01

    Background: The current functional models of disability do not adequately incorporate significant changes of the last three decades in our understanding of human functioning, and how the human functioning construct can be applied to clinical functions, professional practices and outcomes evaluation. Methods: The authors synthesise current…

  10. Flexible associations between Pocillopora corals and Symbiodinium limit utility of symbiosis ecology in defining species

    NASA Astrophysics Data System (ADS)

    Cunning, R.; Glynn, P. W.; Baker, A. C.

    2013-09-01

    Corals in the genus Pocillopora are the primary framework builders of eastern tropical Pacific (ETP) reefs. These corals typically associate with algal symbionts (genus Symbiodinium) in clade C and/or D, with clade D associations having greater thermal tolerance and resistance to bleaching. Recently, cryptic "species" delineations within both Pocillopora and Symbiodinium have been suggested, with host-symbiont specificity used as a supporting taxonomic character in both genera. In particular, it has been suggested that three lineages of Pocillopora (types 1-3) exist in the ETP, of which type 1 is the exclusive host of heat-tolerant Symbiodinium D1. This host specificity has been used to support the species name " Symbiodinium glynni" for this symbiont. To validate these host-symbiont relationships and their taxonomic utility, we identified Pocillopora types and their associated Symbiodinium at three sites in the ETP. We found greater flexibility in host-symbiont combinations than previously reported, with both Pocillopora types 1 and 3 able to host and be dominated by Symbiodinium in clade C or D. The prevalence of certain combinations did vary among sites, showing that a gradient of specificity exists which may be mediated by evolutionary relationships and environmental disturbance history. However, these results limit the utility of apparent host-symbiont specificity (which may have been a result of undersampling) in defining species boundaries in either corals or Symbiodinium. They also suggest that a greater diversity of corals may benefit from the thermal tolerance of clade D symbionts, affirming the need to conserve Pocillopora across its entire geographic and environmental range.

  11. Defining the functional states of Th17 cells

    PubMed Central

    Lee, Youjin; Kuchroo, Vijay

    2015-01-01

    The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 Th cells into subsets but also influence the identity, plasticity and effector function of a T cell. Of the subsets, Th17 cells, named for producing interleukin 17 (IL-17) as their signature cytokine, secrete a cohort of other cytokines, including IL-22, IL-21, IL-10, IL-9, IFNγ, and GM-CSF.  In recent years, Th17 cells have emerged as key players in host defense against both extracellular pathogens and fungal infections, but they have also been implicated as one of the main drivers in the pathogenesis of autoimmunity, likely mediated in part by the cytokines that they produce. Advances in high throughput genomic sequencing have revealed unexpected heterogeneity in Th17 cells and, as a consequence, may have tremendous impact on our understanding of their functional diversity. The assortment in gene expression may also identify different functional states of Th17 cells. This review aims to understand the interplay between the cytokine regulators that drive Th17 cell differentiation and functional states in Th17 cells. PMID:27006754

  12. Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?

    PubMed

    Abdala, Ana Paula; Paton, Julian F R; Smith, Jeffrey C

    2015-07-15

    Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.

  13. Anatomical form defines color: function, form, and aesthetics.

    PubMed

    Terry, Douglas A; Geller, Willi; Tric, Olivier; Anderson, Mark J; Tourville, Monte; Kobashigawa, Alvin

    2002-01-01

    Contemporary composite materials enable the reproduction of polychromatic effects within a tooth. A broader definition of color that incorporates the anatomy and optical properties of a tooth must be developed so the dental professional can better understand the infinite possibilities of color that exist within the tooth and restoration. This article describes a direct protocol for the development of natural restorations in the posterior dentition through the integration of function, form, and color.

  14. Conditions required for citrate utilization during growth of Lactobacillus casei ATCC334 in chemically defined medium and cheddar cheese extract.

    PubMed

    Díaz-Muñiz, Ilenys; Steele, James L

    2006-10-01

    Conditions required for citrate utilization by Lactobacillus casei ATCC334 were identified. Citrate was utilized by this microorganism in modified Chemically Defined Media (mCDM) as an energy source, solely in the presence of limiting concentrations of galactose. The presence of glucose inhibited citrate utilization by this microorganism even when added in limiting concentrations. Utilization of citrate occurred at pH 6.0 +/- 0.2 and 5.1 +/- 0.2. Together these observations suggest that citrate is an energy source for L. casei in ripening cheese only when the residual levels of carbohydrate post-fermentation are limiting (<2.5 mM), and lactose or glucose are absent. However, citrate utilization by this organism was observed in Cheddar cheese extract (CCE), which naturally contains both lactose and galactose, at the beginning of late-logarithmic phase and regardless of the galactose concentration present in the media.

  15. Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes.

    PubMed

    Abdelmohsen, Loai K E A; Williams, David S; Pille, Jan; Ozel, Sema G; Rikken, Roger S M; Wilson, Daniela A; van Hest, Jan C M

    2016-08-01

    Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal "click" chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research.

  16. Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes

    PubMed Central

    2016-01-01

    Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal “click” chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research. PMID:27374777

  17. Defining a Model for Mitochondrial Function in mESC Differentiation

    EPA Science Inventory

    Defining a Model for Mitochondrial Function in mESC DifferentiationDefining a Model for Mitochondrial Function in mESC Differentiation Differentiating embryonic stem cells (ESCs) undergo mitochondrial maturation leading to a switch from a system dependent upon glycolysis to a re...

  18. An Empirical Assessment of the Form of Utility Functions

    ERIC Educational Resources Information Center

    Kirby, Kris N.

    2011-01-01

    Utility functions, which relate subjective value to physical attributes of experience, are fundamental to most decision theories. Seven experiments were conducted to test predictions of the most widely assumed mathematical forms of utility (power, log, and negative exponential), and a function proposed by Rachlin (1992). For pairs of gambles for…

  19. On a New Class of p-Valent Meromorphic Functions Defined in Conic Domains

    PubMed Central

    Alamri, Mohammed Ali

    2016-01-01

    We define a new class of multivalent meromorphic functions using the generalised hypergeometric function. We derived this class related to conic domain. It is also shown that this new class of functions, under certain conditions, becomes a class of starlike functions. Some results on inclusion and closure properties are also derived. PMID:27529076

  20. On a New Class of p-Valent Meromorphic Functions Defined in Conic Domains.

    PubMed

    Alamri, Mohammed Ali; Darus, Maslina

    2016-01-01

    We define a new class of multivalent meromorphic functions using the generalised hypergeometric function. We derived this class related to conic domain. It is also shown that this new class of functions, under certain conditions, becomes a class of starlike functions. Some results on inclusion and closure properties are also derived. PMID:27529076

  1. Fabrication of a normally-closed microvalve utilizing lithographically defined silicone micro O-rings

    NASA Astrophysics Data System (ADS)

    Lemke, T.; Kloeker, J.; Biancuzzi, G.; Huesgen, T.; Goldschmidtboeing, F.; Woias, P.

    2011-02-01

    The focus of this work is on the development of a simple and variable process chain for the integration of flexible silicone material into silicon-based microfluidic devices. A normally-closed microvalve is chosen as a demonstrator device, as it combines features that are not easily obtained from silicon devices alone, especially, a high leak tightness of up to 1 bar pressure difference in the closed state and a high forward flow of several mL min^{-1} in the open state. For this purpose, a photopatternable silicone is used as a deformable circular valve lip between a piezoelectrically actuated membrane and a valve seat, similar to a micro O-ring with a width of 50 µm. The microvalve is piezo actuated by monolayer piezo actuators with a peak-to-peak driving voltage of V_{p{--p}} = 200 V. The micro O-ring is pre-deformed by 2.8 µm during the valve fabrication process to yield the normally-closed behavior. A dry film resist lamination technology is developed for this critical process step to mate the two silicon wafers with the actuation membrane, the valve seat and the silicone O-ring in between at a well-defined distance. The dry film resist is used in a multifunctional way, not only to pre-deform the valve lip, but also to define the geometry of the valve chamber and to ensure a leak-tight connection of both wafers. Altogether, a peak value for the on- to off-ratio of the normally-closed microvalve higher than 30 000 is measured. This opens a wide range of potential applications, e.g. in micro-dosing, drug delivery, μ-TAS and microfluidics for biological or chemical applications in general.

  2. Utilization of a mini-mu transposon to construct defined mutants in Streptococcus mutans.

    PubMed

    Kuramitsu, H K

    1987-09-01

    The gtfB gene coding for glucosyltransferase-I (GTF-I) activity previously isolated from Streptococcus mutans GS-5 was insertionally inactivated with the newly constructed transposon MudE in an Escherichia coli background. Insertion of MudE into various regions of the gtfB gene led to inactivation of GTF-I activity. The altered gene was introduced back into S. mutans GS-5 by transformation and produced mutants defective in insoluble glucan synthesis as well as the ability to colonize smooth surfaces in the presence of sucrose. Therefore, the MudE transposon can be utilized to produce specific mutants in oral streptococci as well as in other transformable Gram-positive bacteria expressing an erythromycin-resistance marker.

  3. When we should say no to TAVR-Defining the line between utility and futility.

    PubMed

    Khan, Zubair A; Aji, Janah; Soomro, Armaghan; Malik, Sara; Saeed, Wajeeha; Sardar, M Rizwan

    2016-09-01

    History of prior coronary artery bypass surgery (CABG) is a frequent scenario encountered in patients with severe symptomatic aortic stenosis deemed inoperable and referred for transcatheter aortic valve replacement (TAVR). Aside from indices of frailty and other comorbidities, these patients remain at higher risk for peri-operative mortality and morbidity compared to their counterparts without prior CABG. Presence of concomitant peripheral arterial disease and patent left internal mammary artery (LIMA) graft pose further access related challenges. We present a case of an 84-year-old female with prior CABG and severe PAD who underwent transapical TAVR for severe symptomatic AS sustaining an acute myocardial injury from damage to her apical epicardial collateral circulation. The case entails the importance of recognition of epicardial coronary collateralization where a transapical approach is best avoided or further aided by utilization of peri-procedural angiographic/fluoroscopy guidance to avoid epicardial vascular injury.

  4. Differential Item Functioning Detection across Two Methods of Defining Group Comparisons: Pairwise and Composite Group Comparisons

    ERIC Educational Resources Information Center

    Sari, Halil Ibrahim; Huggins, Anne Corinne

    2015-01-01

    This study compares two methods of defining groups for the detection of differential item functioning (DIF): (a) pairwise comparisons and (b) composite group comparisons. We aim to emphasize and empirically support the notion that the choice of pairwise versus composite group definitions in DIF is a reflection of how one defines fairness in DIF…

  5. Functions of Conflict: Perceived Utility in the Emergent Professions.

    ERIC Educational Resources Information Center

    Henkin, Alan B.; And Others

    1991-01-01

    Describes perceptions of conflict as a utility (functional conflict) among 1,953 department executives in programs of social work, education, and nursing (the emergent professions); and analyzes perceptual data in terms of organizational conflict climate and demographics. Variations in terms of perceived operational utility of organizational…

  6. Optimal Wonderful Life Utility Functions in Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Wolpert, David H.; Tumer, Kagan; Swanson, Keith (Technical Monitor)

    2000-01-01

    The mathematics of Collective Intelligence (COINs) is concerned with the design of multi-agent systems so as to optimize an overall global utility function when those systems lack centralized communication and control. Typically in COINs each agent runs a distinct Reinforcement Learning (RL) algorithm, so that much of the design problem reduces to how best to initialize/update each agent's private utility function, as far as the ensuing value of the global utility is concerned. Traditional team game solutions to this problem assign to each agent the global utility as its private utility function. In previous work we used the COIN framework to derive the alternative Wonderful Life Utility (WLU), and experimentally established that having the agents use it induces global utility performance up to orders of magnitude superior to that induced by use of the team game utility. The WLU has a free parameter (the clamping parameter) which we simply set to zero in that previous work. Here we derive the optimal value of the clamping parameter, and demonstrate experimentally that using that optimal value can result in significantly improved performance over that of clamping to zero, over and above the improvement beyond traditional approaches.

  7. The evolution of utility functions and psychological altruism.

    PubMed

    Clavien, Christine; Chapuisat, Michel

    2016-04-01

    Numerous studies show that humans tend to be more cooperative than expected given the assumption that they are rational maximizers of personal gain. As a result, theoreticians have proposed elaborated formal representations of human decision-making, in which utility functions including "altruistic" or "moral" preferences replace the purely self-oriented "Homo economicus" function. Here we review mathematical approaches that provide insights into the mathematical stability of alternative utility functions. Candidate utility functions may be evaluated with help of game theory, classical modeling of social evolution that focuses on behavioral strategies, and modeling of social evolution that focuses directly on utility functions. We present the advantages of the latter form of investigation and discuss one surprisingly precise result: "Homo economicus" as well as "altruistic" utility functions are less stable than a function containing a preference for the common welfare that is only expressed in social contexts composed of individuals with similar preferences. We discuss the contribution of mathematical models to our understanding of human other-oriented behavior, with a focus on the classical debate over psychological altruism. We conclude that human can be psychologically altruistic, but that psychological altruism evolved because it was generally expressed towards individuals that contributed to the actor's fitness, such as own children, romantic partners and long term reciprocators. PMID:26598465

  8. The evolution of utility functions and psychological altruism.

    PubMed

    Clavien, Christine; Chapuisat, Michel

    2016-04-01

    Numerous studies show that humans tend to be more cooperative than expected given the assumption that they are rational maximizers of personal gain. As a result, theoreticians have proposed elaborated formal representations of human decision-making, in which utility functions including "altruistic" or "moral" preferences replace the purely self-oriented "Homo economicus" function. Here we review mathematical approaches that provide insights into the mathematical stability of alternative utility functions. Candidate utility functions may be evaluated with help of game theory, classical modeling of social evolution that focuses on behavioral strategies, and modeling of social evolution that focuses directly on utility functions. We present the advantages of the latter form of investigation and discuss one surprisingly precise result: "Homo economicus" as well as "altruistic" utility functions are less stable than a function containing a preference for the common welfare that is only expressed in social contexts composed of individuals with similar preferences. We discuss the contribution of mathematical models to our understanding of human other-oriented behavior, with a focus on the classical debate over psychological altruism. We conclude that human can be psychologically altruistic, but that psychological altruism evolved because it was generally expressed towards individuals that contributed to the actor's fitness, such as own children, romantic partners and long term reciprocators.

  9. Use of morphological characteristics to define functional groups of predatory fishes in the Celtic Sea.

    PubMed

    Reecht, Y; Rochet, M-J; Trenkel, V M; Jennings, S; Pinnegar, J K

    2013-08-01

    An ecomorphological method was developed, with a focus on predation functions, to define functional groups in the Celtic Sea fish community. Eleven functional traits, measured for 930 individuals from 33 species, led to 11 functional groups. Membership of functional groups was linked to body size and taxonomy. For seven species, there were ontogenetic changes in group membership. When diet composition, expressed as the proportions of different prey types recorded in stomachs, was compared among functional groups, morphology-based predictions accounted for 28-56% of the interindividual variance in prey type. This was larger than the 12-24% of variance that could be explained solely on the basis of body size.

  10. Subordination properties for certain subclasses of analytic functions defined by a general differential operator

    NASA Astrophysics Data System (ADS)

    Deniz, Erhan; Özkan, Yücel

    2016-04-01

    Recently, Deniz and Özkan [2] introduced two new subclasses T Sm*(α,λ) and TCm (α, λ) of analytic functions which are defined by means of a new general differantial operatör. In this paper, subordinate results related these subclasses are obtained.

  11. Assessing the Utility of a Demand Assessment for Functional Analysis

    ERIC Educational Resources Information Center

    Roscoe, Eileen M.; Rooker, Griffin W.; Pence, Sacha T.; Longworth, Lynlea J.

    2009-01-01

    We evaluated the utility of an assessment for identifying tasks for the functional analysis demand condition with 4 individuals who had been diagnosed with autism. During the demand assessment, a therapist presented a variety of tasks, and observers measured problem behavior and compliance to identify demands associated with low levels of…

  12. Functional and Software Considerations for Bibliographic Data Base Utilization.

    ERIC Educational Resources Information Center

    Cadwallader, Gouverneur

    This is the fourth in a series of eight reports of a research study for the National Agricultural Library (NAL) on the effective utilization of bibliographic data bases in machine-readable form. It describes the general functional and software requirements of an NAL system using external sources of bibliographic data. Various system design…

  13. Illustrating Consumer Theory with the CES Utility Function

    ERIC Educational Resources Information Center

    Tohamy, Soumaya M.; Mixon, J. Wilson, Jr.

    2004-01-01

    The authors use Microsoft Excel to derive compensated and uncompensated demand curves. They use a constant elasticity of substitution (CES) utility function to show how changes in a good's price or income affect the quantities demanded of that good and of the other composite good, using Excel's Solver. They provide three contributions. First, they…

  14. A novel utility function for energy-efficient power control game in cognitive radio networks.

    PubMed

    Al-Gumaei, Yousef Ali; Noordin, Kamarul Ariffin; Reza, Ahmed Wasif; Dimyati, Kaharudin

    2015-01-01

    Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence. PMID:26258522

  15. A Novel Utility Function for Energy-Efficient Power Control Game in Cognitive Radio Networks

    PubMed Central

    Al-Gumaei, Yousef Ali; Noordin, Kamarul Ariffin; Reza, Ahmed Wasif; Dimyati, Kaharudin

    2015-01-01

    Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence. PMID:26258522

  16. A novel utility function for energy-efficient power control game in cognitive radio networks.

    PubMed

    Al-Gumaei, Yousef Ali; Noordin, Kamarul Ariffin; Reza, Ahmed Wasif; Dimyati, Kaharudin

    2015-01-01

    Spectrum scarcity is a major challenge in wireless communications systems requiring efficient usage and utilization. Cognitive radio network (CRN) is found as a promising technique to solve this problem of spectrum scarcity. It allows licensed and unlicensed users to share the same licensed spectrum band. Interference resulting from cognitive radios (CRs) has undesirable effects on quality of service (QoS) of both licensed and unlicensed systems where it causes degradation in received signal-to-noise ratio (SIR) of users. Power control is one of the most important techniques that can be used to mitigate interference and guarantee QoS in both systems. In this paper, we develop a new approach of a distributed power control for CRN based on utility and pricing. QoS of CR user is presented as a utility function via pricing and a distributed power control as a non-cooperative game in which users maximize their net utility (utility-price). We define the price as a real function of transmit power to increase pricing charge of the farthest CR users. We prove that the power control game proposed in this study has Nash Equilibrium as well as it is unique. The obtained results show that the proposed power control algorithm based on a new utility function has a significant reduction in transmit power consumption and high improvement in speed of convergence.

  17. Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency

    PubMed Central

    Kim, Young Eun; Kim, Yu-na; Kim, Jung A.; Kim, Ho Min; Jung, Yongwon

    2015-01-01

    Supramolecular protein assemblies offer novel nanoscale architectures with molecular precision and unparalleled functional diversity. A key challenge, however, is to create precise nano-assemblies of functional proteins with both defined structures and a controlled number of protein-building blocks. Here we report a series of supramolecular green fluorescent protein oligomers that are assembled in precise polygonal geometries and prepared in a monodisperse population. Green fluorescent protein is engineered to be self-assembled in cells into oligomeric assemblies that are natively separated in a single-protein resolution by surface charge manipulation, affording monodisperse protein (nano)polygons from dimer to decamer. Several functional proteins are multivalently displayed on the oligomers with controlled orientations. Spatial arrangements of protein oligomers and displayed functional proteins are directly visualized by a transmission electron microscope. By employing our functional protein assemblies, we provide experimental insight into multivalent protein–protein interactions and tools to manipulate receptor clustering on live cell surfaces. PMID:25972078

  18. Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency

    NASA Astrophysics Data System (ADS)

    Kim, Young Eun; Kim, Yu-Na; Kim, Jung A.; Kim, Ho Min; Jung, Yongwon

    2015-05-01

    Supramolecular protein assemblies offer novel nanoscale architectures with molecular precision and unparalleled functional diversity. A key challenge, however, is to create precise nano-assemblies of functional proteins with both defined structures and a controlled number of protein-building blocks. Here we report a series of supramolecular green fluorescent protein oligomers that are assembled in precise polygonal geometries and prepared in a monodisperse population. Green fluorescent protein is engineered to be self-assembled in cells into oligomeric assemblies that are natively separated in a single-protein resolution by surface charge manipulation, affording monodisperse protein (nano)polygons from dimer to decamer. Several functional proteins are multivalently displayed on the oligomers with controlled orientations. Spatial arrangements of protein oligomers and displayed functional proteins are directly visualized by a transmission electron microscope. By employing our functional protein assemblies, we provide experimental insight into multivalent protein-protein interactions and tools to manipulate receptor clustering on live cell surfaces.

  19. National Survey of Geriatricians to Define Functional Decline in Elderly People with Minor Trauma

    PubMed Central

    Abdulaziz, Kasim; Perry, Jeffrey J.; Taljaard, Monica; Émond, Marcel; Lee, Jacques S.; Wilding, Laura; Sirois, Marie-Josée; Brehaut, Jamie

    2016-01-01

    Background This study was designed to determine a clinically significant point drop in function to define functional decline and the required sensitivity for a clinical decision tool to identify elderly patients at high risk of functional decline following a minor injury. Methods After a rigorous development process, a survey questionnaire was administered to a random sample of 178 geriatricians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique. Results We obtained a satisfactory response rate of 70.5%. Ninety percent of the geriatricians required a sensitivity of 90% or less for a clinical decision tool to identify injured seniors at high risk of functional decline 6 months post injury. Our results indicate that 90% of the respondents considered a drop in function of at least 2 points in activities of daily living (ADL) as clinically significant when considering all 14 ADL items. Considering only the 7 basic ADL items, 90% of physicians considered a 1 point drop as clinically significant. Conclusions A tool with a sensitivity of 90% to detect patients at risk of functional decline at 6 months post minor injury would meet or exceed the sensitivity required by 90% of geriatric specialists. These findings clearly define what is a clinically significant decline following a “minor injury.” PMID:27076859

  20. Wetting properties of model interphases coated with defined organic functional groups

    NASA Astrophysics Data System (ADS)

    Woche, Susanne K.; Goebel, Marc-O.; Guggenberger, Georg; Tunega, Daniel; Bachmann, Joerg

    2013-04-01

    Surface properties of soil particles are of particular interest regarding transport of water and sorption of solutes, especially hazardous xenobiotic species. Wetting properties (e.g. determined by contact angle, CA), governed by the functional groups exposed, are crucial to understand sorption processes in water repellent soils as well as for the geometry of water films sustaining microbial processes on the pore scale. Natural soil particle surfaces are characterized by a wide variety of mineralogical and chemical compounds. Their composition is almost impossible to identify in full. Hence, in order to get a better understanding about surface properties, an option is the usage of defined model surfaces, whereas the created surface should be comparable to natural soil interphases. We exposed smooth glass surfaces to different silane compounds, resulting in a coating covalently bound to the surface and exhibiting defined organic functional groups towards the pore space. The wetting properties as evaluated by CA and the surface free energy (SFE), calculated according to the Acid-Base Theory, were found to be a function of the specific functional group. Specifically, the treated surfaces showed a large variation of CA and SFE as function of chain length and polarity of the organic functional group. The study of wetting properties was accompanied by XPS analysis for selective detection of chemical compounds of the interphase. As the reaction mechanism of the coating process is known, the resulting interphase structure can be modeled based on energetic considerations. A next step is to use same coatings for the defined modification of the pore surfaces of porous media to study transport and sorption processes in complex three phase systems.

  1. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  2. Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

    PubMed Central

    Yu, Kelly J.; Hsu, Wan-Lun; Pfeiffer, Ruth M.; Chiang, Chun-Ju; Wang, Cheng-Ping; Lou, Pei-Jen; Cheng, Yu-Juen; Gravitt, Patti; Diehl, Scott R.; Goldstein, Alisa M.; Chen, Chien-Jen; Hildesheim, Allan

    2012-01-01

    Purpose Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated. Results A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. PMID:21447725

  3. Functional assays to define agonists and antagonists of the sigma-2 receptor

    PubMed Central

    Zeng, Chenbo; Rothfuss, Justin M.; Zhang, Jun; Vangveravong, Suwanna; Chu, Wenhua; Li, Shihong; Tu, Zhude; Xu, Jinbin; Mach, Robert H.

    2014-01-01

    The sigma-2 receptor has been identified as a biomarker in proliferating tumors. Up to date there is no well-established functional assay for defining sigma-2 agonists and antagonists. Many sigma-2 ligands with diverse structures have been shown to induce cell death in a variety of cancer cells by triggering caspase-dependent and independent apoptosis. Therefore, in the current study, we used the cell viability assay and the caspase-3 activity assay to determine sigma-2 agonists and antagonists. Three classes of sigma-2 ligands developed in our laboratory were evaluated for their potency to induce cell death in two tumor cell lines, mouse breast cancer cell line EMT-6 and human melanoma cell line MDA-MB-435. The data showed that the EC50 values of the sigma-2 ligands using the cell viability assay ranged from 11.4 μM to >200 μM, which were comparable with the EC50 values obtained using the caspase-3 assay. Based on the cytotoxicity of a sigma-2 ligand relative to that of siramesine, a commonly accepted sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists. The establishment of functional assays for defining sigma-2 agonists and antagonists will facilitate functional characterization of sigma-2 receptor ligands and sigma-2 receptors. PMID:24333652

  4. Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline

    PubMed Central

    Hochstetler, Helen; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Henley, David B.; Degenhardt, Elisabeth; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G.

    2015-01-01

    Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class. PMID:26639960

  5. Plane-wave superpositions defined by orthonormal scalar functions on two- and three-dimensional manifolds

    PubMed

    Borzdov

    2000-04-01

    Vector plane-wave superpositions defined by a given set of orthonormal scalar functions on a two- or three-dimensional manifold-beam manifold-are treated. We present a technique for composing orthonormal beams and some other specific types of fields such as three-dimensional standing waves, moving and evolving whirls. It can be used for any linear fields, in particular, electromagnetic fields in complex media and elastic fields in crystals. For electromagnetic waves in an isotropic medium or free space, unique families of exact solutions of Maxwell's equations are obtained. The solutions are illustrated by calculating fields, energy densities, and energy fluxes of beams defined by the spherical harmonics. It is shown that the obtained results can be used for a transition from the plane-wave approximation to more accurate models of real incident beams in free-space techniques for characterizing complex media. A mathematical formalism convenient for the treatment of various beams defined by the spherical harmonics is presented.

  6. Generation of Functional Inhibitory Synapses Incorporating Defined Combinations of GABA(A) or Glycine Receptor Subunits

    PubMed Central

    Dixon, Christine L.; Zhang, Yan; Lynch, Joseph W.

    2015-01-01

    Fast inhibitory neurotransmission in the brain is mediated by wide range of GABAA receptor (GABAAR) and glycine receptor (GlyR) isoforms, each with different physiological and pharmacological properties. Because multiple isoforms are expressed simultaneously in most neurons, it is difficult to define the properties of individual isoforms under synaptic stimulation conditions in vivo. Although recombinant expression systems permit the expression of individual isoforms in isolation, they require exogenous agonist application which cannot mimic the dynamic neurotransmitter profile characteristic of native synapses. We describe a neuron-HEK293 cell co-culture technique for generating inhibitory synapses incorporating defined combinations of GABAAR or GlyR subunits. Primary neuronal cultures, prepared from embryonic rat cerebral cortex or spinal cord, are used to provide presynaptic GABAergic and glycinergic terminals, respectively. When the cultures are mature, HEK293 cells expressing the subunits of interest plus neuroligin 2A are plated onto the neurons, which rapidly form synapses onto HEK293 cells. Patch clamp electrophysiology is then used to analyze the physiological and pharmacological properties of the inhibitory postsynaptic currents mediated by the recombinant receptors. The method is suitable for investigating the kinetic properties or the effects of drugs on inhibitory postsynaptic currents mediated by defined GABAAR or GlyR isoforms of interest, the effects of hereditary disease mutations on the formation and function of both types of synapses, and synaptogenesis and synaptic clustering mechanisms. The entire cell preparation procedure takes 2–5 weeks. PMID:26778954

  7. Acoustical impedance defined by wave-function solutions of the reduced Webster equation.

    PubMed

    Forbes, Barbara J

    2005-07-01

    The electrical impedance was first defined by Heaviside in 1884, and the analogy of the acoustical impedance was made by Webster in 1919. However, it can be shown that Webster did not draw a full analogy with the electromagnetic potential, the potential energy per unit charge. This paper shows that the analogous "acoustical potential" the potential energy per unit displacement of fluid, corresponds to the wave function Psi of the reduced Webster equation, which is of Klein-Gordon form. The wave function is found to obey all of Dirichlet, Von Neumann, and mixed (Robins) boundary conditions, and the latter give rise to resonance phenomena that are not elucidated by Webster's analysis. It is shown that the exact Heaviside analogy yields a complete analytic account of the one-dimensional input impedance, that accounts for both plane- and dispersive-wave propagation both at the origin and throughout the duct.

  8. Neurocognitive Function in HIV-Infected Patients: Comparison of Two Methods to Define Impairment

    PubMed Central

    Arenas-Pinto, Alejandro; Winston, Alan; Stöhr, Wolfgang; Day, John; Wiggins, Rebecca; Quah, Say Pheng; Ainsworth, Jonathan; Fleck, Sue; Dunn, David; Accoroni, Alex; Paton, Nicholas I.

    2014-01-01

    Objective To compare two definitions of neurocognitive impairment (NCI) in a large clinical trial of effectively-treated HIV-infected adults at baseline. Methods Hopkins Verbal Learning test-Revised (HVLT-R), Colour Trail (CTT) and Grooved Pegboard (GPT) tests were applied exploring five cognitive domains. Raw scores were transformed into Z-scores and NCI defined as summary NPZ-5 score one standard deviation below the mean of the normative dataset (i.e. <−1SD) or Z-scores <−1SD in at least two individual domains (categorical scale). Principal component analysis (PCA) was performed to explore the contribution of individual tests to the total variance. Results Mean NPZ-5 score was −0.72 (SD 0.98) and 178/548 (32%) participants had NPZ-5 scores <−1SD. When impairment was defined as <−1SD in at least two individual tests, 283 (52%) patients were impaired. Strong correlations between the two components of the HVLT-R test (learning/recall) (r = 0.73), and the CTT and (attention/executive functioning) (r = 0.66) were observed. PCA showed a clustering with three components accounting for 88% of the total variance. When patients who scored <−1SD only in two correlated tests were considered as not impaired, prevalence of NCI was 43%. When correlated test scores were averaged, 36% of participants had NPZ-3 scores <−1SD and 32% underperformed in at least two individual tests. Conclusion Controlling for differential contribution of individual test-scores on the overall performance and the level of correlation between components of the test battery used appear to be important when testing cognitive function. These two factors are likely to affect both summary scores and categorical scales in defining cognitive impairment. Trial registration EUDRACT: 2007-006448-23 and ISRCTN04857074. PMID:25078406

  9. Dissociated phenotypes in presenilin transgenic mice define functionally distinct γ-secretases

    PubMed Central

    Mastrangelo, Peter; Mathews, Paul M.; Chishti, M. Azhar; Schmidt, Stephen D.; Gu, Yongjun; Yang, Jing; Mazzella, Matthew J.; Coomaraswamy, Janaky; Horne, Patrick; Strome, Bob; Pelly, Heather; Levesque, Georges; Ebeling, Chris; Jiang, Ying; Nixon, Ralph A.; Rozmahel, Richard; Fraser, Paul E.; George-Hyslop, Peter St; Carlson, George A.; Westaway, David

    2005-01-01

    γ-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex. This endoproteolytic activity cleaves within transmembrane domains of amyloid-β precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-β (Aβ) 40 peptide to greater production of Aβ42. Although studies in PS1/PS2-deficient embryonic cells define overlapping activities for these proteins, in vivo complementation of PS1-deficient animals described here reveals an unexpected spectrum of activities dictated by PS1 and PS2 alleles. Unlike PS1 transgenes, wild-type PS2 transgenes expressed in the mouse CNS support little Aβ40 or Aβ42 production, and FAD PS2 alleles support robust production of only Aβ42. Although wild-type PS2 transgenes failed to rescue Notch-associated skeletal defects in PS1 hypomorphs, a “gained” competence in this regard was apparent for FAD alleles of PS2. The range of discrete and divergent processing activities in mice reconstituted with different PS genes and alleles argues against γ-secretase being a single enzyme with intrinsically relaxed substrate and cleavage site specificities. Instead, our studies define functionally distinct γ-secretase variants. We speculate that extrinsic components, in combination with core complexes, may tailor functional variants of this enzyme to their preferred substrates. PMID:15951428

  10. FunTree: a resource for exploring the functional evolution of structurally defined enzyme superfamilies.

    PubMed

    Furnham, Nicholas; Sillitoe, Ian; Holliday, Gemma L; Cuff, Alison L; Rahman, Syed A; Laskowski, Roman A; Orengo, Christine A; Thornton, Janet M

    2012-01-01

    FunTree is a new resource that brings together sequence, structure, phylogenetic, chemical and mechanistic information for structurally defined enzyme superfamilies. Gathering together this range of data into a single resource allows the investigation of how novel enzyme functions have evolved within a structurally defined superfamily as well as providing a means to analyse trends across many superfamilies. This is done not only within the context of an enzyme's sequence and structure but also the relationships of their reactions. Developed in tandem with the CATH database, it currently comprises 276 superfamilies covering ~1800 (70%) of sequence assigned enzyme reactions. Central to the resource are phylogenetic trees generated from structurally informed multiple sequence alignments using both domain structural alignments supplemented with domain sequences and whole sequence alignments based on commonality of multi-domain architectures. These trees are decorated with functional annotations such as metabolite similarity as well as annotations from manually curated resources such the catalytic site atlas and MACiE for enzyme mechanisms. The resource is freely available through a web interface: www.ebi.ac.uk/thorton-srv/databases/FunTree.

  11. Utilization of Skills in the Care of the Adult with Common, Well-Defined Health Deviations II (NS 227): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Green, Elizabeth G.; Yates, Laura H.

    "Utilization of Skills in the Care of the Adult with Common, Well-Defined Health Deviations II" (NS 227) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students implement increasingly complex nursing strategies and develop new competencies related to patients with cardiovascular, respiratory,…

  12. Utilization of Skills in the Care of the Patient with Common, Well-Defined Health Deviations I (NS 217): Competency-Based Course Syllabus.

    ERIC Educational Resources Information Center

    Green, Elizabeth G.; Yates, Laura H.

    "Utilization of Skills in the Care of the Patient with Common, Well-Defined Health Deviations I" (NS 217) is an associate degree nursing course offered at Chattanooga State Technical Community College to help students develop new competencies necessary for the care of patients with deviations of the cardiovascular, endocrine, integumentary, and…

  13. Tropomodulin isoforms utilize specific binding functions to modulate dendrite development.

    PubMed

    Gray, Kevin T; Suchowerska, Alexandra K; Bland, Tyler; Colpan, Mert; Wayman, Gary; Fath, Thomas; Kostyukova, Alla S

    2016-06-01

    Tropomodulins (Tmods) cap F-actin pointed ends and have altered expression in the brain in neurological diseases. The function of Tmods in neurons has been poorly studied and their role in neurological diseases is entirely unknown. In this article, we show that Tmod1 and Tmod2, but not Tmod3, are positive regulators of dendritic complexity and dendritic spine morphology. Tmod1 increases dendritic branching distal from the cell body and the number of filopodia/thin spines. Tmod2 increases dendritic branching proximal to the cell body and the number of mature dendritic spines. Tmods utilize two actin-binding sites and two tropomyosin (Tpm)-binding sites to cap F-actin. Overexpression of Tmods with disrupted Tpm-binding sites indicates that Tmod1 and Tmod2 differentially utilize their Tpm- and actin-binding sites to affect morphology. Disruption of Tmod1's Tpm-binding sites abolished the overexpression phenotype. In contrast, overexpression of the mutated Tmod2 caused the same phenotype as wild type overexpression. Proximity ligation assays indicate that the mutated Tmods are shuttled similarly to wild type Tmods. Our data begins to uncover the roles of Tmods in neural development and the mechanism by which Tmods alter neural morphology. These observations in combination with altered Tmod expression found in several neurological diseases also suggest that dysregulation of Tmod expression may be involved in the pathology of these diseases. © 2016 Wiley Periodicals, Inc. PMID:27126680

  14. Self-defining future projections: exploring the identity function of thinking about the future.

    PubMed

    D'Argembeau, Arnaud; Lardi, Claudia; Van der Linden, Martial

    2012-01-01

    The act of projecting oneself into meaningful future events may significantly contribute to a person's sense of self and identity. Yet if the role of memories, in particular self-defining memories (SDMs), in grounding the self is now well established, the identity function of anticipated future events has received comparatively little attention. This article introduces the construct of self-defining future projection (SDFP) to address this issue. Two studies show that people can readily identify significant future events that they frequently think about and that convey core information about who they are as individuals. Furthermore, a person's particular style of constructing SDMs is similarly manifested in SDFPs, suggesting that both types of events can be used to ground the self. Notably, people who display a stronger tendency to extract meaning from their past experiences also reflect more about the potential implications of imagined future events. The results further demonstrate that SDMs and SDFPs both give rise to a strong sense of personal continuity over time and are meaningfully related to self-esteem. Together these findings lend support to the idea that a person's sense of self and identity is in part nourished by the anticipation of significant future events.

  15. miR clusters target cellular functional complexes by defining their degree of regulatory freedom.

    PubMed

    Haier, Jörg; Ströse, Anda; Matuszcak, Christiane; Hummel, Richard

    2016-06-01

    Using the two paralog miR-23∼27∼24 clusters as an example and combining experimental and clinical data in a systematical approach to microRNA (miR) function and dysregulation, a complex picture of their roles in cancer is drawn. Various findings appear to be contradictory to a larger extent and cannot be fully explained by the classical regulatory network models and feedback loops that are mainly considered by one-to-one regulatory interactions of the involved molecules. Here, we propose an extended model of the regulatory role of miRs that, at least, supplements the usually considered single/oligo-target regulation of certain miRs. The cellular availability of the participating miR members in this model reflects an upper hierarchy level of intracellular and extracellular environmental influences, such as neighboring cells, soluble factors, hypoxia, chemotherapeutic drugs, and irradiation, among others. The novel model is based on the understanding of cellular functional complexes, such as for apoptosis, migration, and proliferation. These complexes consist of many regulatory components that can be targeted by miR cluster members to a different extent but may affect the functional complex in different ways. We propose that the final miR-related effect is a result of the possible degree of regulatory freedom provided by the miR effects on the whole functional complex structure. This degree of regulatory freedom defines to which extent the cellular functional complex can react in response to regulatory triggers, also understood as sensitization (more regulatory response options) or de-sensitization (less regulatory response options) of the system rather than single molecules.

  16. Defining Recovery from an Eating Disorder: Conceptualization, Validation, and Examination of Psychosocial Functioning and Psychiatric Comorbidity

    PubMed Central

    Bardone-Cone, Anna M.; Harney, Megan B.; Maldonado, Christine R.; Lawson, Melissa A.; Robinson, D. Paul; Smith, Roma; Tosh, Aneesh

    2009-01-01

    Conceptually, eating disorder recovery should include physical, behavioral, and psychological components, but such a comprehensive approach has not been consistently employed. Guided by theory and recent recovery research, we identified a “fully recovered” group (n=20) based on physical (body mass index), behavioral (absence of eating disorder behaviors), and psychological (Eating Disorder Examination-Questionnaire) indices, and compared them with groups of partially recovered (n=15), active eating disorder (n=53), and healthy controls (n=67). The fully recovered group was indistinguishable from controls on all eating disorder-related measures used, while the partially recovered group was less disordered than the active eating disorder group on some measures, but not on body image. Regarding psychosocial functioning, both the fully and partially recovered groups had psychosocial functioning similar to the controls, but there was a pattern of more of the partially recovered group reporting eating disorder aspects interfering with functioning. Regarding other psychopathology, the fully recovered group was no more likely than the controls to experience current Axis I pathology, but they did have elevated rates of current anxiety disorder. Results suggest that a stringent definition of recovery from an eating disorder is meaningful. Clinical implications and future directions regarding defining eating disorder recovery are discussed. PMID:19945094

  17. Correlation of Theory and Function in Well-Defined Bimetallic Electrocatalysts - Final Report

    SciTech Connect

    Crooks, Richard M.

    2014-06-05

    The objective of this research proposal was to correlate the structure of nanoparticles that are comprised of ~100-200 atoms to their electrocatalytic function. This objective was based on the growing body of evidence suggesting that catalytic properties can be tailored through controlled synthesis of nanoparticles. What has been missing from many of these studies, and what we are contributing, is a model catalyst that is sufficiently small, structurally well-defined, and well-characterized that its function can be directly predicted by theory. Specifically, our work seeks to develop a fundamental and detailed understanding of the relationship between the structure of nanoscopic oxygen-reduction catalysts and their function. We assembled a team with expertise in theory, synthesis, and advanced characterization methods to address the primary objective of this project. We anticipated the outcomes of the study to be: (1) a better theoretical understanding of how nanoparticle structure affects catalytic properties; (2) the development of advanced, in-situ and ex-situ, atomic-scale characterization methods that are appropriate for particles containing about 100 atoms; and (3) improved synthetic methods that produce unique nanoparticle structures that can be used to test theoretical predictions. During the project period, we have made excellent progress on all three fronts.

  18. The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional Roles.

    PubMed

    Azulay, Aharon; Itskovits, Eyal; Zaslaver, Alon

    2016-09-01

    A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of C. elegans worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available. PMID:27606684

  19. The C. elegans Connectome Consists of Homogenous Circuits with Defined Functional Roles

    PubMed Central

    Azulay, Aharon; Zaslaver, Alon

    2016-01-01

    A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of C. elegans worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available. PMID:27606684

  20. Defining the players in higher-order networks: predictive modeling for reverse engineering functional influence networks.

    PubMed

    McDermott, Jason E; Archuleta, Michelle; Stevens, Susan L; Stenzel-Poore, Mary P; Sanfilippo, Antonio

    2011-01-01

    Determining biological network dependencies that can help predict the behavior of a system given prior observations from high-throughput data is a very valuable but difficult task, especially in the light of the ever-increasing volume of experimental data. Such an endeavor can be greatly enhanced by considering regulatory influences on co-expressed groups of genes representing functional modules, thus constraining the number of parameters in the system. This allows development of network models that are predictive of system dynamics. We first develop a predictive network model of the transcriptomics of whole blood from a mouse model of neuroprotection in ischemic stroke, and show that it can accurately predict system behavior under novel conditions. We then use a network topology approach to expand the set of regulators considered and show that addition of topological bottlenecks improves the performance of the predictive model. Finally, we explore how improvements in definition of functional modules may be achieved through an integration of inferred network relationships and functional relationships defined using Gene Ontology similarity. We show that appropriate integration of these two types of relationships can result in models with improved performance.

  1. Functional Myotube Formation from Adult Rat Satellite Cells in a Defined Serum-free System

    PubMed Central

    McAleer, Christopher W.; Rumsey, John W.; Stancescu, Maria; Hickman, James J.

    2016-01-01

    This manuscript describes the development of a culture system whereby mature contracting myotubes were formed from adult rat derived satellite cells. Satellite cells, extracted from the Tibialis Anterior (TA) of adult rats, were grown in defined serum-free growth and differentiation media, on a non-biological substrate, N-1[3-trimethoxysilyl propyl] diethylenetriamine. Myotubes were evaluated morphologically and immunocytochemically, using MyHC specific antibodies, as well as functionally using patch clamp electrophysiology to measure ion channel activity. Results indicated the establishment of the rapid expression of adult myosin isoforms that contrasts to their slow development in embryonic cultures. This culture system has applications in the understanding and treatment of age related muscle myopathy, muscular dystrophy, and for skeletal muscle engineering by providing a more relevant phenotype for both in vitro and in vivo applications. PMID:25683642

  2. Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities.

    PubMed

    Misra, Santosh K; Chang, Huei-Huei; Mukherjee, Prabuddha; Tiwari, Saumya; Ohoka, Ayako; Pan, Dipanjan

    2015-10-14

    A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2-250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400-20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis.

  3. Chromatin states reveal functional associations for globally defined transcription start sites in four human cell lines

    PubMed Central

    2014-01-01

    Background Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects. Results Transcription start sites can be distinguished by chromatin states defined by specific combinations of both chromatin mark enrichment and the profile shapes of these chromatin marks. The observed patterns can be associated with cellular functions and processes, and they also show association with expression level, location relative to nearby genes, and CpG content. In particular we find a substantial number of repressed inter- and intra-genic transcription start sites enriched for active chromatin marks and Pol II, and these sites are strongly associated with immediate-early response processes and cell signaling. Associations between start sites with similar chromatin patterns are validated by significant correlations in their global expression profiles. Conclusions The results confirm the link between chromatin state and cellular function for expressed transcripts, and also indicate that active chromatin states at repressed transcripts may poise transcripts for rapid activation during immune response. PMID:24669905

  4. Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities

    PubMed Central

    Misra, Santosh K.; Chang, Huei-Huei; Mukherjee, Prabuddha; Tiwari, Saumya; Ohoka, Ayako; Pan, Dipanjan

    2015-01-01

    A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2–250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400–20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis. PMID:26462751

  5. Regulating Biocompatibility of Carbon Spheres via Defined Nanoscale Chemistry and a Careful Selection of Surface Functionalities

    NASA Astrophysics Data System (ADS)

    Misra, Santosh K.; Chang, Huei-Huei; Mukherjee, Prabuddha; Tiwari, Saumya; Ohoka, Ayako; Pan, Dipanjan

    2015-10-01

    A plethora of nanoarchitectures have been evaluated preclincially for applications in early detection and treatment of diseases at molecular and cellular levels resulted in limited success of their clinical translation. It is important to identify the factors that directly or indirectly affect their use in human. We bring a fundamental understanding of how to adjust the biocompatibility of carbon based spherical nanoparticles (CNPs) through defined chemistry and a vigilant choice of surface functionalities. CNPs of various size are designed by tweaking size (2-250 nm), surface chemistries (positive, or negatively charged), molecular chemistries (linear, dendritic, hyperbranched) and the molecular weight of the coating agents (MW 400-20 kDa). A combination of in vitro assays as tools were performed to determine the critical parameters that may trigger toxicity. Results indicated that hydrodynamic sizes are potentially not a risk factor for triggering cellular and systemic toxicity, whereas the presence of a highly positive surface charge and increasing molecular weight enhance the chance of inducing complement activation. Bare and carboxyl-terminated CNPs did present some toxicity at the cellular level which, however, is not comparable to those caused by positively charged CNPs. Similarly, negatively charged CNPs with hydroxyl and carboxylic functionalities did not cause any hemolysis.

  6. Arabidopsis hot mutants define multiple functions required for acclimation to high temperatures.

    PubMed

    Hong, Suk-Whan; Lee, Ung; Vierling, Elizabeth

    2003-06-01

    Plants acquire thermotolerance to lethal high temperatures if first exposed to moderately high temperature or if temperature is increased gradually to an otherwise lethal temperature. We have taken a genetic approach to dissecting acquired thermotolerance by characterizing loss-of-function thermotolerance mutants in Arabidopsis. In previous work, we identified single recessive alleles of four loci required for thermotolerance of hypocotyl elongation, hot1-1, hot2-1, hot3-1, and hot4-1. Completed screening of M2 progeny from approximately 2500 M1 plants has now identified new alleles of three of these original loci, along with three new loci. The low mutant frequency suggests that a relatively small number of genes make a major contribution to this phenotype or that other thermotolerance genes encode essential or redundant functions. Further analysis of the original four loci was performed to define the nature of their thermotolerance defects. Although the HOT1 locus was shown previously to encode a major heat shock protein (Hsp), Hsp101, chromosomal map positions indicate that HOT2, 3, and 4 do not correspond to major Hsp or heat shock transcription factor genes. Measurement of thermotolerance at different growth stages reveals that the mutants have growth stage-specific heat sensitivity. Analysis of Hsp accumulation shows that hot2 and hot4 produce normal levels of Hsps, whereas hot3 shows reduced accumulation. Thermotolerance of luciferase activity and of ion leakage also varies in the mutants. These data provide the first direct genetic evidence, to our knowledge, that distinct functions, independent of Hsp synthesis, are required for thermotolerance, including protection of membrane integrity and recovery of protein activity/synthesis. PMID:12805605

  7. Defining patch mosaic functional types to predict invasion patterns in a forest landscape.

    PubMed

    Chabrerie, Olivier; Roulier, Frédéric; Hoeblich, Hélène; Sebert-Cuvillier, Emmanuelle; Closset-Kopp, Déborah; Leblanc, Isabelle; Jaminon, Jérôme; Decocq, Guillaume

    2007-03-01

    Alien plant invasions contribute significantly to global changes by often affecting biodiversity and ecosystem processes. Operational methods for identifying landscape attributes that promote or constrain plant invasions are urgently needed to predict their future spread and manage them efficiently. We combined landscape and functional ecology concepts to define patch mosaic functional types (PMFTs) as groups of cells showing the same response to a plant invasion in a heterogeneous forest landscape. The invasion of a European temperate forest by the American black cherry (Prunus serotina) has been chosen as a case study. A set of variables was collected, mapped using a Geographic Information System, and analyzed with multivariate analyses to correlate landscape traits with Prunus serotina abundance in each cell of a grid overlaid on the forest. A risk index was derived and mapped for three invasion levels: seedling colonization, tree establishment, and ecosystem invasion. Five PMFTs were identified and characterized by a set of traits related to soil properties, land use, disturbance, and invasion history. Scots pine plantations on podzols were the most invasible, while cells dominated by hydromorphic or calcareous soils were the most resistant. Most colonized patch mosaics provided suitable conditions for future establishment and invasion. Being strongly spatially connected, suitable patches provide corridors for Prunus serotina to colonize new parts of the forest. Conversely, the most resistant PMFTs were spatially agglomerated in the south of the forest and could act as a barrier. Colonization, establishment, and invasion risk maps were finally obtained by combining partial risks associated with each landscape trait at the cell scale. Within a heterogeneous landscape, we defined and organized PMFTs into a hierarchy, according to their associated risk for colonization, establishment, or invasion by a given invasive species. Each hierarchical level should be

  8. VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

    PubMed Central

    Cianfanelli, Francesca R.; Alcoforado Diniz, Juliana; Guo, Manman; De Cesare, Virginia; Trost, Matthias; Coulthurst, Sarah J.

    2016-01-01

    The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently (‘specialised’) or non-covalently (‘cargo’ effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a ‘core’ T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the

  9. Applying Utility Functions to Adaptation Planning for Home Automation Applications

    NASA Astrophysics Data System (ADS)

    Bratskas, Pyrros; Paspallis, Nearchos; Kakousis, Konstantinos; Papadopoulos, George A.

    A pervasive computing environment typically comprises multiple embedded devices that may interact together and with mobile users. These users are part of the environment, and they experience it through a variety of devices embedded in the environment. This perception involves technologies which may be heterogeneous, pervasive, and dynamic. Due to the highly dynamic properties of such environments, the software systems running on them have to face problems such as user mobility, service failures, or resource and goal changes which may happen in an unpredictable manner. To cope with these problems, such systems must be autonomous and self-managed. In this chapter we deal with a special kind of a ubiquitous environment, a smart home environment, and introduce a user-preference-based model for adaptation planning. The model, which dynamically forms a set of configuration plans for resources, reasons automatically and autonomously, based on utility functions, on which plan is likely to best achieve the user's goals with respect to resource availability and user needs.

  10. Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin.

    PubMed

    Glenn, Thomas D; Talbot, William S

    2013-08-01

    In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin.

  11. Requirements for Defining Utility Drive Cycles: An Exploratory Analysis of Grid Frequency Regulation Data for Establishing Battery Performance Testing Standards

    SciTech Connect

    Hafen, Ryan P.; Vishwanathan, Vilanyur V.; Subbarao, Krishnappa; Kintner-Meyer, Michael CW

    2011-10-19

    Battery testing procedures are important for understanding battery performance, including degradation over the life of the battery. Standards are important to provide clear rules and uniformity to an industry. The work described in this report addresses the need for standard battery testing procedures that reflect real-world applications of energy storage systems to provide regulation services to grid operators. This work was motivated by the need to develop Vehicle-to-Grid (V2G) testing procedures, or V2G drive cycles. Likewise, the stationary energy storage community is equally interested in standardized testing protocols that reflect real-world grid applications for providing regulation services. As the first of several steps toward standardizing battery testing cycles, this work focused on a statistical analysis of frequency regulation signals from the Pennsylvania-New Jersey-Maryland Interconnect with the goal to identify patterns in the regulation signal that would be representative of the entire signal as a typical regulation data set. Results from an extensive time-series analysis are discussed, and the results are explained from both the statistical and the battery-testing perspectives. The results then are interpreted in the context of defining a small set of V2G drive cycles for standardization, offering some recommendations for the next steps toward standardizing testing protocols.

  12. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    DOE PAGES

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; et al

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits themore » utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.« less

  13. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    SciTech Connect

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

  14. Role of Utility and Inference in the Evolution of Functional Information

    PubMed Central

    Sharov, Alexei A.

    2009-01-01

    Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism’s behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are

  15. Utility of shallow-water ATRIS images in defining biogeologic processes and self-similarity in skeletal scleractinia, Florida reefs

    USGS Publications Warehouse

    Lidz, B.H.; Brock, J.C.; Nagle, D.B.

    2008-01-01

    A recently developed remote-sensing instrument acquires high-quality digital photographs in shallow-marine settings within water depths of 15 m. The technology, known as the Along-Track Reef-Imaging System, provides remarkably clear, georeferenced imagery that allows visual interpretation of benthic class (substrates, organisms) for mapping coral reef habitats, as intended. Unforeseen, however, are functions new to the initial technologic purpose: interpr??table evidence for real-time biogeologic processes and for perception of scaled-up skeletal self-similarity of scleractinian microstructure. Florida reef sea trials lacked the grid structure required to map contiguous habitat and submarine topography. Thus, only general observations could be made relative to times and sites of imagery. Degradation of corals was nearly universal; absence of reef fish was profound. However, ???1% of more than 23,600 sea-trial images examined provided visual evidence for local environs and processes. Clarity in many images was so exceptional that small tracks left by organisms traversing fine-grained carbonate sand were visible. Other images revealed a compelling sense, not yet fully understood, of the microscopic wall structure characteristic of scleractinian corals. Conclusions drawn from classifiable images are that demersal marine animals, where imaged, are oblivious to the equipment and that the technology has strong capabilities beyond mapping habitat. Imagery acquired along predetermined transects that cross a variety of geomorphic features within depth limits will ( 1) facilitate construction of accurate contour maps of habitat and bathymetry without need for ground-truthing, (2) contain a strong geologic component of interpreted real-time processes as they relate to imaged topography and regional geomorphology, and (3) allow cost-effective monitoring of regional- and local-scale changes in an ecosystem by use of existing-image global-positioning system coordinates to re

  16. Eliciting Utility Functions for Validating Course Placement Systems.

    ERIC Educational Resources Information Center

    Sawyer, Richard

    Course placement systems in postsecondary education consist of an assessment component to estimate students' probability of success in standard first-year courses and an instructional component in which underprepared students are taught the skills and knowledge they need to succeed in the standard courses. Student success is usually defined in…

  17. Utilization of Peanut Skin Extracts as Functional Food Ingredients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanut skins are a by-product of the blanching industry that have not been utilized to their full potential. They have been found to contain significant quantities of compounds containing phenolic moieties such as catechins, procyanidins, and other polyphenols that have positive associations with h...

  18. The theta-syllable: a unit of speech information defined by cortical function

    PubMed Central

    Ghitza, Oded

    2013-01-01

    A recent commentary (Oscillators and syllables: a cautionary note. Cummins, 2012) questions the validity of a class of speech perception models inspired by the possible role of neuronal oscillations in decoding speech (e.g., Ghitza, 2011; Giraud and Poeppel, 2012). In arguing against the approach, Cummins raises a cautionary flag “from a phonetician's point of view.” Here we respond to his arguments from an auditory processing viewpoint, referring to a phenomenological model of Ghitza (2011) taken as a representative of the criticized approach. We shall conclude by proposing the theta-syllable as an information unit defined by cortical function—an alternative to the conventional, ambiguously defined syllable. In the large context, the resulting discussion debate should be viewed as a subtext of acoustic and auditory phonetics vs. articulatory and motor theories of speech reception. PMID:23519170

  19. Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle.

    PubMed

    Littlejohn, Mathew D; Henty, Kristen M; Tiplady, Kathryn; Johnson, Thomas; Harland, Chad; Lopdell, Thomas; Sherlock, Richard G; Li, Wanbo; Lukefahr, Steven D; Shanks, Bruce C; Garrick, Dorian J; Snell, Russell G; Spelman, Richard J; Davis, Stephen R

    2014-01-01

    Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation.

  20. Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle

    PubMed Central

    Littlejohn, Mathew D.; Henty, Kristen M.; Tiplady, Kathryn; Johnson, Thomas; Harland, Chad; Lopdell, Thomas; Sherlock, Richard G.; Li, Wanbo; Lukefahr, Steven D.; Shanks, Bruce C.; Garrick, Dorian J.; Snell, Russell G.; Spelman, Richard J.; Davis, Stephen R.

    2014-01-01

    Lactation, hair development and homeothermy are characteristic evolutionary features that define mammals from other vertebrate species. Here we describe the discovery of two autosomal dominant mutations with antagonistic, pleiotropic effects on all three of these biological processes, mediated through the prolactin signalling pathway. Most conspicuously, mutations in prolactin (PRL) and its receptor (PRLR) have an impact on thermoregulation and hair morphology phenotypes, giving prominence to this pathway outside of its classical roles in lactation. PMID:25519203

  1. Defining the Physiological Factors that Contribute to Postflight Changes in Functional Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Arzeno, N.; Buxton, R.; Feiveson, A. H.; Kofman, I.; Lawrence, E.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts, S. H.; Ploutz-Snyder, L.; Reschke, M. F.; Ryder, J.; Spiering, B. A.; Stenger, M. B.; Wood, S.

    2009-01-01

    Astronauts experience alterations in multiple physiological systems due to exposure to the microgravity conditions of space flight. These physiological changes include sensorimotor disturbances, cardiovascular deconditioning and loss of muscle mass and strength. These changes might affect the ability of crewmembers to perform critical mission tasks immediately after landing on lunar and Martian surfaces. To date, changes in functional performance have not been systematically studied or correlated with physiological changes. To understand how changes in physiological function impact functional performance an interdisciplinary pre/postflight testing regimen (Functional Task Test, FTT) has been developed that systematically evaluates both astronaut postflight functional performance and related physiological changes. The overall objective of the FTT is to identify the key underlying physiological factors that contribute to performance of functional tests that are representative of critical mission tasks. This study will identify which physiological systems contribute the most to impaired performance on each functional test. This will allow us to identify the physiological systems that play the largest role in decrement in functional performance. Using this information we can then design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight. The functional test battery was designed to address high priority tasks identified by the Constellation program as critical for mission success. The set of functional tests making up the FTT include the: 1) Seat Egress and Walk Test, 2) Ladder Climb Test, 3) Recovery from Fall/Stand Test, 4) Rock Translation Test, 5) Jump Down Test, 6) Torque Generation Test, and 7) Construction Activity Board Test. Corresponding physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor

  2. Ecological function as a target for ecosystem-based management: Defining when change matters in decision making

    EPA Science Inventory

    Ecosystem-based management (EBM) accounts for both direct and indirect drivers of ecological change for decision making. Just as with direct management of a resource, EBM requires a definition of management thresholds that define when change in function is sufficient to merit ma...

  3. Combining data on health care utilization and socioeconomic status of a defined population: use of a population oriented health information system for regional planning.

    PubMed

    Brommels, M; Heinonen, M O; Tuomola, S

    1987-01-01

    Health services planning on a regional or national level needs information on health care utilization as well as data on the population to be served. Health or hospital information systems usually cover services provision and utilization, and population data for planning purposes must be obtained from other sources. In the health information system presented, hospital performance data are combined with census and socioeconomic data of the population. That makes cautious analysis of reasons for variation in health care utilization within the planning area possible. The HIS is regional, including 11 health care providers, and population based, linking data to municipality (38 in all). The system is described, including its structure, input registration, file content and output formats. An output example is presented. Necessary conditions for use of the HIS in planning activities are that the corresponding health care delivery system is comprehensive, the population served well defined, and that good control of patient flow and user behaviour is achieved. Use is limited by the character of information stored in the HIS: it is registered retrospectively and by routine. In a system covering various hospitals and municipalities, engaging different types of clerical and health care personnel, data reliability is also a critical issue.

  4. Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility

    PubMed Central

    Morris, Laurel S.; Kundu, Prantik; Dowell, Nicholas; Mechelmans, Daisy J.; Favre, Pauline; Irvine, Michael A.; Robbins, Trevor W.; Daw, Nathaniel; Bullmore, Edward T.; Harrison, Neil A.; Voon, Valerie

    2016-01-01

    Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum – VS, ventral tegmental area – VTA), motor (supplementary motor areas – SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex – mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex – lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex – dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control. PMID:26673945

  5. Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility.

    PubMed

    Morris, Laurel S; Kundu, Prantik; Dowell, Nicholas; Mechelmans, Daisy J; Favre, Pauline; Irvine, Michael A; Robbins, Trevor W; Daw, Nathaniel; Bullmore, Edward T; Harrison, Neil A; Voon, Valerie

    2016-01-01

    Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum - VS, ventral tegmental area - VTA), motor (supplementary motor areas - SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex - mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex - lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex - dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control. PMID:26673945

  6. Defining functional changes in the brain caused by targeted stereotaxic radiosurgery

    PubMed Central

    Parihar, Vipan K.; Acharya, Munjal M.; Roa, Dante E.; Bosch, Omar; Christie, Lori-Ann; Limoli, Charles L.

    2013-01-01

    Brain tumor patients routinely undergo cranial radiotherapy, and while beneficial, this treatment often results in debilitating cognitive dysfunction. This serious and unresolved problem has at present, no clinical recourse, and has driven our efforts to more clearly define the consequences of different brain irradiation paradigms on specific indices of cognitive performance and on the underlying cellular mechanisms believed to affect these processes. To accomplish this we have developed the capability to deliver highly focused X-ray beams to small and precisely defined volumes of the athymic rat brain, thereby providing more realistic simulations of clinical irradiation scenarios. Using this technique, termed stereotaxic radiosurgery, we evaluated the cognitive consequences of irradiation targeted to the hippocampus in one or both hemispheres of the brain, and compared that to whole brain irradiation. While whole brain irradiation was found to elicit significant deficits in novel place recognition and fear conditioning, standard platforms for quantifying hippocampal and non-hippocampal decrements, irradiation targeted to both hippocampi was only found to elicit deficits in fear conditioning. Cognitive decrements were more difficult to demonstrate in animals subjected to unilateral hippocampal ablation. Immunohistochemical staining for newly born immature (doublecortin positive) and mature (NeuN positive) neurons confirmed our capability to target irradiation to the neurogenic regions of the hippocampus. Stereotaxic radiosurgery (SRS) of the ipsilateral hemisphere reduced significantly the number of doublecortin and NeuN positive neurons by 80% and 27% respectively. Interestingly, neurogenesis on the contralateral side was upregulated in response to stereotaxic radiosurgery, where the number of doublecortin and NeuN positive neurons increased by 22% and 36% respectively. Neuroinflammation measured by immunostaining for activated microglia (ED1 positive cells) was

  7. TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

    SciTech Connect

    Bowen, S; Miyaoka, R; Kinahan, P; Sandison, G; Vesselle, H; Nyflot, M; Apisarnthanarax, S; Saini, J; Wong, T

    2014-06-15

    Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined by liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with proton

  8. A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

    PubMed Central

    Patel, Asha K.; Celiz, Adam D.; Rajamohan, Divya; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.

    2016-01-01

    Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 µM in cardiomyocytes cultured on the co-polymer compared to 0.5 µM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials. PMID:26005764

  9. A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays.

    PubMed

    Patel, Asha K; Celiz, Adam D; Rajamohan, Divya; Anderson, Daniel G; Langer, Robert; Davies, Martyn C; Alexander, Morgan R; Denning, Chris

    2015-08-01

    Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 μM in cardiomyocytes cultured on the co-polymer compared to 0.5 μM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.

  10. Using siRNA to define functional interactions between melanopsin and multiple G Protein partners.

    PubMed

    Hughes, Steven; Jagannath, Aarti; Hickey, Doron; Gatti, Silvia; Wood, Matthew; Peirson, Stuart N; Foster, Russell G; Hankins, Mark W

    2015-01-01

    Melanopsin expressing photosensitive retinal ganglion cells (pRGCs) represent a third class of ocular photoreceptors and mediate a range of non-image forming responses to light. Melanopsin is a G protein coupled receptor (GPCR) and existing data suggest that it employs a membrane bound signalling cascade involving Gnaq/11 type G proteins. However, to date the precise identity of the Gα subunits involved in melanopsin phototransduction remains poorly defined. Here we show that Gnaq, Gna11 and Gna14 are highly co-expressed in pRGCs of the mouse retina. Furthermore, using RNAi based gene silencing we show that melanopsin can signal via Gnaq, Gna11 or Gna14 in vitro, and demonstrate that multiple members of the Gnaq/11 subfamily, including Gna14 and at least Gnaq or Gna11, can participate in melanopsin phototransduction in vivo and contribute to the pupillary light responses of mice lacking rod and cone photoreceptors. This diversity of G protein interactions suggests additional complexity in the melanopsin phototransduction cascade and may provide a basis for generating the diversity of light responses observed from pRGC subtypes.

  11. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA.

    PubMed

    Kobielak, Krzysztof; Pasolli, H Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-11-10

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/beta-catenin-regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated beta-catenin. This places the block downstream from Lef1 expression but upstream from beta-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized beta-catenin to activate the hair specific keratin genes and generate the hair shaft.

  12. Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

    PubMed Central

    Gilligan, Patrick C.; Kumari, Pooja; Lim, Shimin; Cheong, Albert; Chang, Alex; Sampath, Karuna

    2011-01-01

    RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins. PMID:21149265

  13. Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA

    PubMed Central

    Kobielak, Krzysztof; Pasolli, H. Amalia; Alonso, Laura; Polak, Lisa; Fuchs, Elaine

    2003-01-01

    Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft. PMID:14610062

  14. Coverage-driven dissociation of azobenzene on Cu(111): a route towards defined surface functionalization.

    PubMed

    Willenbockel, Martin; Maurer, Reinhard J; Bronner, Christopher; Schulze, Michael; Stadtmüller, Benjamin; Soubatch, Serguei; Tegeder, Petra; Reuter, Karsten; Stefan Tautz, F

    2015-10-25

    We investigate the surface-catalyzed dissociation of the archetypal molecular switch azobenzene on the Cu(111) surface. Based on X-ray photoelectron spectroscopy, normal incidence X-ray standing waves and density functional theory calculations a detailed picture of the coverage-induced formation of phenyl nitrene from azobenzene is presented. Furthermore, a comparison to the azobenzene/Ag(111) interface provides insight into the driving force behind the dissociation on Cu(111). The quantitative decay of azobenzene paves the way for the creation of a defect free, covalently bonded monolayer. Our work suggests a route of surface functionalization via suitable azobenzene derivatives and the on surface synthesis concept, allowing for the creation of complex immobilized molecular systems. PMID:26340405

  15. Using riboswitches to regulate gene expression and define gene function in mycobacteria.

    PubMed

    Van Vlack, Erik R; Seeliger, Jessica C

    2015-01-01

    Mycobacteria include both environmental species and many pathogenic species such as Mycobacterium tuberculosis, an intracellular pathogen that is the causative agent of tuberculosis in humans. Inducible gene expression is a powerful tool for examining gene function and essentiality, both in in vitro culture and in host cell infections. The theophylline-inducible artificial riboswitch has recently emerged as an alternative to protein repressor-based systems. The riboswitch is translationally regulated and is combined with a mycobacterial promoter that provides transcriptional control. We here provide methods used by our laboratory to characterize the riboswitch response to theophylline in reporter strains, recombinant organisms containing riboswitch-regulated endogenous genes, and in host cell infections. These protocols should facilitate the application of both existing and novel artificial riboswitches to the exploration of gene function in mycobacteria. PMID:25605389

  16. Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

    PubMed

    Yao, Q

    2001-06-28

    [reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety. PMID:11418051

  17. Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

    PubMed

    Yao, Q

    2001-06-28

    [reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety.

  18. Utility of an abbreviated questionnaire to identify individuals with ADHD at risk for functional impairments

    PubMed Central

    Biederman, Joseph; Petty, Carter R.; Fried, Ronna; Doyle, Alysa E.; Mick, Eric; Aleardi, Megan; Monuteaux, Michael C.; Seidman, Larry J.; Spencer, Thomas; Faneuil, Alicia R.; Holmes, Lauren; Faraone, Stephen V.

    2008-01-01

    Objective To discern whether a subset of items from the 99-item Current Behavior Scale (CBS) of behaviorally defined executive function deficits (EFDs) in adults with attention-deficit/hyperactivity disorder (ADHD) can identify a group at risk for poor outcome. Methods Subjects were 200 adults with ADHD participating in a family study of ADHD in adults. Factor analysis was used to reduce the number of items in the 99-item CBS. Results The one factor solution provided 8 items with factor loadings above 0.70. This abbreviated set of items was highly correlated with the 99-item CBS (0.91) and was similarly related to functional outcomes compared to the 99-item CBS (average correlation of 0.30 versus 0.32). Conclusion For adults with ADHD, a set of 8 empirically derived from the CBS similarly correlated with negative outcomes compared to the 99-item CBS, raising the possibility of utilization as a mechanism for identification of EFDs in adults with ADHD. PMID:17335849

  19. Achieving functional restorations utilizing a new Ceromer system.

    PubMed

    Trinkner, T

    1997-01-01

    The advent of pressed ceramic restorations (IPS Empress, Ivoclar Williams, Amherst, NY) has driven dental therapy to continuously strive for more aesthetic and functional materials. The dental profession requires restorations to exhibit strength, natural color, wear resistance, marginal integrity, and ease of fabrication in the restorative therapies selected. With the introduction of a new ceromer and fiber-reinforced composite (FRC) system (Targis System, Ivoclar Williams, Amherst, NY), the replacement of a single tooth or multiple teeth with a FRC, metal-free bridge is now a suitable alternative to conventional dental therapy. This presentation will review the clinical protocol, material properties, and aesthetic characteristics of this new generation of restorative material.

  20. Defining conservation priorities for freshwater fishes according to taxonomic, functional, and phylogenetic diversity

    USGS Publications Warehouse

    Strecker, A.L.; Olden, J.D.; Whittier, Joanna B.; Paukert, C.P.

    2011-01-01

    To date, the predominant use of systematic conservation planning has been to evaluate and conserve areas of high terrestrial biodiversity. Although studies in freshwater ecosystems have received recent attention, research has rarely considered the potential tradeoffs between protecting different dimensions of biodiversity and the ecological processes that maintain diversity. We provide the first systematic prioritization for freshwaters (focusing on the highly threatened and globally distinct fish fauna of the Lower Colorado River Basin, USA) simultaneously considering scenarios of: taxonomic, functional, and phylogenetic diversity;contemporary threats to biodiversity (including interactions with nonnative species);and future climate change and human population growth. There was 75% congruence between areas of highest conservation priority for different aspects of biodiversity, suggesting that conservation efforts can concurrently achieve strong complementarity among all types of diversity. However, sizable fractions of the landscape were incongruent across conservation priorities for different diversity scenarios, underscoring the importance of considering multiple dimensions of biodiversity and highlighting catchments that contribute disproportionately to taxonomic, functional, and phylogenetic diversity in the region. Regions of projected human population growth were not concordant with conservation priorities;however, higher human population abundance will likely have indirect effects on native biodiversity by increasing demand for water. This will come in direct conflict with projected reductions in precipitation and warmer temperatures, which have substantial overlap with regions of high contemporary diversity. Native and endemic fishes in arid ecosystems are critically endangered by both current and future threats, but our results highlight the use of systematic conservation planning for the optimal allocation of limited resources that incorporates multiple

  1. Defining conservation priorities for freshwater fishes according to taxonomic, functional, and phylogenetic diversity

    USGS Publications Warehouse

    Strecker, Angela; Olden, Julian D.; Whittier, Joanna B.; Paukert, Craig P.

    2011-01-01

    To date, the predominant use of systematic conservation planning has been to evaluate and conserve areas of high terrestrial biodiversity. Although studies in freshwater ecosystems have received recent attention, research has rarely considered the potential trade-offs between protecting different dimensions of biodiversity and the ecological processes that maintain diversity. We provide the first systematic prioritization for freshwaters (focusing on the highly threatened and globally distinct fish fauna of the Lower Colorado River Basin, USA) simultaneously considering scenarios of: taxonomic, functional, and phylogenetic diversity; contemporary threats to biodiversity (including interactions with nonnative species); and future climate change and human population growth. There was 75% congruence between areas of highest conservation priority for different aspects of biodiversity, suggesting that conservation efforts can concurrently achieve strong complementarity among all types of diversity. However, sizable fractions of the landscape were incongruent across conservation priorities for different diversity scenarios, underscoring the importance of considering multiple dimensions of biodiversity and highlighting catchments that contribute disproportionately to taxonomic, functional, and phylogenetic diversity in the region. Regions of projected human population growth were not concordant with conservation priorities; however, higher human population abundance will likely have indirect effects on native biodiversity by increasing demand for water. This will come in direct conflict with projected reductions in precipitation and warmer temperatures, which have substantial overlap with regions of high contemporary diversity. Native and endemic fishes in arid ecosystems are critically endangered by both current and future threats, but our results highlight the use of systematic conservation planning for the optimal allocation of limited resources that incorporates

  2. The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes

    PubMed Central

    van Overbeek, Leonard S.; Berg, Gabriele; Pirttilä, Anna Maria; Compant, Stéphane; Campisano, Andrea; Döring, Matthias; Sessitsch, Angela

    2015-01-01

    SUMMARY All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions. PMID:26136581

  3. The Hidden World within Plants: Ecological and Evolutionary Considerations for Defining Functioning of Microbial Endophytes.

    PubMed

    Hardoim, Pablo R; van Overbeek, Leonard S; Berg, Gabriele; Pirttilä, Anna Maria; Compant, Stéphane; Campisano, Andrea; Döring, Matthias; Sessitsch, Angela

    2015-09-01

    All plants are inhabited internally by diverse microbial communities comprising bacterial, archaeal, fungal, and protistic taxa. These microorganisms showing endophytic lifestyles play crucial roles in plant development, growth, fitness, and diversification. The increasing awareness of and information on endophytes provide insight into the complexity of the plant microbiome. The nature of plant-endophyte interactions ranges from mutualism to pathogenicity. This depends on a set of abiotic and biotic factors, including the genotypes of plants and microbes, environmental conditions, and the dynamic network of interactions within the plant biome. In this review, we address the concept of endophytism, considering the latest insights into evolution, plant ecosystem functioning, and multipartite interactions.

  4. Flux Balance Analysis with Objective Function Defined by Proteomics Data-Metabolism of Mycobacterium tuberculosis Exposed to Mefloquine.

    PubMed

    Montezano, Daniel; Meek, Laura; Gupta, Rashmi; Bermudez, Luiz E; Bermudez, José C M

    2015-01-01

    We present a study of the metabolism of the Mycobacterium tuberculosis after exposure to antibiotics using proteomics data and flux balance analysis (FBA). The use of FBA to study prokaryotic organisms is well-established and allows insights into the metabolic pathways chosen by the organisms under different environmental conditions. To apply FBA a specific objective function must be selected that represents the metabolic goal of the organism. FBA estimates the metabolism of the cell by linear programming constrained by the stoichiometry of the reactions in an in silico metabolic model of the organism. It is assumed that the metabolism of the organism works towards the specified objective function. A common objective is the maximization of biomass. However, this goal is not suitable for situations when the bacterium is exposed to antibiotics, as the goal of organisms in these cases is survival and not necessarily optimal growth. In this paper we propose a new approach for defining the FBA objective function in studies when the bacterium is under stress. The function is defined based on protein expression data. The proposed methodology is applied to the case when the bacterium is exposed to the drug mefloquine, but can be easily extended to other organisms, conditions or drugs. We compare our method with an alternative method that uses experimental data for adjusting flux constraints. We perform comparisons in terms of essential enzymes and agreement using enzyme abundances. Results indicate that using proteomics data to define FBA objective functions yields less essential reactions with zero flux and lower error rates in prediction accuracy. With flux variability analysis we observe that overall variability due to alternate optima is reduced with the incorporation of proteomics data. We believe that incorporating proteomics data in the objective function used in FBA may help obtain metabolic flux representations that better support experimentally observed features

  5. Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

    PubMed Central

    Schaerli, Patrick; Willimann, Katharina; Lang, Alois B.; Lipp, Martin; Loetscher, Pius; Moser, Bernhard

    2000-01-01

    Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). Memory but not naive T cells from tonsils are CXCR5+ and migrate in response to the B cell–attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. Tonsillar CXCR5+ T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell–derived factor 1 (SDF-1). The involvement of tonsillar CXCR5+ T cells in humoral immune responses is suggested by their localization in the mantle and light zone germinal centers of B cell follicles and by the concomitant expression of activation and costimulatory markers, including CD69, HLA-DR, and inducible costimulator (ICOS). Peripheral blood CXCR5+ T cells also belong to the CD4+ memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. CXCR5+ T cells are very inefficient in the production of cytokines but potently induce antibody production during coculture with B cells. These properties portray CXCR5+ T cells as a distinct memory T cell subset with B cell helper function, designated here as follicular B helper T cells (TFH). PMID:11104798

  6. Highly reflective polymeric substrates functionalized utilizing atomic layer deposition

    SciTech Connect

    Zuzuarregui, Ana Gregorczyk, Keith E.; Coto, Borja; Ruiz de Gopegui, Unai; Barriga, Javier; Rodríguez, Jorge; Knez, Mato

    2015-08-10

    Reflective surfaces are one of the key elements of solar plants to concentrate energy in the receivers of solar thermal electricity plants. Polymeric substrates are being considered as an alternative to the widely used glass mirrors due to their intrinsic and processing advantages, but optimizing both the reflectance and the physical stability of polymeric mirrors still poses technological difficulties. In this work, polymeric surfaces have been functionalized with ceramic thin-films by atomic layer deposition. The characterization and optimization of the parameters involved in the process resulted in surfaces with a reflection index of 97%, turning polymers into a real alternative to glass substrates. The solution we present here can be easily applied in further technological areas where seemingly incompatible combinations of polymeric substrates and ceramic coatings occur.

  7. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors.

    PubMed

    Yang, Ruifeng; Zheng, Ying; Li, Ling; Liu, Shujing; Burrows, Michelle; Wei, Zhi; Nace, Arben; Herlyn, Meenhard; Cui, Rutao; Guo, Wei; Cotsarelis, George; Xu, Xiaowei

    2014-01-01

    Direct reprogramming provides a fundamentally new approach for the generation of patient-specific cells. Here, by screening a pool of candidate transcription factors, we identify that a combination of the three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes. Induced melanocytes (iMels) activate melanocyte-specific networks, express components of pigment production and delivery system and produce melanosomes. Human iMels properly integrate into the dermal-epidermal junction and produce and deliver melanin pigment to surrounding keratinocytes in a 3D organotypic skin reconstruct. Human iMels generate pigmented epidermis and hair follicles in skin reconstitution assays in vivo. The generation of iMels has important implications for studies of melanocyte lineage commitment, pigmentation disorders and cell replacement therapies. PMID:25510211

  8. Defining the face processing network: optimization of the functional localizer in fMRI.

    PubMed

    Fox, Christopher J; Iaria, Giuseppe; Barton, Jason J S

    2009-05-01

    Functional localizers that contrast brain signal when viewing faces versus objects are commonly used in functional magnetic resonance imaging studies of face processing. However, current protocols do not reliably show all regions of the core system for face processing in all subjects when conservative statistical thresholds are used, which is problematic in the study of single subjects. Furthermore, arbitrary variations in the applied thresholds are associated with inconsistent estimates of the size of face-selective regions-of-interest (ROIs). We hypothesized that the use of more natural dynamic facial images in localizers might increase the likelihood of identifying face-selective ROIs in individual subjects, and we also investigated the use of a method to derive the statistically optimal ROI cluster size independent of thresholds. We found that dynamic facial stimuli were more effective than static stimuli, identifying 98% (versus 72% for static) of ROIs in the core face processing system and 69% (versus 39% for static) of ROIs in the extended face processing system. We then determined for each core face processing ROI, the cluster size associated with maximum statistical face-selectivity, which on average was approximately 50 mm(3) for the fusiform face area, the occipital face area, and the posterior superior temporal sulcus. We suggest that the combination of (a) more robust face-related activity induced by a dynamic face localizer and (b) a cluster-size determination based on maximum face-selectivity increases both the sensitivity and the specificity of the characterization of face-related ROIs in individual subjects.

  9. Defining the face processing network: optimization of the functional localizer in fMRI.

    PubMed

    Fox, Christopher J; Iaria, Giuseppe; Barton, Jason J S

    2009-05-01

    Functional localizers that contrast brain signal when viewing faces versus objects are commonly used in functional magnetic resonance imaging studies of face processing. However, current protocols do not reliably show all regions of the core system for face processing in all subjects when conservative statistical thresholds are used, which is problematic in the study of single subjects. Furthermore, arbitrary variations in the applied thresholds are associated with inconsistent estimates of the size of face-selective regions-of-interest (ROIs). We hypothesized that the use of more natural dynamic facial images in localizers might increase the likelihood of identifying face-selective ROIs in individual subjects, and we also investigated the use of a method to derive the statistically optimal ROI cluster size independent of thresholds. We found that dynamic facial stimuli were more effective than static stimuli, identifying 98% (versus 72% for static) of ROIs in the core face processing system and 69% (versus 39% for static) of ROIs in the extended face processing system. We then determined for each core face processing ROI, the cluster size associated with maximum statistical face-selectivity, which on average was approximately 50 mm(3) for the fusiform face area, the occipital face area, and the posterior superior temporal sulcus. We suggest that the combination of (a) more robust face-related activity induced by a dynamic face localizer and (b) a cluster-size determination based on maximum face-selectivity increases both the sensitivity and the specificity of the characterization of face-related ROIs in individual subjects. PMID:18661501

  10. DEFINING THE PLAYERS IN HIGHER-ORDER NETWORKS: PREDICTIVE MODELING FOR REVERSE ENGINEERING FUNCTIONAL INFLUENCE NETWORKS

    SciTech Connect

    McDermott, Jason E.; Costa, Michelle N.; Stevens, S.L.; Stenzel-Poore, Mary; Sanfilippo, Antonio P.

    2011-01-20

    A difficult problem that is currently growing rapidly due to the sharp increase in the amount of high-throughput data available for many systems is that of determining useful and informative causative influence networks. These networks can be used to predict behavior given observation of a small number of components, predict behavior at a future time point, or identify components that are critical to the functioning of the system under particular conditions. In these endeavors incorporating observations of systems from a wide variety of viewpoints can be particularly beneficial, but has often been undertaken with the objective of inferring networks that are generally applicable. The focus of the current work is to integrate both general observations and measurements taken for a particular pathology, that of ischemic stroke, to provide improved ability to produce useful predictions of systems behavior. A number of hybrid approaches have recently been proposed for network generation in which the Gene Ontology is used to filter or enrich network links inferred from gene expression data through reverse engineering methods. These approaches have been shown to improve the biological plausibility of the inferred relationships determined, but still treat knowledge-based and machine-learning inferences as incommensurable inputs. In this paper, we explore how further improvements may be achieved through a full integration of network inference insights achieved through application of the Gene Ontology and reverse engineering methods with specific reference to the construction of dynamic models of transcriptional regulatory networks. We show that integrating two approaches to network construction, one based on reverse-engineering from conditional transcriptional data, one based on reverse-engineering from in situ hybridization data, and another based on functional associations derived from Gene Ontology, using probabilities can improve results of clustering as evaluated by a

  11. Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer

    PubMed Central

    Maxfield, Kimberly E.; Taus, Patrick J.; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K.; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W.

    2015-01-01

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer–testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology. PMID:26567849

  12. Plant functional types define magnitude of drought response in peatland CO2 exchange.

    PubMed

    Kuiper, Jan J; Mooij, Wolf M; Bragazza, Luca; Robroek, Bjorn J M

    2014-01-01

    Peatlands are important sinks for atmospheric carbon (C), yet the role of plant functional types (PFTs) for C sequestration under climatic perturbations is still unclear. A plant-removal experiment was used to study the importance of vascular PFTs for the net ecosystem CO2 exchange (NEE) during (i.e., resistance) and after (i.e., recovery) an experimental drought. The removal of PFTs caused a decrease of NEE, but the rate differed between microhabitats (i.e., hummocks and lawns) and the type of PFTs. Ericoid removal had a large effect on NEE in hummocks, while the graminoids played a major role in the lawns. The removal of PFTs did not affect the resistance or the recovery after the experimental drought. We argue that the response of Sphagnum mosses (the only PFT present in all treatments) to drought is dominant over that of coexisting PFTs. However, we observed that the moment in time when the system switched from C sink to C source during the drought was controlled by the vascular PFTs. In the light of climate change, the shifts in species composition or even the loss of certain PFTs are expected to strongly affect the future C dynamics in response to environmental stress. PMID:24649652

  13. Congruence of zebrin II expression and functional zones defined by climbing fiber topography in the flocculus.

    PubMed

    Pakan, J M P; Wylie, D R W

    2008-11-11

    The cerebellum is organized into parasagittal zones with respect to the topography of climbing fiber (CF) afferents and the expression of molecular markers such as zebrin II. Zebrin is expressed by a subset of Purkinje cells that are distributed as a parasagittal array of immunopositive and immunonegative stripes. Several studies in rodents suggest that, in general, CFs to the zebrin negative stripes convey somatosensory information, whereas CFs to the zebrin positive stripes convey information from visual and other sensory systems. The pigeon flocculus consists of four pairs of zebrin+/- stripes (P4 +/- through P7 +/-), however the CF input consists entirely of visual inputs. Thus, because the correspondence of zebrin expression and CF information must be different from that proposed for rodents, we investigated this relationship in the pigeon flocculus. Floccular Purkinje cells respond to patterns of optic flow resulting from self-rotation about one of two axes: either the vertical axis (zones 0 and 2), or a horizontal axis (zones 1 and 3). Visual CF afferents projecting to the flocculus arise from the medial column of the inferior olive (mcIO). Zones 0 and 2 receive input from the caudal mcIO, whereas zones 1 and 3 receive input from the rostral mcIO. We injected a fluorescent anterograde tracer into the rostral and/or caudal mcIO and visualized zebrin expression. There was a strict concordance between CF organization and zebrin labeling: caudal mcIO injections resulted in CFs in zebrin bands P4 +/- and P6 +/-, whereas rostral mcIO injections resulted in CFs in zebrin bands P5 +/- and P7 +/-. Thus, zebrin stripes P4 +/- and P6 +/- correspond to the vertical axis zones 0 and 2, whereas P5 +/- and P7 +/- correspond to the horizontal axis zones 1 and 3. This is the first explicit demonstration that a series of zebrin stripes corresponds with functional zones in the cerebellum. PMID:18824220

  14. Cross-dressing the virion: the transcapsidation of adeno-associated virus serotypes functionally defines subgroups.

    PubMed

    Rabinowitz, Joseph E; Bowles, Dawn E; Faust, Susan M; Ledford, Julie G; Cunningham, Scott E; Samulski, R Jude

    2004-05-01

    observed synergy: (i) heparin-mediated binding from AAV2 and (ii) an unidentified enhancement activity from AAV1 structural proteins. Using this procedure of mixing different AAV helper plasmids to generate "cross-dressed" AAV virions, we propose an additional means of classifying new AAV serotypes into subgroups based on functional approaches to analyze AAV capsid assembly, receptor-mediated binding, and virus trafficking. Exploitation of this approach in generating custom-designed AAV vectors should be of significant value to the field of gene therapy.

  15. Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli.

    PubMed

    Duffy, Darragh; Rouilly, Vincent; Libri, Valentina; Hasan, Milena; Beitz, Benoit; David, Mikael; Urrutia, Alejandra; Bisiaux, Aurélie; Labrie, Samuel T; Dubois, Annick; Boneca, Ivo G; Delval, Cécile; Thomas, Stéphanie; Rogge, Lars; Schmolz, Manfred; Quintana-Murci, Lluis; Albert, Matthew L

    2014-03-20

    Standardization of immunophenotyping procedures has become a high priority. We have developed a suite of whole-blood, syringe-based assay systems that can be used to reproducibly assess induced innate or adaptive immune responses. By eliminating preanalytical errors associated with immune monitoring, we have defined the protein signatures induced by (1) medically relevant bacteria, fungi, and viruses; (2) agonists specific for defined host sensors; (3) clinically employed cytokines; and (4) activators of T cell immunity. Our results provide an initial assessment of healthy donor reference values for induced cytokines and chemokines and we report the failure to release interleukin-1α as a common immunological phenotype. The observed naturally occurring variation of the immune response may help to explain differential susceptibility to disease or response to therapeutic intervention. The implementation of a general solution for assessment of functional immune responses will help support harmonization of clinical studies and data sharing.

  16. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins.

    PubMed

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  17. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins

    PubMed Central

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  18. Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate

    NASA Technical Reports Server (NTRS)

    Winters, T. A.; Russell, P. S.; Kohli, M.; Dar, M. E.; Neumann, R. D.; Jorgensen, T. J.

    1999-01-01

    Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

  19. Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

    PubMed

    Laha, Joydev K; Cuny, Gregory D

    2011-10-21

    Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields. PMID:21913645

  20. Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

    PubMed

    Laha, Joydev K; Cuny, Gregory D

    2011-10-21

    Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields.

  1. End-binding proteins and Ase1/PRC1 define local functionality of structurally distinct parts of the microtubule cytoskeleton.

    PubMed

    Duellberg, Christian; Fourniol, Franck J; Maurer, Sebastian P; Roostalu, Johanna; Surrey, Thomas

    2013-02-01

    The microtubule cytoskeleton is crucial for the intracellular organization of eukaryotic cells. It is a dynamic scaffold that has to perform a variety of very different functions. This multitasking is achieved through the activity of numerous microtubule-associated proteins. Two prominent classes of proteins are central to the selective recognition of distinct transiently existing structural features of the microtubule cytoskeleton. They define local functionality through tightly regulated protein recruitment. Here we summarize the recent developments in elucidating the molecular mechanism underlying the action of microtubule end-binding proteins (EBs) and antiparallel microtubule crosslinkers of the Ase1/PRC1 family that represent the core of these two recruitment modules. Despite their fundamentally different activities, these conserved families share several common features. PMID:23103209

  2. Improving DOE-2's RESYS routine: User defined functions to provide more accurate part load energy use and humidity predictions

    SciTech Connect

    Henderson, Hugh I.; Parker, Danny; Huang, Yu J.

    2000-08-04

    In hourly energy simulations, it is important to properly predict the performance of air conditioning systems over a range of full and part load operating conditions. An important component of these calculations is to properly consider the performance of the cycling air conditioner and how it interacts with the building. This paper presents improved approaches to properly account for the part load performance of residential and light commercial air conditioning systems in DOE-2. First, more accurate correlations are given to predict the degradation of system efficiency at part load conditions. In addition, a user-defined function for RESYS is developed that provides improved predictions of air conditioner sensible and latent capacity at part load conditions. The user function also provides more accurate predictions of space humidity by adding ''lumped'' moisture capacitance into the calculations. The improved cooling coil model and the addition of moisture capacitance predicts humidity swings that are more representative of the performance observed in real buildings.

  3. Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

    PubMed Central

    Lovelace, Erica S.; Polyak, Stephen J.

    2015-01-01

    Chronic viral infections like those caused by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA) and keeping HIV viral loads below detection with antiretroviral therapy (ART), there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK) and mechanistic target of rapamycin (mTOR), and these pathways directly influence cellular inflammatory status (such as NF-κB) and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function. PMID:26633463

  4. Association of tissue lineage and gene expression: conservatively and differentially expressed genes define common and special functions of tissues

    PubMed Central

    2010-01-01

    Background Embryogenesis is the process by which the embryo is formed, develops, and establishes developmental hierarchies of tissues. The recent advance in microarray technology made it possible to investigate the tissue specific patterns of gene expression and their relationship with tissue lineages. This study is focused on how tissue specific functions, tissue lineage, and cell differentiation are correlated, which is essential to understand embryonic development and organism complexity. Results We performed individual gene and gene set based analysis on multiple tissue expression data, in association with the classic topology of mammalian fate maps of embryogenesis. For each sub-group of tissues on the fate map, conservatively, differentially and correlatively expressed genes or gene sets were identified. Tissue distance was found to correlate with gene expression divergence. Tissues of the ectoderm or mesoderm origins from the same segments on the fate map shared more similar expression pattern than those from different origins. Conservatively expressed genes or gene sets define common functions in a tissue group and are related to tissue specific diseases, which is supported by results from Gene Ontology and KEGG pathway analysis. Gene expression divergence is larger in certain human tissues than in the mouse homologous tissues. Conclusion The results from tissue lineage and gene expression analysis indicate that common function features of neighbor tissue groups were defined by the conservatively expressed genes and were related to tissue specific diseases, and differentially expressed genes contribute to the functional divergence of tissues. The difference of gene expression divergence in human and mouse homologous tissues reflected the organism complexity, i.e. distinct neural development levels and different body sizes. PMID:21172044

  5. Defining an Abrasion Index for Lunar Surface Systems as a Function of Dust Interaction Modes and Variable Concentration Zones

    NASA Technical Reports Server (NTRS)

    Kobrick, Ryan L.; Klaus, David M.; Street, Kenneth W., Jr.

    2010-01-01

    Unexpected issues were encountered during the Apollo era of lunar exploration due to detrimental abrasion of materials upon exposure to the fine-grained, irregular shaped dust on the surface of the Moon. For critical design features involving contact with the lunar surface and for astronaut safety concerns, operational concepts and dust tolerance must be considered in the early phases of mission planning. To systematically define material selection criteria, dust interaction can be characterized by two-body or three-body abrasion testing, and subcategorically by physical interactions of compression, rolling, sliding and bending representing specific applications within the system. Two-body abrasion occurs when a single particle or asperity slides across a given surface removing or displacing material. Three-body abrasion occurs when multiple particles interact with a solid surface, or in between two surfaces, allowing the abrasives to freely rotate and interact with the material(s), leading to removal or displacement of mass. Different modes of interaction are described in this paper along with corresponding types of tests that can be utilized to evaluate each configuration. In addition to differential modes of abrasion, variable concentrations of dust in different zones can also be considered for a given system design and operational protocol. These zones include: (1) outside the habitat where extensive dust exposure occurs, (2) in a transitional zone such as an airlock or suitport, and (3) inside the habitat or spacesuit with a low particle count. These zones can be used to help define dust interaction frequencies, and corresponding risks to the systems and/or crew can be addressed by appropriate mitigation strategies. An abrasion index is introduced that includes the level of risk, R, the hardness of the mineralogy, H, the severity of the abrasion mode, S, and the frequency of particle interactions, F.

  6. Cross-study analysis of genomic data defines the ciliate multigenic epiplasmin family: strategies for functional analysis in Paramecium tetraurelia

    PubMed Central

    Damaj, Raghida; Pomel, Sébastien; Bricheux, Geneviève; Coffe, Gérard; Viguès, Bernard; Ravet, Viviane; Bouchard, Philippe

    2009-01-01

    Background The sub-membranous skeleton of the ciliate Paramecium, the epiplasm, is composed of hundreds of epiplasmic scales centered on basal bodies, and presents a complex set of proteins, epiplasmins, which belong to a multigenic family. The repeated duplications observed in the P. tetraurelia genome present an interesting model of the organization and evolution of a multigenic family within a single cell. Results To study this multigenic family, we used phylogenetic, structural, and analytical transcriptional approaches. The phylogenetic method defines 5 groups of epiplasmins in the multigenic family. A refined analysis by Hydrophobic Cluster Analysis (HCA) identifies structural characteristics of 51 epiplasmins, defining five separate groups, and three classes. Depending on the sequential arrangement of their structural domains, the epiplasmins are defined as symmetric, asymmetric or atypical. The EST data aid in this classification, in the identification of putative regulating sequences such as TATA or CAAT boxes. When specific RNAi experiments were conducted using sequences from either symmetric or asymmetric classes, phenotypes were drastic. Local effects show either disrupted or ill-shaped epiplasmic scales. In either case, this results in aborted cell division. Using structural features, we show that 4 epiplasmins are also present in another ciliate, Tetrahymena thermophila. Their affiliation with the distinctive structural groups of Paramecium epiplasmins demonstrates an interspecific multigenic family. Conclusion The epiplasmin multigenic family illustrates the history of genomic duplication in Paramecium. This study provides a framework which can guide functional analysis of epiplasmins, the major components of the membrane skeleton in ciliates. We show that this set of proteins handles an important developmental information in Paramecium since maintenance of epiplasm organization is crucial for cell morphogenesis. PMID:19493334

  7. Surface-Directed Assembly of Sequence-Defined Synthetic Polymers into Networks of Hexagonally Patterned Nanoribbons with Controlled Functionalities.

    PubMed

    Chen, Chun-Long; Zuckermann, Ronald N; DeYoreo, James J

    2016-05-24

    The exquisite self-assembly of proteins and peptides in nature into highly ordered functional materials has inspired innovative approaches to the design and synthesis of biomimetic materials. While sequence-defined polymers hold great promise to mimic proteins and peptides for functions, controlled assembly of them on surfaces still remains underdeveloped. Here, we report the assembly of 12-mer peptoids containing alternating acidic and aromatic monomers into networks of hexagonally patterned nanoribbons on mica surfaces. Ca(2+)-carboxylate coordination creates peptoid-peptoid and peptoid-mica interactions that control self-assembly. In situ atomic force microscopy (AFM) shows that peptoids first assemble into discrete nanoparticles; these particles then transform into hexagonally patterned nanoribbons on mica surfaces. AFM-based dynamic force spectroscopy studies show that peptoid-mica interactions are much stronger than peptoid-peptoid interactions, illuminating the driving forces for mica-directed peptoid assembly. We further demonstrate the display of functional domains at the N-terminus of assembling peptoids to produce extended networks with similar hierarchical structures. This research demonstrates that surface-directed peptoid assembly can be used as a robust platform to develop biomimetic coating materials for applications. PMID:27136277

  8. Skeletal muscle mass adjusted by height correlated better with muscular functions than that adjusted by body weight in defining sarcopenia.

    PubMed

    Han, Der-Sheng; Chang, Ke-Vin; Li, Chia-Ming; Lin, Yu-Hong; Kao, Tung-Wei; Tsai, Keh-Sung; Wang, Tyng-Grey; Yang, Wei-Shiung

    2016-01-20

    Sarcopenia, characterized by low muscle mass and function, results in frailty, comorbidities and mortality. However, its prevalence varies according to the different criteria used in its diagnosis. This cross-sectional study investigated the difference in the number of sarcopenia cases recorded by two different measurement methods of low muscle mass to determine which measurement was better. We recruited 878 (54.2% female) individuals aged over 65 years and obtained their body composition and functional parameters. Low muscle mass was defined as two standard deviations below either the mean height-adjusted (hSMI) or weight-adjusted (wSMI) muscle mass of a young reference group. The prevalence of sarcopenia was 6.7% vs. 0.4% (male/female) by hSMI, and 4.0% vs. 10.7% (male/female) by wSMI. The κ coefficients for these two criteria were 0.39 vs. 0.03 (male/female), and 0.17 in all subjects. Serum myostatin levels correlated positively with gait speed (r = 0.142, p = 0.007) after adjustment for gender. hSMI correlated with grip strength, cardiopulmonary endurance, leg endurance, gait speed, and flexibility. wSMI correlated with grip strength, leg endurance, gait speed, and flexibility. Since hSMI correlated more closely with grip strength and more muscular functions, we recommend hSMI in the diagnosis of low muscle mass.

  9. Bulk regional viral injection in neonatal mice enables structural and functional interrogation of defined neuronal populations throughout targeted brain areas.

    PubMed

    Cheetham, Claire E J; Grier, Bryce D; Belluscio, Leonardo

    2015-01-01

    The ability to label and manipulate specific cell types is central to understanding the structure and function of neuronal circuits. Here, we have developed a simple, affordable strategy for labeling of genetically defined populations of neurons throughout a targeted brain region: Bulk Regional Viral Injection (BReVI). Our strategy involves a large volume adeno-associated virus (AAV) injection in the targeted brain region of neonatal Cre driver mice. Using the mouse olfactory bulb (OB) as a model system, we tested the ability of BReVI to broadly and selectively label tufted cells, one of the two principal neuron populations of the OB, in CCK-IRES-Cre mice. BReVI resulted in labeling of neurons throughout the injected OB, with no spatial bias toward the injection site and no evidence of damage. The specificity of BReVI labeling was strikingly similar to that seen previously using immunohistochemical staining for cholecystokinin (CCK), an established tufted cell marker. Hence, the CCK-IRES-Cre line in combination with BReVI can provide an important tool for targeting and manipulation of OB tufted cells. We also found robust Cre-dependent reporter expression within three days of BReVI, which enabled us to assess developmental changes in the number and laminar distribution of OB tufted cells during the first three postnatal weeks. Furthermore, we demonstrate that BReVI permits structural and functional imaging in vivo, and can be combined with transgenic strategies to facilitate multi-color labeling of neuronal circuit components. BReVI is broadly applicable to different Cre driver lines and can be used to regionally manipulate genetically defined populations of neurons in any accessible brain region. PMID:26594154

  10. Bulk regional viral injection in neonatal mice enables structural and functional interrogation of defined neuronal populations throughout targeted brain areas

    PubMed Central

    Cheetham, Claire E. J.; Grier, Bryce D.; Belluscio, Leonardo

    2015-01-01

    The ability to label and manipulate specific cell types is central to understanding the structure and function of neuronal circuits. Here, we have developed a simple, affordable strategy for labeling of genetically defined populations of neurons throughout a targeted brain region: Bulk Regional Viral Injection (BReVI). Our strategy involves a large volume adeno-associated virus (AAV) injection in the targeted brain region of neonatal Cre driver mice. Using the mouse olfactory bulb (OB) as a model system, we tested the ability of BReVI to broadly and selectively label tufted cells, one of the two principal neuron populations of the OB, in CCK-IRES-Cre mice. BReVI resulted in labeling of neurons throughout the injected OB, with no spatial bias toward the injection site and no evidence of damage. The specificity of BReVI labeling was strikingly similar to that seen previously using immunohistochemical staining for cholecystokinin (CCK), an established tufted cell marker. Hence, the CCK-IRES-Cre line in combination with BReVI can provide an important tool for targeting and manipulation of OB tufted cells. We also found robust Cre-dependent reporter expression within three days of BReVI, which enabled us to assess developmental changes in the number and laminar distribution of OB tufted cells during the first three postnatal weeks. Furthermore, we demonstrate that BReVI permits structural and functional imaging in vivo, and can be combined with transgenic strategies to facilitate multi-color labeling of neuronal circuit components. BReVI is broadly applicable to different Cre driver lines and can be used to regionally manipulate genetically defined populations of neurons in any accessible brain region. PMID:26594154

  11. Integrated Utility Function-Based Scheduling for Mixed Traffic in LTE Systems

    NASA Astrophysics Data System (ADS)

    Lee, Deokhui; So, Jaewoo

    This paper proposes a utility function-based scheduling algorithm for integrated real-time and non-real-time services in long-term evolution systems. The proposed utility function satisfies the target dropping ratio of real-time users; it uses the delay constraint and increases the throughput of non-real-time users by scheduling real-time users together with non-real-time users. Simulation results show that the proposed scheduling algorithm significantly improves the throughput of non-real-time users without sacrificing the quality of service of real-time users.

  12. Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection.

    PubMed

    Otsuki, Akihito; Suzuki, Mikiko; Katsuoka, Fumiki; Tsuchida, Kouhei; Suda, Hiromi; Morita, Masanobu; Shimizu, Ritsuko; Yamamoto, Masayuki

    2016-02-01

    Nrf2-small Maf (sMaf) heterodimer is essential for the inducible expression of cytoprotective genes upon exposure to oxidative and xenobiotic stresses. While the Nrf2-sMaf heterodimer recognizes DNA sequences referred to as the antioxidant/electrophile responsive element (ARE/EpRE), we here define these DNA sequences collectively as CNC-sMaf binding element (CsMBE). In contrast, large and small Maf proteins are able to form homodimers that recognize the Maf recognition element (MARE). CsMBE and MARE share a conserved core sequence but they differ in the 5'-adjacent nucleotide neighboring the core. Because of the high similarity between the CsMBE and MARE sequences, it has been unclear how many target binding sites and target genes are shared by the Nrf2-sMaf heterodimers and Maf homodimers. To address this issue, we introduced a substitution mutation of alanine to tyrosine at position 502 in Nrf2, which rendered the DNA-binding domain structure of Nrf2 similar to Maf, and generated knock-in mice expressing the Nrf2(A502Y) mutant. Our chromatin immunoprecipitation-sequencing analyses showed that binding sites of Nrf2(A502Y)-sMaf were dramatically changed from CsMBE to MARE in vivo. Intriguingly, however, one-quarter of the Nrf2(A502Y)-sMaf binding sites also bound Nrf2-sMaf commonly and vice versa. RNA-sequencing analyses revealed that Nrf2(A502Y)-sMaf failed to induce expression of major cytoprotective genes upon stress stimulation, which increased the sensitivity of Nrf2(A502Y) mutant mice to acute acetaminophen toxicity. These results demonstrate that the unique cistrome defined as CsMBE is strictly required for the Nrf2-sMaf heterodimer function in cytoprotection and that the roles played by CsMBE differ sharply from those of MARE. PMID:26677805

  13. High-Functioning Autism and Asperger's Disorder: Utility and Meaning for Families

    ERIC Educational Resources Information Center

    Ruiz Calzada, Luisa; Pistrang, Nancy; Mandy, William P. L.

    2012-01-01

    We used framework analysis to investigate the utility of pervasive developmental disorder diagnoses, interviewing young people (aged 9-16 years) with high-functioning autistic disorder (AD) and Asperger's disorder (AsD), and their parents. Twenty two participants from ten families described both gains and costs resulting from diagnosis. Perceived…

  14. Utility functions and resource management in an oversubscribed heterogeneous computing environment

    DOE PAGES

    Khemka, Bhavesh; Friese, Ryan; Briceno, Luis Diego; Siegel, Howard Jay; Maciejewski, Anthony A.; Koenig, Gregory A.; Groer, Christopher S.; Hilton, Marcia M.; Poole, Stephen W.; Okonski, G.; et al

    2014-09-26

    We model an oversubscribed heterogeneous computing system where tasks arrive dynamically and a scheduler maps the tasks to machines for execution. The environment and workloads are based on those being investigated by the Extreme Scale Systems Center at Oak Ridge National Laboratory. Utility functions that are designed based on specifications from the system owner and users are used to create a metric for the performance of resource allocation heuristics. Each task has a time-varying utility (importance) that the enterprise will earn based on when the task successfully completes execution. We design multiple heuristics, which include a technique to drop lowmore » utility-earning tasks, to maximize the total utility that can be earned by completing tasks. The heuristics are evaluated using simulation experiments with two levels of oversubscription. The results show the benefit of having fast heuristics that account for the importance of a task and the heterogeneity of the environment when making allocation decisions in an oversubscribed environment. Furthermore, the ability to drop low utility-earning tasks allow the heuristics to tolerate the high oversubscription as well as earn significant utility.« less

  15. Utility functions and resource management in an oversubscribed heterogeneous computing environment

    SciTech Connect

    Khemka, Bhavesh; Friese, Ryan; Briceno, Luis Diego; Siegel, Howard Jay; Maciejewski, Anthony A.; Koenig, Gregory A.; Groer, Christopher S.; Hilton, Marcia M.; Poole, Stephen W.; Okonski, G.; Rambharos, R.

    2014-09-26

    We model an oversubscribed heterogeneous computing system where tasks arrive dynamically and a scheduler maps the tasks to machines for execution. The environment and workloads are based on those being investigated by the Extreme Scale Systems Center at Oak Ridge National Laboratory. Utility functions that are designed based on specifications from the system owner and users are used to create a metric for the performance of resource allocation heuristics. Each task has a time-varying utility (importance) that the enterprise will earn based on when the task successfully completes execution. We design multiple heuristics, which include a technique to drop low utility-earning tasks, to maximize the total utility that can be earned by completing tasks. The heuristics are evaluated using simulation experiments with two levels of oversubscription. The results show the benefit of having fast heuristics that account for the importance of a task and the heterogeneity of the environment when making allocation decisions in an oversubscribed environment. Furthermore, the ability to drop low utility-earning tasks allow the heuristics to tolerate the high oversubscription as well as earn significant utility.

  16. Time Utility Functions for Modeling and Evaluating Resource Allocations in a Heterogeneous Computing System

    SciTech Connect

    Briceno, Luis Diego; Khemka, Bhavesh; Siegel, Howard Jay; Maciejewski, Anthony A; Groer, Christopher S; Koenig, Gregory A; Okonski, Gene D; Poole, Stephen W

    2011-01-01

    This study considers a heterogeneous computing system and corresponding workload being investigated by the Extreme Scale Systems Center (ESSC) at Oak Ridge National Laboratory (ORNL). The ESSC is part of a collaborative effort between the Department of Energy (DOE) and the Department of Defense (DoD) to deliver research, tools, software, and technologies that can be integrated, deployed, and used in both DOE and DoD environments. The heterogeneous system and workload described here are representative of a prototypical computing environment being studied as part of this collaboration. Each task can exhibit a time-varying importance or utility to the overall enterprise. In this system, an arriving task has an associated priority and precedence. The priority is used to describe the importance of a task, and precedence is used to describe how soon the task must be executed. These two metrics are combined to create a utility function curve that indicates how valuable it is for the system to complete a task at any given moment. This research focuses on using time-utility functions to generate a metric that can be used to compare the performance of different resource schedulers in a heterogeneous computing system. The contributions of this paper are: (a) a mathematical model of a heterogeneous computing system where tasks arrive dynamically and need to be assigned based on their priority, precedence, utility characteristic class, and task execution type, (b) the use of priority and precedence to generate time-utility functions that describe the value a task has at any given time, (c) the derivation of a metric based on the total utility gained from completing tasks to measure the performance of the computing environment, and (d) a comparison of the performance of resource allocation heuristics in this environment.

  17. Defining the Essential Function of Yeast Hsf1 Reveals a Compact Transcriptional Program for Maintaining Eukaryotic Proteostasis.

    PubMed

    Solís, Eric J; Pandey, Jai P; Zheng, Xu; Jin, Dexter X; Gupta, Piyush B; Airoldi, Edoardo M; Pincus, David; Denic, Vladimir

    2016-07-01

    Despite its eponymous association with the heat shock response, yeast heat shock factor 1 (Hsf1) is essential even at low temperatures. Here we show that engineered nuclear export of Hsf1 results in cytotoxicity associated with massive protein aggregation. Genome-wide analysis revealed that Hsf1 nuclear export immediately decreased basal transcription and mRNA expression of 18 genes, which predominately encode chaperones. Strikingly, rescuing basal expression of Hsp70 and Hsp90 chaperones enabled robust cell growth in the complete absence of Hsf1. With the exception of chaperone gene induction, the vast majority of the heat shock response was Hsf1 independent. By comparative analysis of mammalian cell lines, we found that only heat shock-induced but not basal expression of chaperones is dependent on the mammalian Hsf1 homolog (HSF1). Our work reveals that yeast chaperone gene expression is an essential housekeeping mechanism and provides a roadmap for defining the function of HSF1 as a driver of oncogenesis. PMID:27320198

  18. The association between functional disability and acute care utilization among the elderly in Taiwan.

    PubMed

    Wu, Chen-Yi; Hu, Hsiao-Yun; Li, Chung-Pin; Fang, Yi-Ting; Huang, Nicole; Chou, Yiing-Jeng

    2013-01-01

    Disability is associated with increased long-term care use among the elderly, but its association with utilization of acute care is not well understood. The aim of this study is to investigate the association between functional disability and acute medical care utilization among the elderly. This nationwide, population-based cohort study was based on data from the 2005 National Health Interview Survey (NHIS), linking to the 2004-2007 National Health Insurance (NHI) claims data. A total of 1521 elderly subjects aged 65 years or above were observed from the year 2004 to 2006; this sample was considered to be a national representative sample. The utilization of acute medical care (including outpatient services, emergency services, and inpatient services) and medical expenditure were measured. Functional disability was measured by determining limitations on activities of daily living (ADLs), instrumental activities of daily living (IADLs), and mobility. After adjusting for age, comorbidity, and sociodemographic characteristics, functional disability that affected IADLs or mobility was a significant factor contributing to the increased use of care. A clear proportional relationship existed between disability and utilization, and this pattern persisted across different types of acute care services. Disability affecting IADLs or mobility, rather than ADLs, was a more sensitive predictor of acute medical care utilization. Compared to elderly persons with no limitations, the medical expenditure of those with moderate-to-severe limitations was 2-3 times higher for outpatient, emergency, and inpatient services. In conclusion, functional disability among the elderly is a significant factor contributing to the increased use of acute care services.

  19. Analysis of C. elegans NR2E nuclear receptors defines three conserved clades and ligand-independent functions

    PubMed Central

    2012-01-01

    Background The nuclear receptors (NRs) are an important class of transcription factors that are conserved across animal phyla. Canonical NRs consist of a DNA-binding domain (DBD) and ligand-binding domain (LBD). While most animals have 20–40 NRs, nematodes of the genus Caenorhabditis have experienced a spectacular proliferation and divergence of NR genes. The LBDs of evolutionarily-conserved Caenorhabditis NRs have diverged sharply from their Drosophila and vertebrate orthologs, while the DBDs have been strongly conserved. The NR2E family of NRs play critical roles in development, especially in the nervous system. In this study, we explore the phylogenetics and function of the NR2E family of Caenorhabditis elegans, using an in vivo assay to test LBD function. Results Phylogenetic analysis reveals that the NR2E family of NRs consists of three broadly-conserved clades of orthologous NRs. In C. elegans, these clades are defined by nhr-67, fax-1 and nhr-239. The vertebrate orthologs of nhr-67 and fax-1 are Tlx and PNR, respectively. While the nhr-239 clade includes orthologs in insects (Hr83), an echinoderm, and a hemichordate, the gene appears to have been lost from vertebrate lineages. The C. elegans and C. briggsae nhr-239 genes have an apparently-truncated and highly-diverged LBD region. An additional C. elegans NR2E gene, nhr-111, appears to be a recently-evolved paralog of fax-1; it is present in C. elegans, but not C. briggsae or other animals with completely-sequenced genomes. Analysis of the relatively unstudied nhr-111 and nhr-239 genes demonstrates that they are both expressed—nhr-111 very broadly and nhr-239 in a small subset of neurons. Analysis of the FAX-1 LBD in an in vivo assay revealed that it is not required for at least some developmental functions. Conclusions Our analysis supports three conserved clades of NR2E receptors, only two of which are represented in vertebrates, indicating three ancestral NR2E genes in the urbilateria. The lack of a

  20. Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation.

    PubMed

    Das, Sreetama; Ramakumar, Suryanarayanarao; Pal, Debnath

    2014-12-01

    Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve > 0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

  1. Investigation of the functional role of aldose 1-epimerase in engineered cellobiose utilization.

    PubMed

    Li, Sijin; Ha, Suk-Jin; Kim, Hee Jin; Galazka, Jonathan M; Cate, Jamie H D; Jin, Yong-Su; Zhao, Huimin

    2013-10-10

    Functional expression of a cellodextrin transporter and an intracellular β-glucosidase from Neurospora crassa in Saccharomyces cerevisiae enables simultaneous co-fermentation of cellobiose and non-glucose sugars such as xylose. Here we investigate the functional role of aldose 1-epimerase (AEP) in engineered cellobiose utilization. One AEP (Gal10) and two putative AEPs (Yhr210c and Ynr071c sharing 50.6% and 51.0% amino acid identity with Gal10, respectively) were selected. Deletion of GAL10 led to complete loss of both AEP activity and cell growth on cellobiose, while GAL10 complementation restored the AEP activity and cell growth. In addition, deletion of YHR210C or YNR071C resulted in improved cellobiose utilization. These results suggest that the intracellular mutarotation of β-glucose to α-glucose might be a rate controlling step and Gal10 play a crucial role in cellobiose fermentation by engineered S. cerevisiae. PMID:23954547

  2. Feasibility and reliability of a mailed questionnaire to obtain visual analogue scale valuations for health states defined by the Health Utilities Index Mark 3.

    PubMed

    Raat, Hein; Bonsel, Gouke J; Hoogeveen, W Christina; Essink-Bot, Marie-Louise

    2004-01-01

    To establish the generalizability (external validity) of the Health Utilities Index Mark 3 (HUI3) as a single-summary score generic outcome measure in numerous countries/subgroups (including children), repeated studies of community preferences should be performed in various settings. In performing multiple HUI3 studies, a mailed questionnaire approach, if feasible and reliable, might be substituted for oral interviews. In the present study, we assessed the feasibility and reliability of a mailed questionnaire approach originally developed for the EQ-5D, for the purpose of collecting Visual Analogue Scale (VAS) valuations from parents as surrogate responders for 65 pediatric HUI3 health states and for the state of being dead. Untransformed mean VAS scores of the health states and scores converted into preliminary Standard Gamble (SG)-utilities were compared with Canadian and French multiattribute utility estimates. A random sample of 1920 parents of schoolchildren (aged 4 to 13) received a mailed questionnaire. Each parent was asked to rate 6 HUI3 health states on a 0 to 100 VAS. Response was 70%. Mean completion time was 20 minutes (SD 9). The questionnaire was rated difficult by only 9%. The current format was, however, inappropriate for valuing the state of being dead. Interrater reliability of health state valuations was.87. Spearman's rank correlations, Pearson-R correlations and intra class correlation coefficients (ICCs) between untransformed VAS valuations and Canadian/French utility estimates were > or =.87. However, preliminary SG-utilities showed diminished ICCs (.71 to.72). The data support the feasibility and reliability of mailed HUI3 valuation questionnaires to a considerable extent, but further methodological studies regarding other formats and different populations are recommended.

  3. Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

    PubMed Central

    Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

    2014-01-01

    Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

  4. The Utility of Forms and Functions of Aggression in Emerging Adulthood: Association with Personality Disorder Symptomatology

    ERIC Educational Resources Information Center

    Ostrov, Jamie M.; Houston, Rebecca J.

    2008-01-01

    A sample of 679 (341 women) emerging adults (M = 18.90 years; SD = 1.11; range = 18.00-22.92) participated in a study on the utility of forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggression. We examined the link between these four subtypes of aggression and personality pathology (i.e., psychopathic…

  5. Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease.

    PubMed

    Liu, Joanne J; Green, Pnina; John Mann, J; Rapoport, Stanley I; Sublette, M Elizabeth

    2015-02-01

    Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer's disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease.

  6. Comparative evaluation of mathematical functions to describe growth and efficiency of phosphorus utilization in growing pigs.

    PubMed

    Kebreab, E; Schulin-Zeuthen, M; Lopez, S; Soler, J; Dias, R S; de Lange, C F M; France, J

    2007-10-01

    Success of pig production depends on maximizing return over feed costs and addressing potential nutrient pollution to the environment. Mathematical modeling has been used to describe many important aspects of inputs and outputs of pork production. This study was undertaken to compare 4 mathematical functions for the best fit in terms of describing specific data sets on pig growth and, in a separate experiment, to compare these 4 functions for describing of P utilization for growth. Two data sets with growth data were used to conduct growth analysis and another data set was used for P efficiency analysis. All data sets were constructed from independent trials that measured BW, age, and intake. Four growth functions representing diminishing returns (monomolecular), sigmoidal with a fixed point of inflection (Gompertz), and sigmoidal with a variable point of inflection (Richards and von Bertalanffy) were used. Meta-analysis of the data was conducted to identify the most appropriate functions for growth and P utilization. Based on Bayesian information criteria, the Richards equation described the BW vs. age data best. The additional parameter of the Richards equation was necessary because the data required a lower point of inflection (138 d) than the Gompertz, with a fixed point of inflexion at 1/e times the final BW (189 d), could accommodate. Lack of flexibility in the Gompertz equation was a limitation to accurate prediction. The monomolecular equation was best at determining efficiencies of P utilization for BW gain compared with the sigmoidal functions. The parameter estimate for the rate constant in all functions decreased as available P intake increased. Average efficiencies during different stages of growth were calculated and offer insight into targeting stages where high feed (nutrient) input is required and when adjustments are needed to accommodate the loss of efficiency and the reduction of potential pollution problems. It is recommended that the Richards

  7. Metatranscriptomic and functional metagenomic analysis of methylphosphonate utilization by marine bacteria

    PubMed Central

    Martínez, Asunción; Ventouras, Laure-Anne; Wilson, Samuel T.; Karl, David M.; DeLong, Edward F.

    2013-01-01

    Aerobic degradation of methylphosphonate (MPn) by marine bacterioplankton has been hypothesized to contribute significantly to the ocean's methane supersaturation, yet little is known about MPn utilization by marine microbes. To identify the microbial taxa and metabolic functions associated with MPn-driven methane production we performed parallel metagenomic, metatranscriptomic, and functional screening of microcosm perturbation experiments using surface water collected in the North Pacific Subtropical Gyre. In nutrient amended microcosms containing MPn, a substrate-driven microbial succession occurred. Initially, the addition of glucose and nitrate resulted in a bloom of Vibrionales and a transcriptional profile dominated by glucose-specific PTS transport and polyhydroxyalkanoate biosynthesis. Transcripts associated with phosphorus (P) acquisition were also overrepresented and suggested that the addition of glucose and nitrate had driven the community to P depletion. At this point, a second community shift occurred characterized by the increase in C-P lyase containing microbes of the Vibrionales and Rhodobacterales orders. Transcripts associated with C-P lyase components were among the most highly expressed at the community level, and only C-P lyase clusters were recovered in a functional screen for MPn utilization, consistent with this pathway being responsible for the majority, if not all, of the methane accumulation we observed. Our results identify specific bacterioplankton taxa that can utilize MPn aerobically under conditions of P limitation using the C-P lyase pathway, and thereby elicit a significant increase in the dissolved methane concentration. PMID:24324460

  8. Metatranscriptomic and functional metagenomic analysis of methylphosphonate utilization by marine bacteria.

    PubMed

    Martínez, Asunción; Ventouras, Laure-Anne; Wilson, Samuel T; Karl, David M; Delong, Edward F

    2013-01-01

    Aerobic degradation of methylphosphonate (MPn) by marine bacterioplankton has been hypothesized to contribute significantly to the ocean's methane supersaturation, yet little is known about MPn utilization by marine microbes. To identify the microbial taxa and metabolic functions associated with MPn-driven methane production we performed parallel metagenomic, metatranscriptomic, and functional screening of microcosm perturbation experiments using surface water collected in the North Pacific Subtropical Gyre. In nutrient amended microcosms containing MPn, a substrate-driven microbial succession occurred. Initially, the addition of glucose and nitrate resulted in a bloom of Vibrionales and a transcriptional profile dominated by glucose-specific PTS transport and polyhydroxyalkanoate biosynthesis. Transcripts associated with phosphorus (P) acquisition were also overrepresented and suggested that the addition of glucose and nitrate had driven the community to P depletion. At this point, a second community shift occurred characterized by the increase in C-P lyase containing microbes of the Vibrionales and Rhodobacterales orders. Transcripts associated with C-P lyase components were among the most highly expressed at the community level, and only C-P lyase clusters were recovered in a functional screen for MPn utilization, consistent with this pathway being responsible for the majority, if not all, of the methane accumulation we observed. Our results identify specific bacterioplankton taxa that can utilize MPn aerobically under conditions of P limitation using the C-P lyase pathway, and thereby elicit a significant increase in the dissolved methane concentration. PMID:24324460

  9. Utility of Functional Hemodynamics and Echocardiography to Aid Diagnosis and Management of Shock.

    PubMed

    McGee, William T; Raghunathan, Karthik; Adler, Adam C

    2015-12-01

    The utility of functional hemodynamics and bedside ultrasonography is increasingly recognized as advantageous for both improved diagnosis and management of shock states. In contrast to conventional "static" measures, "dynamic" hemodynamic measures and bedside imaging modalities enhance pathophysiology-based comprehensive understanding of shock states and the response to therapy. The current editions of major textbooks in the primary specialties--in which clinicians routinely encounter patients in shock--including surgery, anesthesia, emergency medicine, and internal medicine continue to incorporate traditional (conventional) descriptions of shock that use well-described (but potentially misleading) intravascular pressures to classify shock states. Reliance on such intravascular pressure measurements is not as helpful as newer "dynamic" functional measures including ultrasonography to both better assess volume responsiveness and biventricular cardiac function. This review thus emphasizes the application of current functional hemodynamics and ultrasonography to the diagnosis and management of shock as a contrast to conventional "static" pressure-based measures.

  10. When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving.

    PubMed

    Drury, Stacy S; Sánchez, Mar M; Gonzalez, Andrea

    2016-01-01

    This article is part of a Special Issue "Parental Care".Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for "optimal" caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. PMID:26506032

  11. Microbial resource utilization traits and trade-offs: implications for community structure, functioning, and biogeochemical impacts at present and in the future

    PubMed Central

    Litchman, Elena; Edwards, Kyle F.; Klausmeier, Christopher A.

    2015-01-01

    Trait-based approaches provide a mechanistic framework to understand and predict the structure and functioning of microbial communities. Resource utilization traits and trade-offs are among key microbial traits that describe population dynamics and competition among microbes. Several important trade-offs have been identified for prokaryotic and eukaryotic microbial taxa that define contrasting ecological strategies and contribute to species coexistence and diversity. The shape, dimensionality, and hierarchy of trade-offs may determine coexistence patterns and need to be better characterized. Laboratory measured resource utilization traits can be used to explain temporal and spatial structure and dynamics of natural microbial communities and predict biogeochemical impacts. Global environmental change can alter microbial community composition through altering resource utilization by different microbes and, consequently, may modify biogeochemical impacts of microbes. PMID:25904900

  12. Evaluation of a BED-SIDE platelet function assay: performance and clinical utility.

    PubMed

    Lau, Wei C; Walker, C Ty; Obilby, David; Wash, Mark M; Carville, David G M; Guyer, Kirk E; Bates, Eric R

    2002-01-01

    Platelets have a pivotal role in the initial defense against insult to the vasculature and are also recognized of critical importance in the acute care settings of percutaneous coronary intervention and cardiopulmonary bypass. In these environments both platelet count and function may be markedly compromised. Unfortunately, current assays to evaluate the parameters of platelet count and function are of limited utility for bed-side testing. Moreover, it is suggested that there may be significant inter patient variation in response to antiplatelet therapy that may be exacerbated by other agents (e.g. heparin) that are routinely administered during cardiac intervention. Here we describe a practical, rapid and user-friendly whole blood platelet function assay that has been developed for use in bed-side settings. Platelet agonists were formulated with an anticoagulant and lyophilized in blood collection tubes standardised to receive a l mL fresh whole blood sample. In the presence of an agonist, platelets are activated and interact (aggregate). Using traditional cell counting principles, non-aggregated platelets are counted whereas aggregated platelets are not. The percentage (%) of functional platelets in reference to a baseline tube may then be determined. Results are available within four minutes. Platelet aggregation in whole blood demonstrated good correlation with turbidometric aggregometry for both ADP (r=0.91) and collagen (r=0.88). Moreover, in clinical settings where antiplatelet agents were administered, this rapid, bed-side, platelet function assay demonstrated utility in monitoring patient response to these therapies. This novel bed-side assay of platelet function is extremely suitable for the clinical environment with a rapid turn-around time. In addition, it provides a full haematology profile, including platelet count, and should permit enhancement of transfusion and interventional decisions. PMID:17890800

  13. On-line optical and X-ray spectroscopies with crystallography: an integrated approach for determining metalloprotein structures in functionally well defined states.

    PubMed

    Ellis, Mark J; Buffey, Steven G; Hough, Michael A; Hasnain, S Samar

    2008-09-01

    X-ray-induced redox changes can lead to incorrect assignments of the functional states of metals in metalloprotein crystals. The need for on-line monitoring of the status of metal ions (and other chromophores) during protein crystallography experiments is of growing importance with the use of intense synchrotron X-ray beams. Significant efforts are therefore being made worldwide to combine different spectroscopies in parallel with X-ray crystallographic data collection. Here the implementation and utilization of optical and X-ray absorption spectroscopies on the modern macromolecular crystallography (MX) beamline 10, at the SRS, Daresbury Laboratory, is described. This beamline is equipped with a dedicated monolithic energy-dispersive X-ray fluorescence detector, allowing X-ray absorption spectroscopy (XAS) measurements to be made in situ on the same crystal used to record the diffraction data. In addition, an optical microspectrophotometer has been incorporated on the beamline, thus facilitating combined MX, XAS and optical spectroscopic measurements. By uniting these techniques it is also possible to monitor the status of optically active and optically silent metal centres present in a crystal at the same time. This unique capability has been applied to observe the results of crystallographic data collection on crystals of nitrite reductase from Alcaligenes xylosoxidans, which contains both type-1 and type-2 Cu centres. It is found that the type-1 Cu centre photoreduces quickly, resulting in the loss of the 595 nm peak in the optical spectrum, while the type-2 Cu centre remains in the oxidized state over a much longer time period, for which independent confirmation is provided by XAS data as this centre has an optical spectrum which is barely detectable using microspectrophotometry. This example clearly demonstrates the importance of using two on-line methods, spectroscopy and XAS, for identifying well defined redox states of metalloproteins during

  14. Vorschlag zur Erarbeitung einer operationalen Fremdwortdefinition (A Proposal for Establishing a Functional System for Defining Foreign Words)

    ERIC Educational Resources Information Center

    Schank, Gerd

    1974-01-01

    In order to define words borrowed from other languages, dialects or varieties within a dialect, a synchronic definition, including the degree of integration into the borrowing language, is more useful and flexible than the traditional etymological approach. (Text is in German.) (TL)

  15. Defining "Development".

    PubMed

    Pradeu, Thomas; Laplane, Lucie; Prévot, Karine; Hoquet, Thierry; Reynaud, Valentine; Fusco, Giuseppe; Minelli, Alessandro; Orgogozo, Virginie; Vervoort, Michel

    2016-01-01

    Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory.

  16. Optimization of the dressing parameters in cylindrical grinding based on a generalized utility function

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Irina

    2016-01-01

    The existing studies, concerning the dressing process, focus on the major influence of the dressing conditions on the grinding response variables. However, the choice of the dressing conditions is often made, based on the experience of the qualified staff or using data from reference books. The optimal dressing parameters, which are only valid for the particular methods and dressing and grinding conditions, are also used. The paper presents a methodology for optimization of the dressing parameters in cylindrical grinding. The generalized utility function has been chosen as an optimization parameter. It is a complex indicator determining the economic, dynamic and manufacturing characteristics of the grinding process. The developed methodology is implemented for the dressing of aluminium oxide grinding wheels by using experimental diamond roller dressers with different grit sizes made of medium- and high-strength synthetic diamonds type ??32 and ??80. To solve the optimization problem, a model of the generalized utility function is created which reflects the complex impact of dressing parameters. The model is built based on the results from the conducted complex study and modeling of the grinding wheel lifetime, cutting ability, production rate and cutting forces during grinding. They are closely related to the dressing conditions (dressing speed ratio, radial in-feed of the diamond roller dresser and dress-out time), the diamond roller dresser grit size/grinding wheel grit size ratio, the type of synthetic diamonds and the direction of dressing. Some dressing parameters are determined for which the generalized utility function has a maximum and which guarantee an optimum combination of the following: the lifetime and cutting ability of the abrasive wheels, the tangential cutting force magnitude and the production rate of the grinding process. The results obtained prove the possibility of control and optimization of grinding by selecting particular dressing

  17. Organization of Artificial Superlattices Utilizing Nanosheets as a Building Block and Exploration of Their Advanced Functions

    NASA Astrophysics Data System (ADS)

    Ma, Renzhi; Sasaki, Takayoshi

    2015-07-01

    This review covers some of the latest developments in the organization of artificial superlattice assemblies utilizing colloidal oxide or hydroxide nanosheets bearing a negative or positive charge, respectively. Various solution-based procedures, e.g., flocculation, electrostatic sequential adsorption, and Langmuir-Blodgett deposition, have been introduced for the self-assembly of 2D nanosheets. Superlattice composites or films integrated with different nanosheets may yield concerted or synergistic modulation, e.g., soft coupling or new electronic states at interfaces. This behavior offers an unprecedented opportunity for the exploration of high-performance devices, as well as advanced or novel functions that cannot be achieved with a single-component material.

  18. Defining Infertility

    MedlinePlus

    ... of the American Society for Reproductive Medicine Defining infertility What is infertility? Infertility is “the inability to conceive after 12 months ... to conceive after 6 months is generally considered infertility. How common is it? Infertility affects 10%-15% ...

  19. Utilization of functional near infrared spectroscopy for non-invasive evaluation

    NASA Astrophysics Data System (ADS)

    Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

    2016-07-01

    The goal of this brief review is to report the techniques of functional near infrared spectroscopy for non-invasive evaluation in human study. The development of functional near infrared spectroscopy (fNIRS) technologies has advanced quantification signal using multiple wavelength and detector to solve the propagation of light inside the tissues including the absorption, scattering coefficient and to define the light penetration into tissues multilayers. There are a lot of studies that demonstrate signal from fNIRS which can be used to evaluate the changes of oxygenation level and measure the limitation of muscle performance in human brain and muscle tissues. Comprehensive reviews of diffuse reflectance based on beer lambert law theory were presented in this paper. The principle and development of fNIRS instrumentation is reported in detail.

  20. Defining cure.

    PubMed

    Hilton, Paul; Robinson, Dudley

    2011-06-01

    This paper is a summary of the presentations made as Proposal 2-"Defining cure" to the 2nd Annual meeting of the ICI-Research Society, in Bristol, 16th June 2010. It reviews definitions of 'cure' and 'outcome', and considers the impact that varying definition may have on prevalence studies and cure rates. The difference between subjective and objective outcomes is considered, and the significance that these different outcomes may have for different stakeholders (e.g. clinicians, patients, carers, industry etc.) is discussed. The development of patient reported outcome measures and patient defined goals is reviewed, and consideration given to the use of composite end-points. A series of proposals are made by authors and discussants as to how currently validated outcomes should be applied, and where our future research activity in this area might be directed.

  1. Toad heart utilizes exclusively slow skeletal muscle troponin T: an evolutionary adaptation with potential functional benefits.

    PubMed

    Feng, Han-Zhong; Chen, Xuequn; Hossain, M Moazzem; Jin, Jian-Ping

    2012-08-24

    The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2)-terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure.

  2. Toad heart utilizes exclusively slow skeletal muscle troponin T: an evolutionary adaptation with potential functional benefits.

    PubMed

    Feng, Han-Zhong; Chen, Xuequn; Hossain, M Moazzem; Jin, Jian-Ping

    2012-08-24

    The three isoforms of vertebrate troponin T (TnT) are normally expressed in a muscle type-specific manner. Here we report an exception that the cardiac muscle of toad (Bufo) expresses exclusively slow skeletal muscle TnT (ssTnT) together with cardiac forms of troponin I and myosin as determined using immunoblotting, cDNA cloning, and/or LC-MS/MS. Using RT-PCR and 3'- and 5'-rapid amplification of cDNA ends on toad cardiac mRNA, we cloned full-length cDNAs encoding two alternatively spliced variants of ssTnT. Expression of the cloned cDNAs in Escherichia coli confirmed that the toad cardiac muscle expresses solely ssTnT, predominantly the low molecular weight variant with the exon 5-encoded NH(2)-terminal segment spliced out. Functional studies were performed in ex vivo working toad hearts and compared with the frog (Rana) hearts. The results showed that toad hearts had higher contractile and relaxation velocities and were able to work against a significantly higher afterload than that of frog hearts. Therefore, the unique evolutionary adaptation of utilizing exclusively ssTnT in toad cardiac muscle corresponded to a fitness value from improving systolic function of the heart. The data demonstrated a physiological importance of the functional diversity of TnT isoforms. The structure-function relationship of TnT may be explored for the development of new treatment of heart failure. PMID:22778265

  3. Utility of wireless motility capsule and lactulose breath testing in the evaluation of patients with chronic functional bloating

    PubMed Central

    Triadafilopoulos, George

    2016-01-01

    Background The precise aetiology of chronic bloating remains poorly understood and underlying gastroparesis, small bowel bacterial overgrowth and colonic inertia may, individually or collectively, play a role. Aims In this retrospective cohort analysis of symptomatic patients with chronic persistent bloating, we determined the clinical utility of wireless motility capsule and lactulose breath test in further defining the underlying aetiology for functional bloating. Methods Consecutive patients with chronic bloating underwent clinical assessment, wireless motility capsule testing and lactulose breath testing using standard protocols. Results 52 patients qualified for inclusion in this analysis, fulfilling Rome III criteria for functional bloating. Most patients (54%) had an abnormal wireless motility capsule study; of those, 11.5% had evidence of gastroparesis, 7.7% had small bowel transit delay, 15.8% had colonic inertia, 3.8% had delayed gastric and small bowel transit, 5.6% had combined gastric and colonic transit delay, 3.8% had delayed small bowel and colonic transit, and 5.6% had delayed gastric, small bowel and colon transit times. Using clinical questionnaires the median scores for bloating, constipation and eructation were not significantly different. Neither constipation nor eructation was specific to gastroparesis or colonic inertia but bloating was numerically more prevalent and severe in patients with delayed small bowel transit. 40% of patients had positive lactulose breath test but had no distinguishing clinical characteristics. Conclusions Chronic functional bloating may reflect underlying gastroparesis, small intestinal bacterial overgrowth or colonic inertia. Wireless motility capsule and lactulose breath test are useful in the assessment of patients with bloating and should be considered during evaluation. PMID:27648298

  4. Utility of wireless motility capsule and lactulose breath testing in the evaluation of patients with chronic functional bloating

    PubMed Central

    Triadafilopoulos, George

    2016-01-01

    Background The precise aetiology of chronic bloating remains poorly understood and underlying gastroparesis, small bowel bacterial overgrowth and colonic inertia may, individually or collectively, play a role. Aims In this retrospective cohort analysis of symptomatic patients with chronic persistent bloating, we determined the clinical utility of wireless motility capsule and lactulose breath test in further defining the underlying aetiology for functional bloating. Methods Consecutive patients with chronic bloating underwent clinical assessment, wireless motility capsule testing and lactulose breath testing using standard protocols. Results 52 patients qualified for inclusion in this analysis, fulfilling Rome III criteria for functional bloating. Most patients (54%) had an abnormal wireless motility capsule study; of those, 11.5% had evidence of gastroparesis, 7.7% had small bowel transit delay, 15.8% had colonic inertia, 3.8% had delayed gastric and small bowel transit, 5.6% had combined gastric and colonic transit delay, 3.8% had delayed small bowel and colonic transit, and 5.6% had delayed gastric, small bowel and colon transit times. Using clinical questionnaires the median scores for bloating, constipation and eructation were not significantly different. Neither constipation nor eructation was specific to gastroparesis or colonic inertia but bloating was numerically more prevalent and severe in patients with delayed small bowel transit. 40% of patients had positive lactulose breath test but had no distinguishing clinical characteristics. Conclusions Chronic functional bloating may reflect underlying gastroparesis, small intestinal bacterial overgrowth or colonic inertia. Wireless motility capsule and lactulose breath test are useful in the assessment of patients with bloating and should be considered during evaluation.

  5. Towards spatially smart abatement of human pharmaceuticals in surface waters: Defining impact of sewage treatment plants on susceptible functions.

    PubMed

    Coppens, Lieke J C; van Gils, Jos A G; Ter Laak, Thomas L; Raterman, Bernard W; van Wezel, Annemarie P

    2015-09-15

    For human pharmaceuticals, sewage treatment plants (STPs) are a major point of entry to surface waters. The receiving waters provide vital functions. Modeling the impact of STPs on susceptible functions of the surface water system allows for a spatially smart implementation of abatement options at, or in the service area of, STPs. This study was performed on a nation-wide scale for the Netherlands. Point source emissions included were 345 Dutch STPs and nine rivers from neighboring countries. The Dutch surface waters were represented by 2511 surface water units. Modeling was performed for two extreme discharge conditions. Monitoring data of 7 locations along the rivers Rhine and Meuse fall mostly within the range of modeled concentrations. Half of the abstracted volumes of raw water for drinking water production, and a quarter of the Natura 2000 areas (European Union nature protection areas) hosted by the surface waters, are influenced by STPs at low discharge. The vast majority of the total impact of all Dutch STPs during both discharge conditions can be attributed to only 19% of the STPs with regard to the drinking water function, and to 39% of the STPs with regard to the Natura 2000 function. Attributing water treatment technologies to STPs as one of the possible measures to improve water quality and protect susceptible functions can be done in a spatially smart and cost-effective way, using consumption-based detailed hydrological and water quality modeling.

  6. Using expert knowledge and modeling to define mangrove composition, functioning, and threats and estimate time frame for recovery.

    PubMed

    Mukherjee, Nibedita; Sutherland, William J; Khan, Md Nabiul I; Berger, Uta; Schmitz, Nele; Dahdouh-Guebas, Farid; Koedam, Nico

    2014-06-01

    Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: "What is a mangrove ecosystem" and "How vulnerable are mangrove ecosystems to different impacts"? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors). PMID:25360265

  7. Using expert knowledge and modeling to define mangrove composition, functioning, and threats and estimate time frame for recovery.

    PubMed

    Mukherjee, Nibedita; Sutherland, William J; Khan, Md Nabiul I; Berger, Uta; Schmitz, Nele; Dahdouh-Guebas, Farid; Koedam, Nico

    2014-06-01

    Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: "What is a mangrove ecosystem" and "How vulnerable are mangrove ecosystems to different impacts"? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors).

  8. Using expert knowledge and modeling to define mangrove composition, functioning, and threats and estimate time frame for recovery

    PubMed Central

    Mukherjee, Nibedita; Sutherland, William J; Khan, Md Nabiul I; Berger, Uta; Schmitz, Nele; Dahdouh-Guebas, Farid; Koedam, Nico

    2014-01-01

    Mangroves are threatened worldwide, and their loss or degradation could impact functioning of the ecosystem. Our aim was to investigate three aspects of mangroves at a global scale: (1) their constituents (2) their indispensable ecological functions, and (3) the maintenance of their constituents and functions in degraded mangroves. We focused on answering two questions: “What is a mangrove ecosystem” and “How vulnerable are mangrove ecosystems to different impacts”? We invited 106 mangrove experts globally to participate in a survey based on the Delphi technique and provide inputs on the three aspects. The outputs from the Delphi technique for the third aspect, i.e. maintenance of constituents and functions were incorporated in a modeling approach to simulate the time frame for recovery. Presented here for the first time are the consensus definition of the mangrove ecosystem and the list of mangrove plant species. In this study, experts considered even monospecific (tree) stands to be a mangrove ecosystem as long as there was adequate tidal exchange, propagule dispersal, and faunal interactions. We provide a ranking of the important ecological functions, faunal groups, and impacts on mangroves. Degradation due to development was identified as having the largest impact on mangroves globally in terms of spatial scale, intensity, and time needed for restoration. The results indicate that mangroves are ecologically unique even though they may be species poor (from the vegetation perspective). The consensus list of mangrove species and the ranking of the mangrove ecological functions could be a useful tool for restoration and management of mangroves. While there is ample literature on the destruction of mangroves due to aquaculture in the past decade, this study clearly shows that more attention must go to avoiding and mitigating mangrove loss due to coastal development (such as building of roads, ports, or harbors). PMID:25360265

  9. Unemployment in multiple sclerosis (MS): utility of the MS Functional Composite and cognitive testing.

    PubMed

    Strober, Lauren; Chiaravalloti, Nancy; Moore, Nancy; DeLuca, John

    2014-01-01

    Unemployment is a significant concern among individuals with multiple sclerosis (MS). Determinations regarding ability to work are highly dependent on measurement tools used by neurologists and allied professionals. However, little is known of the usefulness of these tools when determining issues pertaining to employment status. The purpose of the present investigation was to examine the utility of the Multiple Sclerosis Functional Composite (MSFC) and a brief cognitive test battery when examining employment status in MS. Seventy-seven individuals with MS completed the MSFC and a brief cognitive test battery. On the MSFC, unemployed individuals demonstrated worse upper extremity functioning. There was no difference on the Paced Auditory Serial Addition Task (PASAT), the sole cognitive measure of the MSFC. On cognitive testing, unemployed individuals performed worse on measures of memory, information processing speed, and executive functioning. Through logistic regression analysis, the Symbol Digit Modalities Test (SDMT) was found to be the sole predictor of employment status among the significant disease, MSFC and cognitive variables. Consistent with previous findings, logistic regression found the SDMT to be a significant predictor of employment status. Given the lack of significant group differences on the PASAT, continued consideration of replacing the PASAT with the SDMT in the MSFC appears warranted.

  10. The Methionine Sulfoxide Reduction System: Selenium Utilization and Methionine Sulfoxide Reductase Enzymes and Their Functions

    PubMed Central

    2013-01-01

    Abstract Significance: Selenium is utilized in the methionine sulfoxide reduction system that occurs in most organisms. Methionine sulfoxide reductases (Msrs), MsrA and MsrB, are the enzymes responsible for this system. Msrs repair oxidatively damaged proteins, protect against oxidative stress, and regulate protein function, and have also been implicated in the aging process. Selenoprotein forms of Msrs containing selenocysteine (Sec) at the catalytic site are found in bacteria, algae, and animals. Recent Advances: A selenoprotein MsrB1 knockout mouse has been developed. Significant progress in the biochemistry of Msrs has been made, which includes findings of a novel reducing system for Msrs and of an interesting reason for the use of Sec in the Msr system. The effects of mammalian MsrBs, including selenoprotein MsrB1 on fruit fly aging, have been investigated. Furthermore, it is evident that Msrs are involved in methionine metabolism and regulation of the trans-sulfuration pathway. Critical Issues: This article presents recent progress in the Msr field while focusing on the physiological roles of mammalian Msrs, functions of selenoprotein forms of Msrs, and their biochemistry. Future Directions: A deeper understanding of the roles of Msrs in redox signaling, the aging process, and metabolism will be achieved. The identity of selenoproteome of Msrs will be sought along with characterization of the identified selenoprotein forms. Exploring new cellular targets and new functions of Msrs is also warranted. Antioxid. Redox Signal. 19, 958–969. PMID:23198996

  11. Defining Planktonic Protist Functional Groups on Mechanisms for Energy and Nutrient Acquisition: Incorporation of Diverse Mixotrophic Strategies.

    PubMed

    Mitra, Aditee; Flynn, Kevin J; Tillmann, Urban; Raven, John A; Caron, David; Stoecker, Diane K; Not, Fabrice; Hansen, Per J; Hallegraeff, Gustaaf; Sanders, Robert; Wilken, Susanne; McManus, George; Johnson, Mathew; Pitta, Paraskevi; Våge, Selina; Berge, Terje; Calbet, Albert; Thingstad, Frede; Jeong, Hae Jin; Burkholder, JoAnn; Glibert, Patricia M; Granéli, Edna; Lundgren, Veronica

    2016-04-01

    Arranging organisms into functional groups aids ecological research by grouping organisms (irrespective of phylogenetic origin) that interact with environmental factors in similar ways. Planktonic protists traditionally have been split between photoautotrophic "phytoplankton" and phagotrophic "microzooplankton". However, there is a growing recognition of the importance of mixotrophy in euphotic aquatic systems, where many protists often combine photoautotrophic and phagotrophic modes of nutrition. Such organisms do not align with the traditional dichotomy of phytoplankton and microzooplankton. To reflect this understanding, we propose a new functional grouping of planktonic protists in an eco-physiological context: (i) phagoheterotrophs lacking phototrophic capacity, (ii) photoautotrophs lacking phagotrophic capacity, (iii) constitutive mixotrophs (CMs) as phagotrophs with an inherent capacity for phototrophy, and (iv) non-constitutive mixotrophs (NCMs) that acquire their phototrophic capacity by ingesting specific (SNCM) or general non-specific (GNCM) prey. For the first time, we incorporate these functional groups within a foodweb structure and show, using model outputs, that there is scope for significant changes in trophic dynamics depending on the protist functional type description. Accordingly, to better reflect the role of mixotrophy, we recommend that as important tools for explanatory and predictive research, aquatic food-web and biogeochemical models need to redefine the protist groups within their frameworks. PMID:26927496

  12. Defining Planktonic Protist Functional Groups on Mechanisms for Energy and Nutrient Acquisition: Incorporation of Diverse Mixotrophic Strategies.

    PubMed

    Mitra, Aditee; Flynn, Kevin J; Tillmann, Urban; Raven, John A; Caron, David; Stoecker, Diane K; Not, Fabrice; Hansen, Per J; Hallegraeff, Gustaaf; Sanders, Robert; Wilken, Susanne; McManus, George; Johnson, Mathew; Pitta, Paraskevi; Våge, Selina; Berge, Terje; Calbet, Albert; Thingstad, Frede; Jeong, Hae Jin; Burkholder, JoAnn; Glibert, Patricia M; Granéli, Edna; Lundgren, Veronica

    2016-04-01

    Arranging organisms into functional groups aids ecological research by grouping organisms (irrespective of phylogenetic origin) that interact with environmental factors in similar ways. Planktonic protists traditionally have been split between photoautotrophic "phytoplankton" and phagotrophic "microzooplankton". However, there is a growing recognition of the importance of mixotrophy in euphotic aquatic systems, where many protists often combine photoautotrophic and phagotrophic modes of nutrition. Such organisms do not align with the traditional dichotomy of phytoplankton and microzooplankton. To reflect this understanding, we propose a new functional grouping of planktonic protists in an eco-physiological context: (i) phagoheterotrophs lacking phototrophic capacity, (ii) photoautotrophs lacking phagotrophic capacity, (iii) constitutive mixotrophs (CMs) as phagotrophs with an inherent capacity for phototrophy, and (iv) non-constitutive mixotrophs (NCMs) that acquire their phototrophic capacity by ingesting specific (SNCM) or general non-specific (GNCM) prey. For the first time, we incorporate these functional groups within a foodweb structure and show, using model outputs, that there is scope for significant changes in trophic dynamics depending on the protist functional type description. Accordingly, to better reflect the role of mixotrophy, we recommend that as important tools for explanatory and predictive research, aquatic food-web and biogeochemical models need to redefine the protist groups within their frameworks.

  13. INTERP3: A computer routine for linear interpolation of trivariate functions defined by nondistinct unequally spaced variables

    NASA Technical Reports Server (NTRS)

    Hill, D. C.; Morris, S. J., Jr.

    1979-01-01

    A report on the computer routine INTERP3 is presented. The routine is designed to linearly interpolate a variable which is a function of three independent variables. The variables within the parameter arrays do not have to be distinct, or equally spaced, and the array variables can be in increasing or decreasing order.

  14. Defining chaos

    SciTech Connect

    Hunt, Brian R.; Ott, Edward

    2015-09-15

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call “expansion entropy,” and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  15. Results of the ACSUS for pediatric AIDS patients: utilization of services, functional status, and social severity.

    PubMed Central

    Fahs, M C; Waite, D; Sesholtz, M; Muller, C; Hintz, E A; Maffeo, C; Arno, P; Bennett, C

    1994-01-01

    OBJECTIVE. This study describes demographic characteristics of pediatric AIDS patients, describes hospital and community-based service utilization patterns, and analyzes medical and social support service usage patterns with respect to patient demographic characteristics, clinical trial participation, functional/developmental status, and social environment. DATA SOURCES AND STUDY SETTING. Data reported in this study are from the AIDS Costs and Service Utilization Survey (ACSUS) and cover the six-month period beginning March 1991 (N = 135). Pediatric patients who sought care for HIV-related problems were sampled at seven different hospitals in five metropolitan regions of the United States. All of the participating hospitals had clinics specifically serving pediatric patients infected with HIV. The sample consists of HIV-positive patients who had had at least one HIV-related symptom or condition. STUDY DESIGN. A stratified probability sample design guided the sampling strategy, which included oversampling in two large hospitals from two of the five metropolitan areas. Survey data cover an 18-month time period of health care utilization, cost, and financing information from HIV-infected patients and their providers. Utilization measures are standardized to a six-month period. Per capita income, family structure, informal personal network, functional status, and clinical trial participation are tested for associations with patterns of utilization. In addition, a weighted ten-point social severity scale was developed to assess family/household stability. DATA COLLECTION. Data were collected through a screener instrument completed by the person accompanying the child to a hospital clinic visit (usually a a parent), and through two interviews conducted in person with the patients' primary caregivers. Data from the questionnaires were coded and assembled into computerized SAS analysis files by WESTAT. PRINCIPAL FINDINGS. Children in this sample are 62 percent African

  16. Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases.

    PubMed

    Floss, Doreen M; Klöcker, Tobias; Schröder, Jutta; Lamertz, Larissa; Mrotzek, Simone; Strobl, Birgit; Hermanns, Heike; Scheller, Jürgen

    2016-07-15

    The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor β1 (IL-12Rβ1) as one component of their receptor signaling complexes, with IL-12Rβ2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rβ1, whereas Jak2 binds to IL-23R and also to IL-12Rβ2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rβ1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rβ1 and Jak2 by IL‑23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable.

  17. Well-defined, size-tunable, multi-functional micelles for efficient paclitaxel delivery for cancer treatment

    PubMed Central

    Luo, Juntao; Xiao, Kai; Li, Yuanpei; Lee, Joyce S.; Shi, Lifang; Tan, Yih-Horng; Xing, Li; Cheng, R. Holland; Liu, Gang-Yu; Lam, Kit S.

    2010-01-01

    We have developed a well-defined and biocompatible amphiphilic telodendrimer system (PEG-b-dendritic oligo-cholic acid) which can self-assemble into multifunctional micelles in aqueous solution for efficient delivery of hydrophobic drugs such as paclitaxel. In this telodendrimer system, cholic acid is essential for the formation of stable micelles with high drug loading capacity, owing to its facial amphiphilicity. A series of telodendrimers with variable length of PEG chain and number of cholic acid in the dendritic blocks were synthesized. The structure and molecular weight of each of these telodendrimers were characterized, and their critical micellization concentration (CMC), drug-loading properties, particle sizes and cytotoxicity were examined and evaluated for further optimization for anticancer drug delivery. The sizes of the micelles, with and without paclitaxel loading, could be tuned from 11.5 to 21 nm and from 15 to 141 nm, respectively. Optical imaging studies in xenograft models demonstrated preferential uptakes of the smaller paclitaxel-loaded micelles (17–60 nm) by the tumor, and the larger micelles (150 nm) by the liver and lung. The toxicity and anti-tumor efficacy profiles of these paclitaxel-loaded micelles in xenograft models were found to be superior to those of Taxol® and Abraxane®. PMID:20536174

  18. Defining arthritis and measuring functional status in elders: methodological issues in the study of disease and physical disability.

    PubMed

    Guccione, A A; Felson, D T; Anderson, J J

    1990-08-01

    This study explores the degree to which the association of knee osteoarthritis with physical disability changes with different definitions of osteoarthritis in 1,416 Framingham Study elders. When all categories of radiographic osteoarthritis were aggregated into a single "arthritis" variable and dependence upon human assistance in one or more functional activities combined into a single variable, elders with osteoarthritis had only moderately increased odds for dependence after controlling for age or sex (OR = 1.25). A definition of osteoarthritis based only upon symptoms produced larger odds for dependency (OR = 1.85). Elders with mild osteoarthritis and infrequent knee pain had no significantly elevated risk for dependence in any of the seven functional activities. Elders with infrequently symptomatic, moderate to marked radiographic osteoarthritis were at increased risk for dependence in stair climbing, walking a mile, housekeeping, and carrying bundles. Elder with radiographic osteoarthritis accompanied by frequent pain had an increased odds of dependence in stair climbing, walking a mile, and housekeeping. Using a generic definition of "arthritis" and aggregating functional activities may underestimate the impact of osteoarthritis on physical disability in the elderly and obscure the task-specific nature of that relationship. PMID:2368855

  19. The IMMUTANS variegation locus of Arabidopsis defines a mitochondrial alternative oxidase homolog that functions during early chloroplast biogenesis.

    PubMed Central

    Wu, D; Wright, D A; Wetzel, C; Voytas, D F; Rodermel, S

    1999-01-01

    Nuclear gene-induced variegation mutants provide a powerful system to dissect interactions between the genetic systems of the nucleus-cytoplasm, the chloroplast, and the mitochondrion. The immutans (im) variegation mutation of Arabidopsis is nuclear and recessive and results in the production of green- and white-sectored leaves. The green sectors contain cells with normal chloroplasts, whereas the white sectors are heteroplastidic and contain cells with abnormal, pigment-deficient plastids as well as some normal chloroplasts. White sector formation can be promoted by enhanced light intensities, but sectoring becomes irreversible early in leaf development. The white sectors accumulate the carotenoid precursor phytoene. We have positionally cloned IM and found that the gene encodes a 40.5-kD protein with sequence motifs characteristic of alternative oxidase, a mitochondrial protein that functions as a terminal oxidase in the respiratory chains of all plants. However, phylogenetic analyses revealed that the IM protein is only distantly related to these other alternative oxidases, suggesting that IM is a novel member of this protein class. We sequenced three alleles of im, and all are predicted to be null. Our data suggest a model of variegation in which the IM protein functions early in chloroplast biogenesis as a component of a redox chain responsible for phytoene desaturation but that a redundant electron transfer function is capable of compensating for IM activity in some plastids and cells. PMID:9878631

  20. Defining arthritis and measuring functional status in elders: methodological issues in the study of disease and physical disability.

    PubMed Central

    Guccione, A A; Felson, D T; Anderson, J J

    1990-01-01

    This study explores the degree to which the association of knee osteoarthritis with physical disability changes with different definitions of osteoarthritis in 1,416 Framingham Study elders. When all categories of radiographic osteoarthritis were aggregated into a single "arthritis" variable and dependence upon human assistance in one or more functional activities combined into a single variable, elders with osteoarthritis had only moderately increased odds for dependence after controlling for age or sex (OR = 1.25). A definition of osteoarthritis based only upon symptoms produced larger odds for dependency (OR = 1.85). Elders with mild osteoarthritis and infrequent knee pain had no significantly elevated risk for dependence in any of the seven functional activities. Elders with infrequently symptomatic, moderate to marked radiographic osteoarthritis were at increased risk for dependence in stair climbing, walking a mile, housekeeping, and carrying bundles. Elder with radiographic osteoarthritis accompanied by frequent pain had an increased odds of dependence in stair climbing, walking a mile, and housekeeping. Using a generic definition of "arthritis" and aggregating functional activities may underestimate the impact of osteoarthritis on physical disability in the elderly and obscure the task-specific nature of that relationship. PMID:2368855

  1. The UlaG protein family defines novel structural and functional motifs grafted on an ancient RNase fold

    PubMed Central

    2011-01-01

    Background Bacterial populations are highly successful at colonizing new habitats and adapting to changing environmental conditions, partly due to their capacity to evolve novel virulence and metabolic pathways in response to stress conditions and to shuffle them by horizontal gene transfer (HGT). A common theme in the evolution of new functions consists of gene duplication followed by functional divergence. UlaG, a unique manganese-dependent metallo-β-lactamase (MBL) enzyme involved in L-ascorbate metabolism by commensal and symbiotic enterobacteria, provides a model for the study of the emergence of new catalytic activities from the modification of an ancient fold. Furthermore, UlaG is the founding member of the so-called UlaG-like (UlaGL) protein family, a recently established and poorly characterized family comprising divalent (and perhaps trivalent) metal-binding MBLs that catalyze transformations on phosphorylated sugars and nucleotides. Results Here we combined protein structure-guided and sequence-only molecular phylogenetic analyses to dissect the molecular evolution of UlaG and to study its phylogenomic distribution, its relatedness with present-day UlaGL protein sequences and functional conservation. Phylogenetic analyses indicate that UlaGL sequences are present in Bacteria and Archaea, with bona fide orthologs found mainly in mammalian and plant-associated Gram-negative and Gram-positive bacteria. The incongruence between the UlaGL tree and known species trees indicates exchange by HGT and suggests that the UlaGL-encoding genes provided a growth advantage under changing conditions. Our search for more distantly related protein sequences aided by structural homology has uncovered that UlaGL sequences have a common evolutionary origin with present-day RNA processing and metabolizing MBL enzymes widespread in Bacteria, Archaea, and Eukarya. This observation suggests an ancient origin for the UlaGL family within the broader trunk of the MBL superfamily by

  2. Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases

    PubMed Central

    Floss, Doreen M.; Klöcker, Tobias; Schröder, Jutta; Lamertz, Larissa; Mrotzek, Simone; Strobl, Birgit; Hermanns, Heike; Scheller, Jürgen

    2016-01-01

    The interleukin (IL)-12–type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor β1 (IL-12Rβ1) as one component of their receptor signaling complexes, with IL-12Rβ2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rβ1, whereas Jak2 binds to IL-23R and also to IL-12Rβ2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rβ1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12– and IL-23–induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rβ1 and Jak2 by IL‑23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable. PMID:27193299

  3. The antioxidative function, preventive action on disease and utilization of proanthocyanidins.

    PubMed

    Ariga, Toshiaki

    2004-01-01

    Proanthocyanidins, which belong to a class of polyphenols, are widely distributed throughout the plant kingdom. Most people ingest trace amounts of proanthocyanidins through foods such as red wine and cranberry juice. However, the functional properties of proanthocyanidins have been little understood. Since 1983, we have studied the antioxidative functions, preventive actions on diseases and utilization of proanthocyanidins. The antioxidative activities of proanthocyanidins were found to be much stronger than vitamin C or vitamin E in aqueous systems. The mechanisms for their antioxidative actions were shown to involve radical scavenging, quenching, and enzyme-inhibiting actions. The preventive actions of proanthcyanidins on diseases relating to reactive oxygen species was examined using animal tests. Proanthocyanidin-rich grape seed extract was showed to have preventive actions on diseases such as atherosclerosis, gastric ulcer, large bowel cancer, cataracts and diabetes. In human intervention trials, grape seed extract was shown to have preventive effects on the increase in lipid peroxides in human plasma after exercise and on muscle fatigue after training. The uses and manufacturing techniques of proanthocyanidin products were subsequently developed. The products were launched as antioxidants in food additives, ingredients in nutritional supplements, and cosmetics.

  4. Numerical information processing under the global rule expressed by the Euler-Riemann ζ function defined in the complex plane

    NASA Astrophysics Data System (ADS)

    Chatelin, Françoise

    2010-09-01

    When nonzero, the ζ function is intimately connected with numerical information processing. Two other functions play a key role, namely, η(s )=∑n ≥1(-1)n +1/ns and λ(s )=∑n ≥01/(2n+1)s. The paper opens on a survey of some of the seminal work of Euler [Mémoires Acad. Sci., Berlin 1768, 83 (1749)] and of the amazing theorem by Voronin [Math. USSR, Izv. 9, 443 (1975)] Then, as a follow-up of Chatelin [Qualitative Computing. A Computational Journey into Nonlinearity (World Scientific, Singapore, in press)], we present a fresh look at the triple (η ,ζ,λ) which suggests an elementary analysis based on the distances of the three complex numbers z, z /2, and 2/z to 0 and 1. This metric approach is used to contextualize any nonlinear computation when it is observed at a point describing a complex plane. The results applied to ζ, η, and λ shed a new epistemological light about the critical line. The suggested interpretation related to ζ carries computational significance.

  5. Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway

    PubMed Central

    Martin, Elizabeth; Ray, Paul D.; Smeester, Lisa; Grace, Matthew R.; Boggess, Kim; Fry, Rebecca C.

    2015-01-01

    Preeclampsia is a potentially fatal pregnancy disorder affecting millions of women around the globe. Dysregulation in gene and protein expression within key biological pathways controlling angiogenesis has been implicated in the development of preeclampsia. Altered CpG methylation, a type of epimutation, may underlie this pathway dysregulation. In the present study, placental tissue from preeclamptic cases and normotensive controls was analyzed for genome-wide differential CpG methylation and concomitant changes in gene expression. A set of 123 genes, representing 19.9% of all genes with altered CpG methylation, was associated with functional changes in transcript levels. Underscoring the complex relationships between CpG methylation and gene expression, here hypermethylation was never associated with gene silencing, nor was hypomethylation always associated with gene activation. Moreover, the genomic region of the CpG mark was important in predicting the relationship between CpG methylation and gene expression. The 123 genes were enriched for their involvement in the transforming growth factor beta (TGF-β) signaling pathway, a known regulator of placental trophoblast invasion and migration. This is the first study to identify CpG hypomethylation as an activator of TGF-β-associated gene expression in the preeclamptic placenta. The results suggest functional epimutations are associated with preeclampsia disease status and the identified genes may represent novel biomarkers of disease. PMID:26510177

  6. FURTHER DEFINING SPECTRAL TYPE 'Y' AND EXPLORING THE LOW-MASS END OF THE FIELD BROWN DWARF MASS FUNCTION

    SciTech Connect

    Davy Kirkpatrick, J.; Gelino, Christopher R.; Griffith, Roger L.; Marsh, Kenneth A.; Cushing, Michael C.; Mace, Gregory N.; Wright, Edward L.; McLean, Ian S.; Skrutskie, Michael F.; Eisenhardt, Peter R.; Mainzer, Amanda K.; Burgasser, Adam J.; Tinney, C. G.; Parker, Stephen; Salter, Graeme

    2012-07-10

    We present the discovery of another seven Y dwarfs from the Wide-field Infrared Survey Explorer (WISE). Using these objects, as well as the first six WISE Y dwarf discoveries from Cushing et al., we further explore the transition between spectral types T and Y. We find that the T/Y boundary roughly coincides with the spot where the J - H colors of brown dwarfs, as predicted by models, turn back to the red. Moreover, we use preliminary trigonometric parallax measurements to show that the T/Y boundary may also correspond to the point at which the absolute H (1.6 {mu}m) and W2 (4.6 {mu}m) magnitudes plummet. We use these discoveries and their preliminary distances to place them in the larger context of the solar neighborhood. We present a table that updates the entire stellar and substellar constituency within 8 pc of the Sun, and we show that the current census has hydrogen-burning stars outnumbering brown dwarfs by roughly a factor of six. This factor will decrease with time as more brown dwarfs are identified within this volume, but unless there is a vast reservoir of cold brown dwarfs invisible to WISE, the final space density of brown dwarfs is still expected to fall well below that of stars. We also use these new Y dwarf discoveries, along with newly discovered T dwarfs from WISE, to investigate the field substellar mass function. We find that the overall space density of late-T and early-Y dwarfs matches that from simulations describing the mass function as a power law with slope -0.5 < {alpha} < 0.0; however, a power law may provide a poor fit to the observed object counts as a function of spectral type because there are tantalizing hints that the number of brown dwarfs continues to rise from late-T to early-Y. More detailed monitoring and characterization of these Y dwarfs, along with dedicated searches aimed at identifying more examples, are certainly required.

  7. Defining the contributions of permanent electrostatics, Pauli repulsion, and dispersion in density functional theory calculations of intermolecular interaction energies.

    PubMed

    Horn, Paul R; Mao, Yuezhi; Head-Gordon, Martin

    2016-03-21

    In energy decomposition analysis of Kohn-Sham density functional theory calculations, the so-called frozen (or pre-polarization) interaction energy contains contributions from permanent electrostatics, dispersion, and Pauli repulsion. The standard classical approach to separate them suffers from several well-known limitations. We introduce an alternative scheme that employs valid antisymmetric electronic wavefunctions throughout and is based on the identification of individual fragment contributions to the initial supersystem wavefunction as determined by an energetic optimality criterion. The density deformations identified with individual fragments upon formation of the initial supersystem wavefunction are analyzed along with the distance dependence of the new and classical terms for test cases that include the neon dimer, ammonia borane, water-Na(+), water-Cl(-), and the naphthalene dimer. PMID:27004862

  8. Defining the contributions of permanent electrostatics, Pauli repulsion, and dispersion in density functional theory calculations of intermolecular interaction energies

    NASA Astrophysics Data System (ADS)

    Horn, Paul R.; Mao, Yuezhi; Head-Gordon, Martin

    2016-03-01

    In energy decomposition analysis of Kohn-Sham density functional theory calculations, the so-called frozen (or pre-polarization) interaction energy contains contributions from permanent electrostatics, dispersion, and Pauli repulsion. The standard classical approach to separate them suffers from several well-known limitations. We introduce an alternative scheme that employs valid antisymmetric electronic wavefunctions throughout and is based on the identification of individual fragment contributions to the initial supersystem wavefunction as determined by an energetic optimality criterion. The density deformations identified with individual fragments upon formation of the initial supersystem wavefunction are analyzed along with the distance dependence of the new and classical terms for test cases that include the neon dimer, ammonia borane, water-Na+, water-Cl-, and the naphthalene dimer.

  9. Defining the far-red limit of photosystem I: the primary charge separation is functional to 840 nm.

    PubMed

    Mokvist, Fredrik; Mamedov, Fikret; Styring, Stenbjörn

    2014-08-29

    The far-red limit of photosystem I (PS I) photochemistry was studied by EPR spectroscopy using laser flashes between 730 and 850 nm. In manganese-depleted spinach thylakoid membranes, the primary donor in PS I, P700, was oxidized simultaneously with tyrosine Z, the secondary donor in PS II. It was found that at 295 K PS I photochemistry, observed as P700 (+) formation, was functional up to 840 nm. This is 30 nm further to the red region than was reported for PS II photochemistry (Thapper, A., Mamedov, F., Mokvist, F., Hammarström, L., and Styring, S. (2009) Plant Cell 21, 2391-2401). The same far-red limit for the P700 (+) formation was observed in a PS I reaction center core preparation from Nostoc punctiforme. The reduction of the acceptor side of PS I, observed as reduction of the iron-sulfur centers FA and FB by low temperature EPR measurements, was also functional at 15 K with light up to >830 nm. Taken together, these results, obtained from both plants and cyanobacteria, most likely rule out involvement of the red-absorbing antenna chlorophylls in this reaction. Instead we propose the existence of weak charge transfer bands absorbing in the far-red region in the ensemble of excitonically coupled chlorophyll a molecules around P700 similar to what has been found in the reaction center of PS II. These charge transfer bands could be responsible for the far-red light absorption leading to PS I photochemistry at wavelengths up to 840 nm.

  10. Evaluation of a black-footed ferret resource utilization function model

    USGS Publications Warehouse

    Eads, D.A.; Millspaugh, J.J.; Biggins, D.E.; Jachowski, D.S.; Livieri, T.M.

    2011-01-01

    Resource utilization function (RUF) models permit evaluation of potential habitat for endangered species; ideally such models should be evaluated before use in management decision-making. We evaluated the predictive capabilities of a previously developed black-footed ferret (Mustela nigripes) RUF. Using the population-level RUF, generated from ferret observations at an adjacent yet distinct colony, we predicted the distribution of ferrets within a black-tailed prairie dog (Cynomys ludovicianus) colony in the Conata Basin, South Dakota, USA. We evaluated model performance, using data collected during post-breeding spotlight surveys (2007-2008) by assessing model agreement via weighted compositional analysis and count-metrics. Compositional analysis of home range use and colony-level availability, and core area use and home range availability, demonstrated ferret selection of the predicted Very high and High occurrence categories in 2007 and 2008. Simple count-metrics corroborated these findings and suggested selection of the Very high category in 2007 and the Very high and High categories in 2008. Collectively, these results suggested that the RUF was useful in predicting occurrence and intensity of space use of ferrets at our study site, the 2 objectives of the RUF. Application of this validated RUF would increase the resolution of habitat evaluations, permitting prediction of the distribution of ferrets within distinct colonies. Additional model evaluation at other sites, on other black-tailed prairie dog colonies of varying resource configuration and size, would increase understanding of influences upon model performance and the general utility of the RUF. ?? 2011 The Wildlife Society.

  11. Assessment of Global Functioning in Adolescents with Autism Spectrum Disorders: Utility of the Developmental Disability-Child Global Assessment Scale

    ERIC Educational Resources Information Center

    White, Susan W.; Smith, Laura A.; Schry, Amie R.

    2014-01-01

    Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment…

  12. Impact of lung function on exacerbations, health care utilization, and costs among patients with COPD

    PubMed Central

    Ke, Xuehua; Marvel, Jessica; Yu, Tzy-Chyi; Wertz, Debra; Geremakis, Caroline; Wang, Liya; Stephenson, Judith J; Mannino, David M

    2016-01-01

    Objective To evaluate the impact of lung function, measured as forced expiratory volume in 1 second (FEV1) % predicted, on health care resource utilization and costs among patients with COPD in a real-world US managed-care population. Methods This observational retrospective cohort study utilized administrative claim data augmented with medical record data. The study population consisted of patients with one or more medical claims for pre- and postbronchodilator spirometry during the intake period (July 1, 2012 to June 30, 2013). The index date was the date of the earliest medical claim for pre- and postbronchodilator spirometry. Spirometry results were abstracted from patients’ medical records. Patients were divided into two groups (low FEV1% predicted [,50%] and high FEV1% predicted [≥50%]) based on the 2014 Global Initiative for Chronic Obstructive Lung Disease report. Health care resource utilization and costs were based on the prevalence and number of discrete encounters during the 12-month postindex follow-up period. Costs were adjusted to 2014 US dollars. Results A total of 754 patients were included (n=297 low FEV1% predicted group, n=457 high FEV1% predicted group). COPD exacerbations were more prevalent in the low FEV1% predicted group compared with the high group during the 12-month pre- (52.5% vs 39.6%) and postindex periods (49.8% vs 36.8%). Mean (standard deviation) follow-up all-cause and COPD-related costs were $27,380 ($38,199) and $15,873 ($29,609) for patients in the low FEV1% predicted group, and $22,075 ($28,108) and $10,174 ($18,521) for patients in the high group. In the multivariable analyses, patients in the low FEV1% predicted group were more likely to have COPD exacerbations and tended to have higher COPD-related costs when compared with patients in the high group. Conclusion Real-world data demonstrate that patients with COPD who have low FEV1% predicted levels use more COPD medications, have more COPD exacerbations, and incur higher

  13. "Galaxy," Defined

    NASA Astrophysics Data System (ADS)

    Willman, B.; Strader, J.

    2012-09-01

    A growing number of low luminosity and low surface brightness astronomical objects challenge traditional notions of both galaxies and star clusters. To address this challenge, we propose a definition of galaxy that does not depend on a cold dark matter model of the universe: a galaxy is a gravitationally bound collection of stars whose properties cannot be explained by a combination of baryons and Newton's laws of gravity. After exploring several possible observational diagnostics of this definition, we critically examine the classification of ultra-faint dwarfs, globular clusters, ultra-compact dwarfs, and tidal dwarfs. While kinematic studies provide an effective diagnostic of the definition in many regimes, they can be less useful for compact or very faint systems. To explore the utility of using the [Fe/H] spread as a complementary diagnostic, we use published spectroscopic [Fe/H] measurements of 16 Milky Way dwarfs and 24 globular clusters to uniformly calculate their [Fe/H] spreads and associated uncertainties. Our principal results are (1) no known, old star cluster less luminous than MV = -10 has a significant (gsim0.1 dex) spread in its iron abundance; (2) known ultra-faint dwarf galaxies can be unambiguously classified with a combination of kinematic and [Fe/H] observations; (3) the observed [Fe/H] spreads in massive (gsim 106 M ⊙) globular clusters do not necessarily imply that they are the stripped nuclei of dwarfs, nor a need for dark matter; and (4) if ultra-compact dwarf galaxies reside in dark matter halos akin to those of ultra-faint dwarfs of the same half-light radii, then they will show no clear dynamical signature of dark matter. We suggest several measurements that may assist the future classification of massive globular clusters, ultra-compact dwarfs, and ultra-faint galaxies. Our galaxy definition is designed to be independent of the details of current observations and models, while our proposed diagnostics can be refined or replaced as

  14. On Defining Literacy.

    ERIC Educational Resources Information Center

    Sherritt, Caroline A.

    Defining literacy is a compelling challenge to educators. They generally use three models: instrumental, functional, and empowerment. The latter two approaches, which were increasingly evident in the 1980s, identify literacy by the social functions required in a given context or by the qualities needed for illiterate people to take control of…

  15. Surface attachment of well-defined redox-active polymers and block polymers via terminal functional groups

    SciTech Connect

    Albagli, D.; Bazan, G.C.; Schrock, R.R.; Wrighton, M.S. )

    1993-08-11

    Redox-active polymers and block polymers containing terminal groups for covalent attachment to surfaces have been prepared and characterized. Ferrocene- and phenothiazine-based redox-active polymers were prepared by ring-opening metathesis polymerization (ROMP) using Mo initiators of the type Mo(CHR)(NAr)(O-t-Bu)[sub 2] (R = tert-butyl or ferrocenyl, Ar = 2,6-diisopropylphenyl). The functional end groups introduced for surface attachment chemistry were Si(OEt)[sub 3], pyridyl, bromobenzyl, and pyrenyl derivatives. Polymers containing Si(OEt)[sub 3] were successfully used to derivatize Pt, In[sub 2](Sn)O[sub 3], and n-Si electrodes, whereas analogues of those same polymers lacking Si(OEt)[sub 3] groups do not bind to these surfaces. Polymers terminated with pyridyl or bromobenzyl groups, introduced in the capping reaction using the appropriate aldehydes, react with electrodes pretreated with benzyl chloride or pyridine groups, respectively, to give polymer-derivatized surfaces. Pyrene-capped polymers were made in an attempt to bind the polymers to carbon electrodes via selective pyrene adsorption. However, the polymer itself strongly adsorbs, precluding a specific role for the pyrene group. 37 refs., 8 figs.

  16. Co-ordinated functions of Mms proteins define the surface structure of cubo-octahedral magnetite crystals in magnetotactic bacteria.

    PubMed

    Arakaki, Atsushi; Yamagishi, Ayana; Fukuyo, Ayumi; Tanaka, Masayoshi; Matsunaga, Tadashi

    2014-08-01

    Magnetotactic bacteria synthesize magnetosomes comprised of membrane-enveloped single crystalline magnetite (Fe3 O4 ). The size and morphology of the nano-sized magnetite crystals (< 100 nm) are highly regulated and bacterial species dependent. However, the control mechanisms of magnetite crystal morphology remain largely unknown. The group of proteins, called Mms (Mms5, Mms6, Mms7, and Mms13), was previously isolated from the surface of cubo-octahedral magnetite crystals in Magnetospirillum magneticum strain AMB-1. Analysis of an mms6 gene deletion mutant suggested that the Mms6 protein plays a major role in the regulation of magnetite crystal size and morphology. In this study, we constructed various mms gene deletion mutants and characterized the magnetite crystals formed by the mutant strains. Comparative analysis showed that all mms genes were involved in the promotion of crystal growth in different manners. The phenotypic characterization of magnetites also suggested that these proteins are involved in controlling the geometries of the crystal surface structures. Thus, the co-ordinated functions of Mms proteins regulate the morphology of the cubo-octahedral magnetite crystals in magnetotactic bacteria.

  17. How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function.

    PubMed

    Schoenbaum, Geoffrey; Esber, Guillem R

    2010-04-01

    The past 15 years have seen a rapid increase in our understanding of orbitofrontal function. Today this region is the focus of an enormous amount of research, including work on such complex phenomena as regret, ambiguity, and willingness to pay. The orbitofrontal cortex is also credited as a major player in a host of neuropsychiatric diseases. This transformation arguably began with the application of concepts derived from animal learning theory. We will review data from studies emphasizing these approaches to argue that the orbitofrontal cortex forms a crucial part of a network of structures that signals information about expected outcomes. Further we will suggest that, within this network, the orbitofrontal cortex provides the critical ability to integrate information in real-time to make what amounts to actionable predictions or estimates about future outcomes. As we will show, the influence of these estimates can be demonstrated experimentally in appropriate behavioral settings, and their operation can also readily explain the role of orbitofrontal cortex in much more complex phenomena such as those cited above.

  18. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+ CD25+ T cells.

    PubMed

    Baecher-Allan, Clare; Wolf, Elizabeth; Hafler, David A

    2005-04-01

    The importance of CD4+ CD25+ regulatory T cells (Treg) in maintaining immune homeostasis has been directly demonstrated in vivo by their manipulation in a number of autoimmune disease models in the mouse. In the study of human regulatory cells, we have found that the cells that consistently demonstrate the in vitro regulatory activity most similar to that described for murine cells in vitro are best identified by restricting the isolation of CD25+ CD4 T cells to those cells expressing only the highest levels of CD25, representing approximately 2-3% of total CD4 T cells. Thus, it is the CD4+ CD25high subset that exhibits the in vitro characteristics that are identical to the CD4+ CD25+ regulatory cells initially characterized in mice. Furthermore, the cells expressing medium to low levels of CD25 not only do not exhibit suppressive activity directly ex vivo, but also actually contain a significant proportion of CD62L- CD4 T cells which are believed to be in vivo activated T cells. Due to the inherent difficulties in using CD25 as a marker for the purification of Treg cells, the finding that selection of the CD25high subset of CD4+ CD25+ T cells minimizes the co-isolation of contaminating activated CD4 T cells is important for future studies of these Treg cells in human disease. In order to perform these studies, we first had to establish a highly reproducible 'micro in vitro co-culture' assay system to enable the functional analysis of high-purity, but low-yield regulatory populations derived from FACS sorting. With this system in place, we are poised to dissect the potential heterogeneity of mechanisms employed by highly specific subpopulations of CD4+ CD25+ cells.

  19. Isolation and proteomic characterization of the Arabidopsis Golgi defines functional and novel components involved in plant cell wall biosynthesis.

    PubMed

    Parsons, Harriet T; Christiansen, Katy; Knierim, Bernhard; Carroll, Andrew; Ito, Jun; Batth, Tanveer S; Smith-Moritz, Andreia M; Morrison, Stephanie; McInerney, Peter; Hadi, Masood Z; Auer, Manfred; Mukhopadhyay, Aindrila; Petzold, Christopher J; Scheller, Henrik V; Loqué, Dominique; Heazlewood, Joshua L

    2012-05-01

    The plant Golgi plays a pivotal role in the biosynthesis of cell wall matrix polysaccharides, protein glycosylation, and vesicle trafficking. Golgi-localized proteins have become prospective targets for reengineering cell wall biosynthetic pathways for the efficient production of biofuels from plant cell walls. However, proteomic characterization of the Golgi has so far been limited, owing to the technical challenges inherent in Golgi purification. In this study, a combination of density centrifugation and surface charge separation techniques have allowed the reproducible isolation of Golgi membranes from Arabidopsis (Arabidopsis thaliana) at sufficiently high purity levels for in-depth proteomic analysis. Quantitative proteomic analysis, immunoblotting, enzyme activity assays, and electron microscopy all confirm high purity levels. A composition analysis indicated that approximately 19% of proteins were likely derived from contaminating compartments and ribosomes. The localization of 13 newly assigned proteins to the Golgi using transient fluorescent markers further validated the proteome. A collection of 371 proteins consistently identified in all replicates has been proposed to represent the Golgi proteome, marking an appreciable advancement in numbers of Golgi-localized proteins. A significant proportion of proteins likely involved in matrix polysaccharide biosynthesis were identified. The potential within this proteome for advances in understanding Golgi processes has been demonstrated by the identification and functional characterization of the first plant Golgi-resident nucleoside diphosphatase, using a yeast complementation assay. Overall, these data show key proteins involved in primary cell wall synthesis and include a mixture of well-characterized and unknown proteins whose biological roles and importance as targets for future research can now be realized. PMID:22430844

  20. The functional importance of a cap site-proximal region of the human prointerleukin 1[beta] gene is defined

    SciTech Connect

    Hunninghake, G.W.; Geist, L.J.; Monick, M.M.; Stinski, M.F. ); Monks, B.G.; Monroy, M.A.; Fenton, M.J. ); Webb, A.C. ); Dayer, J.M. ); Auron, P.E. )

    1992-08-01

    Prointerleukin 1[beta] (IL-1[beta]) is a cytokine that mediates a broad range of biological activities. Genomic sequences that regulate IL-1[beta] transcription include both inducible regulatory elements located more than 2,700 bp upstream of the transcriptional start site (cap site) and proximal elements located near the TATA box of this gene. In this study, we focused on the identification and characterization of trans-acting nuclear regulatory proteins that bind to the cap site-proximal region of the human IL-1[beta] gene. We identified a protein, termed NFIL-1[beta]A (NF[beta]A), that binds to a highly conserved 12-bp DNA sequence (-49 to -38) located upstream of the TATA box motif in both the human and murine IL-1[beta] genes. The IL-1[alpha] gene, which lacks a TATA motif, does not possess an NF[beta]A-binding sequence within the promoter region, suggesting that NF[beta]A may selectively regulate IL-1[beta] expression. Using electrophoretic mobility shift assays, we identified several distinct DNA-protein complexes that are expressed in a cell-type-specific manner. In monocytic cell lines, the relative abundance of these complexes varied rapidly following stimulation of the cells with phorbol esters or lipopolysaccharide. UV cross-linking analysis identified two distinct DNA-binding polypeptides that comprise distinct complexes. The functional role of NF[beta]A was assessed in transient transfection assays. These data indicate the NF[beta]A is required for both basal and inducible promoter activity in monocytic cells. Furthermore, the human cytomegalovirus immediate-early 1 gene product requires the presence of NF[beta]A in order to trans-activate the proximal IL-1[beta] promoter in a monocytic cell line. We propose that NF[beta]A is a factor that mediates either direct or indirect activation by the immediate-early 1 gene product. The proximity of this essential factor to the TATA motif suggests a possible role in transcriptional initiation.

  1. High Performance Nonvolatile Transistor Memories Utilizing Functional Polyimide-Based Supramolecular Electrets.

    PubMed

    Tung, Wei-Yao; Li, Meng-Hsien; Wu, Hung-Chin; Liu, Hsin-Yu; Hsieh, Yun-Ting; Chen, Wen-Chang

    2016-05-20

    We report pentacene-based organic field-effect transistor memory devices utilizing supramolecular electrets, consisting of a polyimide, PI(6FOH-ODPA), containing hydroxyl groups for hydrogen bonding with amine functionalized aromatic rings (AM) of 1-aniline (AM1), 2-naphthylamine (AM2), 2-aminoanthracene (AM3), and 1-aminopyrene (AM4). The effect of the phenyl ring size and composition of AM1-AM4 on the hole-trapping capability of the fabricated devices was investigated systematically. Under an operating voltage under ±40 V, the prepared devices using the electrets of 100 % AM1-AM4/PI ratios exhibited a memory window of 0, 8.59, 25.97, and 29.95 V, respectively, suggesting that the hole-trapping capability increased with enhancing phenyl ring size. The memory window was enhanced as the amount of AM in PI increased. Furthermore, the devices showed a long charge-retention time of 10(4)  s with an ON/OFF current ratio of around 10(3) -10(4) and multiple switching stability over 100 cycles. This study demonstrated that the electrical characteristics of the OFET memory devices could be manipulated through the chemical compositions of the supramolecular electrets.

  2. Use of Multi-attribute Utility Functions in Evaluating Security Systems

    SciTech Connect

    Meyers, C; Lamont, A; Sicherman, A

    2008-06-13

    In analyzing security systems, we are concerned with protecting a building or facility from an attack by an adversary. Typically, we address the possibility that an adversary could enter a building and cause damage resulting in an immediate loss of life, or at least substantial disruption in the operations of the facility. In response to this setting, we implement security systems including devices, procedures, and facility upgrades designed to (a) prevent the adversary from entering, (b) detect and neutralize him if he does enter, and (c) harden the facility to minimize damage if an attack is carried out successfully. Although we have cast this in terms of physical protection of a building, the same general approach can be applied to non-physical attacks such as cyber attacks on a computer system. A rigorous analytic process is valuable for quantitatively evaluating an existing system, identifying its weaknesses, and proposing useful upgrades. As such, in this paper we describe an approach to assess the degree of overall protection provided by security measures. Our approach evaluates the effectiveness of the individual components of the system, describes how the components work together, and finally assesses the degree of overall protection achieved. This model can then be used to quantify the amount of protection provided by existing security measures, as well as to address proposed upgrades to the system and help identify a robust and cost effective set of improvements. Within the model, we use multiattribute utility functions to perform the overall evaluations of the system.

  3. Complex-scaling of screened Coulomb potentials for resonance calculations utilizing the modified Bessel functions

    NASA Astrophysics Data System (ADS)

    Jiao, Li-Guang; Ho, Yew Kam

    2014-05-01

    The screened Coulomb potential (SCP) has been extensively used in atomic physics, nuclear physics, quantum chemistry and plasma physics. However, an accurate calculation for atomic resonances under SCP is still a challenging task for various methods. Within the complex-scaling computational scheme, we have developed a method utilizing the modified Bessel functions to calculate doubly-excited resonances in two-electron atomic systems with configuration interaction-type basis. To test the validity of our method, we have calculated S- and P-wave resonance states of the helium atom with various screening strengths, and have found good agreement with earlier calculations using different methods. Our present method can be applied to calculate high-lying resonances associated with high excitation thresholds of the He+ ion, and with high-angular-momentum states. The derivation and calculation details of our present investigation together with new results of high-angular-momentum states will be presented at the meeting. Supported by NSC of Taiwan.

  4. Investigating the Function of an Arabinan Utilization Locus Isolated from a Termite Gut Community

    PubMed Central

    Arnal, Grégory; Bastien, Géraldine; Monties, Nelly; Abot, Anne; Anton Leberre, Véronique; Bozonnet, Sophie; O'Donohue, Michael

    2014-01-01

    Biocatalysts are essential for the development of bioprocesses efficient for plant biomass degradation. Previously, a metagenomic clone containing DNA from termite gut microbiota was pinpointed in a functional screening that revealed the presence of arabinofuranosidase activity. Subsequent genetic and bioinformatic analysis revealed that the DNA fragment belonged to a member of the genus Bacteroides and encoded 19 open reading frames (ORFs), and annotation suggested the presence of hypothetical transporter and regulator proteins and others involved in the catabolism of pentose sugar. In this respect and considering the phenotype of the metagenomic clone, it was noted that among the ORFs, there are four putative arabinose-specific glycoside hydrolases, two from family GH43 and two from GH51. In this study, a thorough bioinformatics analysis of the metagenomic clone gene cluster has been performed and the four aforementioned glycoside hydrolases have been characterized. Together, the results provide evidence that the gene cluster is a polysaccharide utilization locus dedicated to the breakdown of the arabinan component in pectin and related substrates. Characterization of the two GH43 and the two GH51 glycoside hydrolases has revealed that each of these enzymes displays specific catalytic capabilities and that when these are combined the enzymes act synergistically, increasing the efficiency of arabinan degradation. PMID:25304507

  5. Utility of preoperative in vitro platelet function tests for predicting bleeding risk in patients undergoing functional endoscopic sinus surgery

    PubMed Central

    Lee, A-Jin; Kim, Sang-Gyung

    2016-01-01

    Background It is necessary to predict the bleeding risk in patients undergoing functional endoscopic sinus surgery (FESS). To evaluate the adequacy of primary hemostasis, preoperative hemostatic screening tests are used. In the present study, we determined whether there is a positive correlation between prolonged closure time (CT) with collagen/epinephrine (CT-epi), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) and bleeding during FESS. Patients and methods We reviewed the medical records of 90 patients without bleeding histories who had undergone FESS from March 2013 to June 2014. More than 200 mL of blood loss was defined as moderate bleeding during surgery. With respect to bleeding during surgery, we determined the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of CT-epi, PT, INR and aPTT. Results Of the 90 patients, 17 (18.9%) patients had preoperative prolonged CT values and three (17.6%) patients had bleeding. In comparison, five (6.8%) of the 73 (81.1%) patients who had undergone FESS with preoperative normal PFA values experienced bleeding (P=0.171). On the other hand, patients with prolonged PT values (2, 2.2%), prolonged INR values (3, 3.3%) or prolonged PTT values (1, 1.1%) had no bleeding episode. Preoperative CT had low sensitivity (44.4%) and PPV (23.5%). Conclusion During preoperative period, the hemostatic screening may not be helpful to detect the bleeding tendency in adult patients undergoing FESS. Routine measurement of CT-epi, PT, INR and aPTT for preoperative screening may not be recommended for FESS patients. PMID:27799837

  6. Structure-Function Analysis of 2-Keto-3-Deoxy-D-Glycero-D-Galacto-Nononate-9-Phosphate Phosphatase Defines Specificity Elements in Type C0 had Family Members

    SciTech Connect

    Lu, Z.; Wang, L; Dunaway-Mariano, D; Allen, K

    2009-01-01

    The phosphotransferases of the haloalkanoate dehalogenase superfamily (HADSF) act upon a wide range of metabolites in all eukaryotes and prokaryotes and thus constitute a significant force in cell function. The challenge posed for biochemical function assignment of HADSF members is the identification of the structural determinants that target a specific metabolite. The '8KDOP' subfamily of the HADSF is defined by the known structure and catalytic activity of 2-keto-3-deoxy-8-phospho-d-manno-octulosonic acid (KDO-8-P) phosphatase. Homologues of this enzyme have been uniformly annotated as KDO-8-P phosphatase. One such gene, BT1713, from the Bacteroides thetaiotaomicron genome was recently found to encode the enzyme 2-keto-3-deoxy-d-glycero-d-galacto-9-phosphonononic acid (KDN-9-P) phosphatase in the biosynthetic pathway of the 9-carbon ?-keto acid, 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN). To find the structural elements that provide substrate-specific interactions and to allow identification of genomic sequence markers, the x-ray crystal structures of BT1713 liganded to the cofactor Mg2+and complexed with tungstate or Formula/Neu5Ac were determined to 1.1, 1.85, and 1.63 A resolution, respectively. The structures define the active site to be at the subunit interface and, as confirmed by steady-state kinetics and site-directed mutagenesis, reveal Arg-64*, Lys-67*, and Glu-56 to be the key residues involved in sugar binding that are essential for BT1713 catalytic function. Bioinformatic analyses of the differentially conserved residues between BT1713 and KDO-8-P phosphatase homologues guided by the knowledge of the structure-based specificity determinants define Glu-56 and Lys-67* to be the key residues that can be used in future annotations.

  7. Parameterization of rainfall-runoff models by using utility functions for the reproduction of low and average flows

    NASA Astrophysics Data System (ADS)

    Baratti, Emanuele; Montanari, Alberto; Toth, Elena

    2014-05-01

    In the majority of rainfall-runoff modelling applications, the objective function to be minimised in the parameterisation procedure is the mean square error or another quadratic function (such as the Nash-Sutcliff efficiency). Since the use of squares forces an arbitrarily greater influence of large errors, generally corresponding to large streamflow values, such choice may prevent the identification of an adequate input-output relationship for the reproduction of low and average flows. This contribution presents the results of a series of calibration/validation experiments with a conceptual rainfall-runoff model, applied over several case-study catchments, where the performance function is based on the expected utility of the rainfall-runoff model. The method is based on the evidence that the performances of a hydrological model closely depend on the purpose of the application. For instance, in a flood forecasting system, the model could be used to estimate peak flow conditions (e.g. peak time and peak flow rate), whereas in a water resources management system, it could be particularly appreciated the capability of the model to reproduce the discharges for the entire year, or, in particular, those of water scarcity periods. In the proposed method, at each time step, the comparison between simulated and observed data is carried out by using an 'ad-hoc' utility function. The calibration is performed by maximizing the overall estimated utility of the simulated data. Different utility functions are tested and the results are compared, over validation data, against those obtained with traditional squared functions. The results reveal that an adequate utility function allows an improvement of the model performances in the reproduction of low and average flows, with a moderate deterioration of the simulation of high flows. It is also pointed out as the traditional calibration procedures may be considered as a particular case of the presented approach.

  8. Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model.

    PubMed

    Plaza Reyes, Alvaro; Petrus-Reurer, Sandra; Antonsson, Liselotte; Stenfelt, Sonya; Bartuma, Hammurabi; Panula, Sarita; Mader, Theresa; Douagi, Iyadh; André, Helder; Hovatta, Outi; Lanner, Fredrik; Kvanta, Anders

    2016-01-12

    Human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells could replace lost tissue in geographic atrophy (GA) but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model. PMID:26724907

  9. Hierarchical decomposition of burn body diagram based on cutaneous functional units and its utility.

    PubMed

    Richard, Reg; Jones, John A; Parshley, Philip

    2015-01-01

    A burn body diagram (BBD) is a common feature used in the delivery of burn care for estimating the TBSA burn as well as calculating fluid resuscitation and nutritional requirements, wound healing, and rehabilitation intervention. However, little change has occurred for over seven decades in the configuration of the BBD. The purpose of this project was to develop a computerized model using hierarchical decomposition (HD) to more precisely determine the percentage burn within a BBD based on cutaneous functional units (CFUs). HD is a process by which a system is degraded into smaller parts that are more precise in their use. CFUs were previously identified fields of the skin involved in the range of motion. A standard Lund/Browder (LB) BBD template was used as the starting point to apply the CFU segments. LB body divisions were parceled down into smaller body area divisions through a HD process based on the CFU concept. A numerical pattern schema was used to label the various segments in a cephalo/caudal, anterior/posterior, medial/lateral manner. Hand/fingers were divided based on anatomical landmarks and known cutaneokinematic function. The face was considered using aesthetic units. Computer code was written to apply the numeric hierarchical schema to CFUs and applied within the context of the surface area graphic evaluation BBD program. Each segmented CFU was coded to express 100% of itself. The CFU/HD method refined the standard LB diagram from 13 body segments and 33 subdivisions into 182 isolated CFUs. Associated CFUs were reconstituted into 219 various surface area combinations totaling 401 possible surface segments. The CFU/HD schema of the body surface mapping is applicable to measuring and calculating percent wound healing in a more precise manner. It eliminates subjective assessment of the percentage wound healing and the need for additional devices such as planimetry. The development of CFU/HD body mapping schema has rendered a technologically advanced

  10. Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

    PubMed Central

    Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip’ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

    2016-01-01

    Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease. PMID:27251104

  11. Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions

    NASA Astrophysics Data System (ADS)

    Kutikhin, Anton G.; Velikanova, Elena A.; Mukhamadiyarov, Rinat A.; Glushkova, Tatiana V.; Borisov, Vadim V.; Matveeva, Vera G.; Antonova, Larisa V.; Filip’Ev, Dmitriy E.; Golovkin, Alexey S.; Shishkova, Daria K.; Burago, Andrey Yu.; Frolov, Alexey V.; Dolgov, Viktor Yu.; Efimova, Olga S.; Popova, Anna N.; Malysheva, Valentina Yu.; Vladimirov, Alexandr A.; Sozinov, Sergey A.; Ismagilov, Zinfer R.; Russakov, Dmitriy M.; Lomzov, Alexander A.; Pyshnyi, Dmitriy V.; Gutakovsky, Anton K.; Zhivodkov, Yuriy A.; Demidov, Evgeniy A.; Peltek, Sergey E.; Dolganyuk, Viatcheslav F.; Babich, Olga O.; Grigoriev, Evgeniy V.; Brusina, Elena B.; Barbarash, Olga L.; Yuzhalin, Arseniy E.

    2016-06-01

    Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

  12. Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions.

    PubMed

    Kutikhin, Anton G; Velikanova, Elena A; Mukhamadiyarov, Rinat A; Glushkova, Tatiana V; Borisov, Vadim V; Matveeva, Vera G; Antonova, Larisa V; Filip'ev, Dmitriy E; Golovkin, Alexey S; Shishkova, Daria K; Burago, Andrey Yu; Frolov, Alexey V; Dolgov, Viktor Yu; Efimova, Olga S; Popova, Anna N; Malysheva, Valentina Yu; Vladimirov, Alexandr A; Sozinov, Sergey A; Ismagilov, Zinfer R; Russakov, Dmitriy M; Lomzov, Alexander A; Pyshnyi, Dmitriy V; Gutakovsky, Anton K; Zhivodkov, Yuriy A; Demidov, Evgeniy A; Peltek, Sergey E; Dolganyuk, Viatcheslav F; Babich, Olga O; Grigoriev, Evgeniy V; Brusina, Elena B; Barbarash, Olga L; Yuzhalin, Arseniy E

    2016-01-01

    Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease. PMID:27251104

  13. The thick aleurone1 mutant defines a negative regulation of maize aleurone cell fate that functions downstream of defective kernel1.

    PubMed

    Yi, Gibum; Lauter, Adrienne M; Scott, M Paul; Becraft, Philip W

    2011-08-01

    The maize (Zea mays) aleurone layer occupies the single outermost layer of the endosperm. The defective kernel1 (dek1) gene is a central regulator required for aleurone cell fate specification. dek1 mutants have pleiotropic phenotypes including lack of aleurone cells, aborted embryos, carotenoid deficiency, and a soft, floury endosperm deficient in zeins. Here we describe the thick aleurone1 (thk1) mutant that defines a novel negative function in the regulation of aleurone differentiation. Mutants possess multiple layers of aleurone cells as well as aborted embryos. Clonal sectors of thk1 mutant tissue in otherwise normal endosperm showed localized expression of the phenotype with sharp boundaries, indicating a localized cellular function for the gene. Sectors in leaves showed expanded epidermal cell morphology but the mutant epidermis generally remained in a single cell layer. Double mutant analysis indicated that the thk1 mutant is epistatic to dek1 for several aspects of the pleiotropic dek1 phenotype. dek1 mutant endosperm that was mosaic for thk1 mutant sectors showed localized patches of multilayered aleurone. Localized sectors were surrounded by halos of carotenoid pigments and double mutant kernels had restored zein profiles. In sum, loss of thk1 function restored the ability of dek1 mutant endosperm to accumulate carotenoids and zeins and to differentiate aleurone. Therefore the thk1 mutation defines a negative regulator that functions downstream of dek1 in the signaling system that controls aleurone specification and other aspects of endosperm development. The thk1 mutation was found to be caused by a deletion of approximately 2 megabases.

  14. The Utility of the MMPI-2 Malingering Discriminant Function Index in the Detection of Malingering: A Study of Criminal Defendants

    ERIC Educational Resources Information Center

    Toomey, Joseph A.; Kucharski, L. Thomas; Duncan, Scott

    2009-01-01

    This study examined the utility of the Minnesota Multiphasic Personality Inventory-2's (MMPI-2) malingering discriminant function index (M-DFI), recently developed by Bacchiochi and Bagby, in the detection of malingering in a forensic sample. Criminal defendants were divided into "malingering" and "not malingering" groups using the structured…

  15. Utility of the International Classification of Functioning, Disability and Health (ICF) for Educational Psychologists' Work

    ERIC Educational Resources Information Center

    Aljunied, Mariam; Frederickson, Norah

    2014-01-01

    Despite embracing a bio-psycho-social perspective, the World Health Organization's International Classification of Functioning, Disability and Health (ICF) assessment framework has had limited application to date with children who have special educational needs (SEN). This study examines its utility for educational psychologists' work…

  16. An Electroactive, Tunable, and Frequency Selective Surface Utilizing Highly Stretchable Dielectric Elastomer Actuators Based on Functionally Antagonistic Aperture Control.

    PubMed

    Choi, Jun-Ho; Ahn, Jaeho; Kim, Jin-Bong; Kim, Young-Cheol; Lee, Jung-Yong; Oh, Il-Kwon

    2016-04-13

    An active, frequency selective surface utilizing a silver-nanowire-coated dielectric elastomer with a butterfly-shaped aperture pattern is realized by properly exploiting the electroactive control of two antagonistic functions (stretching vs compression) on a patterned dielectric elastomer actuator. PMID:26864249

  17. Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

    2006-01-01

    /16 crewmembers exhibited significant strategic motor learning patterns in their micro curves, as defined by m > 1 in the equation of the line y=m*LN(x) +b. These data indicate that postflight recovery in locomotor function involves both strategic and adaptive mechanisms. Future countermeasures will be designed to enhance both recovery processes.

  18. Labview utilities

    2011-09-30

    The software package provides several utilities written in LabView. These utilities don't form independent programs, but rather can be used as a library or controls in other labview programs. The utilities include several new controls (xcontrols), VIs for input and output routines, as well as other 'helper'-functions not provided in the standard LabView environment.

  19. The importance of chemistry in creating well-defined nanoscopic embedded therapeutics: devices capable of the dual functions of imaging and therapy.

    PubMed

    Nyström, Andreas M; Wooley, Karen L

    2011-10-18

    Nanomedicine is a rapidly evolving field, for which polymer building blocks are proving useful for the construction of sophisticated devices that provide enhanced diagnostic imaging and treatment of disease, known as theranostics. These well-defined nanoscopic objects have high loading capacities, can protect embedded therapeutic cargo, and offer control over the conditions and rates of release. Theranostics also offer external surface area for the conjugation of ligands to impart stealth characteristics and/or direct their interactions with biological receptors and provide a framework for conjugation of imaging agents to track delivery to diseased site(s). The nanoscopic dimensions allow for extensive biological circulation. The incorporation of such multiple functions is complicated, requiring exquisite chemical control during production and rigorous characterization studies to confirm the compositions, structures, properties, and performance. We are particularly interested in the study of nanoscopic objects designed for treatment of lung infections and acute lung injury, urinary tract infections, and cancer. This Account highlights our work over several years to tune the assembly of unique nanostructures. We provide examples of how the composition, structure, dimensions, and morphology of theranostic devices can tune their performance as drug delivery agents for the treatment of infectious diseases and cancer. The evolution of nanostructured materials from relatively simple overall shapes and internal morphologies to those of increasing complexity is driving the development of synthetic methodologies for the preparation of increasingly complex nanomedicine devices. Our nanomedicine devices are derived from macromolecules that have well-defined compositions, structures, and topologies, which provide a framework for their programmed assembly into nanostructures with controlled sizes, shapes, and morphologies. The inclusion of functional units within selective

  20. The importance of chemistry in creating well-defined nanoscopic embedded therapeutics: devices capable of the dual functions of imaging and therapy.

    PubMed

    Nyström, Andreas M; Wooley, Karen L

    2011-10-18

    Nanomedicine is a rapidly evolving field, for which polymer building blocks are proving useful for the construction of sophisticated devices that provide enhanced diagnostic imaging and treatment of disease, known as theranostics. These well-defined nanoscopic objects have high loading capacities, can protect embedded therapeutic cargo, and offer control over the conditions and rates of release. Theranostics also offer external surface area for the conjugation of ligands to impart stealth characteristics and/or direct their interactions with biological receptors and provide a framework for conjugation of imaging agents to track delivery to diseased site(s). The nanoscopic dimensions allow for extensive biological circulation. The incorporation of such multiple functions is complicated, requiring exquisite chemical control during production and rigorous characterization studies to confirm the compositions, structures, properties, and performance. We are particularly interested in the study of nanoscopic objects designed for treatment of lung infections and acute lung injury, urinary tract infections, and cancer. This Account highlights our work over several years to tune the assembly of unique nanostructures. We provide examples of how the composition, structure, dimensions, and morphology of theranostic devices can tune their performance as drug delivery agents for the treatment of infectious diseases and cancer. The evolution of nanostructured materials from relatively simple overall shapes and internal morphologies to those of increasing complexity is driving the development of synthetic methodologies for the preparation of increasingly complex nanomedicine devices. Our nanomedicine devices are derived from macromolecules that have well-defined compositions, structures, and topologies, which provide a framework for their programmed assembly into nanostructures with controlled sizes, shapes, and morphologies. The inclusion of functional units within selective

  1. Evaluation of the Utility of a Discrete-Trial Functional Analysis in Early Intervention Classrooms

    ERIC Educational Resources Information Center

    Kodak, Tiffany; Fisher, Wayne W.; Paden, Amber; Dickes, Nitasha

    2013-01-01

    We evaluated a discrete-trial functional analysis implemented by regular classroom staff in a classroom setting. The results suggest that the discrete-trial functional analysis identified a social function for each participant and may require fewer staff than standard functional analysis procedures.

  2. [An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

    PubMed

    Hideo, Sakaguchi

    2014-06-01

    Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

  3. The phylogenetic utility and functional constraint of microRNA flanking sequences

    PubMed Central

    Kenny, Nathan J.; Sin, Yung Wa; Hayward, Alexander; Paps, Jordi; Chu, Ka Hou; Hui, Jerome H. L.

    2015-01-01

    MicroRNAs (miRNAs) have recently risen to prominence as novel factors responsible for post-transcriptional regulation of gene expression. miRNA genes have been posited as highly conserved in the clades in which they exist. Consequently, miRNAs have been used as rare genome change characters to estimate phylogeny by tracking their gain and loss. However, their short length (21–23 bp) has limited their perceived utility in sequenced-based phylogenetic inference. Here, using reference taxa with established phylogenetic relationships, we demonstrate that miRNA sequences are of high utility in quantitative, rather than in qualitative, phylogenetic analysis. The clear orthology among miRNA genes from different species makes it straightforward to identify and align these sequences from even fragmentary datasets. We also identify significant sequence conservation in the regions directly flanking miRNA genes, and show that this too is of utility in phylogenetic analysis, as well as highlighting conserved regions that will be of interest to other fields. Employing miRNA sequences from 12 sequenced drosophilid genomes, together with a Tribolium castaneum outgroup, we demonstrate that this approach is robust using Bayesian and maximum-likelihood methods. The utility of these characters is further demonstrated in the rhabditid nematodes and primates. As next-generation sequencing makes it more cost-effective to sequence genomes and small RNA libraries, this methodology provides an alternative data source for phylogenetic analysis. The approach allows rapid resolution of relationships between both closely related and rapidly evolving species, and provides an additional tool for investigation of relationships within the tree of life. PMID:25694624

  4. Determining firms׳ utility functions and competitive roles from data on market shares using Lotka–Volterra models

    PubMed Central

    Marasco, A.; Picucci, A.; Romano, A.

    2016-01-01

    In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963–2000) and biannual data on the market shares of the mobile phones market in Greece (1998–2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms’ utility functions and their competitive roles. PMID:27054182

  5. Determining firms׳ utility functions and competitive roles from data on market shares using Lotka-Volterra models.

    PubMed

    Marasco, A; Picucci, A; Romano, A

    2016-06-01

    In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963-2000) and biannual data on the market shares of the mobile phones market in Greece (1998-2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms' utility functions and their competitive roles.

  6. Determining firms׳ utility functions and competitive roles from data on market shares using Lotka-Volterra models.

    PubMed

    Marasco, A; Picucci, A; Romano, A

    2016-06-01

    In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963-2000) and biannual data on the market shares of the mobile phones market in Greece (1998-2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms' utility functions and their competitive roles. PMID:27054182

  7. Supraspliceosomes at defined functional states portray the pre-assembled nature of the pre-mRNA processing machine in the cell nucleus.

    PubMed

    Kotzer-Nevo, Hani; de Lima Alves, Flavia; Rappsilber, Juri; Sperling, Joseph; Sperling, Ruth

    2014-06-30

    When isolated from mammalian cell nuclei, all nuclear pre-mRNAs are packaged in multi-subunit large ribonucleoprotein complexes-supraspliceosomes-composed of four native spliceosomes interconnected by the pre-mRNA. Supraspliceosomes contain all five spliceosomal U snRNPs, together with other splicing factors, and are functional in splicing. Supraspliceosomes studied thus far represent the steady-state population of nuclear pre-mRNAs that were isolated at different stages of the splicing reaction. To analyze specific splicing complexes, here, we affinity purified Pseudomonas aeruginosa phage 7 (PP7)-tagged splicing complexes assembled in vivo on Adenovirus Major Late (AdML) transcripts at specific functional stages, and characterized them using molecular techniques including mass spectrometry. First, we show that these affinity purified splicing complexes assembled on PP7-tagged AdML mRNA or on PP7-tagged AdML pre-mRNA are assembled in supraspliceosomes. Second, similar to the general population of supraspliceosomes, these defined supraspliceosomes populations are assembled with all five U snRNPs at all splicing stages. This study shows that dynamic changes in base-pairing interactions of U snRNA:U snRNA and U snRNA:pre-mRNA that occur in vivo during the splicing reaction do not require changes in U snRNP composition of the supraspliceosome. Furthermore, there is no need to reassemble a native spliceosome for the splicing of each intron, and rearrangements of the interactions will suffice.

  8. A new human natural killer leukemia cell line, IMC-1. A complex chromosomal rearrangement defined by spectral karyotyping: functional and cytogenetic characterization.

    PubMed

    Chen, I-Ming; Whalen, Margaret; Bankhurst, Arthur; Sever, Cordelia E; Doshi, Rashmi; Hardekopf, David; Montgomery, Karen; Willman, Cheryl L

    2004-03-01

    A new human IL-2 dependent leukemic cell line with a natural killer (NK) cell phenotype, IMC-1, was established from an adult patient with aggressive NK cell leukemia. The IMC-1 cell line expresses the CD56, CD2, CD11a, CD38 and HLA-DR cell surface antigens, whereas the CD16 and CD8 antigens expressed on the primary leukemic blasts from which the cell line was derived were lost after 7 and 28 weeks of culture, respectively. The IMC-1 cell line displays functional NK cytotoxicity and lyses target cells in a non-MHC restricted, antibody-independent manner with equal or superior efficiency to freshly isolated NK cells. Cytogenetic analysis at presentation and after 55 weeks in culture revealed complex structural and numerical abnormalities, defined by classic G-banding and by spectral karyotyping (SKY). Three apparently intact copies of chromosome 8 occurred in the diagnostic bone marrow specimen; the cell line also contains three copies of chromosome 8 but each was structurally altered. The development and detailed characterization of this new NK leukemic cell line will facilitate biologic and functional studies of NK cells and chromosomal aberrations potentially important in leukemic transformation.

  9. Method for utilizing properties of the sinc(x) function for phase retrieval on nyquist-under-sampled data

    NASA Technical Reports Server (NTRS)

    Dean, Bruce H. (Inventor); Smith, Jeffrey Scott (Inventor); Aronstein, David L. (Inventor)

    2012-01-01

    Disclosed herein are systems, methods, and non-transitory computer-readable storage media for simulating propagation of an electromagnetic field, performing phase retrieval, or sampling a band-limited function. A system practicing the method generates transformed data using a discrete Fourier transform which samples a band-limited function f(x) without interpolating or modifying received data associated with the function f(x), wherein an interval between repeated copies in a periodic extension of the function f(x) obtained from the discrete Fourier transform is associated with a sampling ratio Q, defined as a ratio of a sampling frequency to a band-limited frequency, and wherein Q is assigned a value between 1 and 2 such that substantially no aliasing occurs in the transformed data, and retrieves a phase in the received data based on the transformed data, wherein the phase is used as feedback to an optical system.

  10. Serum-free, chemically defined medium with TGF-beta(3) enhances functional properties of nucleus pulposus cell-laden carboxymethylcellulose hydrogel constructs.

    PubMed

    Reza, Anna T; Nicoll, Steven B

    2010-02-01

    Degeneration of the nucleus pulposus (NP) has been implicated as a major cause of low back pain. Tissue engineering strategies may provide a viable NP replacement therapy; however, culture conditions must be optimized to promote functional tissue development. In this study, a standard serum-containing medium formulation was compared to a chemically defined, serum-free medium to determine the effect on matrix elaboration and functional properties of NP cell-laden carboxymethylcellulose (CMC) hydrogels. Additionally, both media were further supplemented with transforming growth factor-beta 3 (TGF-beta(3)). Glycosaminoglycan (GAG) content increased in both TGF-beta(3)-treated groups and was highest for treated, serum-free constructs (9.46 +/- 1.51 microg GAG/mg wet weight), while there were no quantifiable GAGs in untreated serum-containing samples. Histology revealed uniform, interterritorial staining for chondroitin sulfate proteoglycan throughout the treated, serum-free constructs. Type II collagen content was greater in both serum-free groups and highest in treated, serum-free constructs. The equilibrium Young's modulus was highest in serum-free samples supplemented with TGF-beta(3) (18.54 +/- 1.92 kPa), and the equilibrium weight swelling ratio of these constructs approached that of the native NP tissue (22.19 +/- 0.46 vs. 19.94 +/- 3.09, respectively). Taken together, these results demonstrate enhanced functional matrix development by NP cells when cultured in CMC hydrogels maintained in serum-free, TGF-beta(3) supplemented medium, indicating the importance of medium formulation in NP construct development. PMID:19777586

  11. Failure to utilize functions of an electronic prescribing system and the subsequent generation of ‘technically preventable’ computerized alerts

    PubMed Central

    Reckmann, Margaret H; Li, Ling; Day, Richard O; Westbrook, Johanna I

    2012-01-01

    Objectives To determine the frequency with which computerized alerts occur and the proportion triggered as a result of prescribers not utilizing e-prescribing system functions. Methods An audit of electronic inpatient medication charts at a teaching hospital in Sydney, Australia, was conducted to identify alerts fired, to categorize the system functions used by prescribers, and to assess if use of short-cut system functions could have prevented the alerts. Results Of the 2209 active orders reviewed, 600 (27.2%) triggered at least one alert. Therapeutic duplication alerts were the most frequent (n=572). One third of these (20.2% of all alerts) was ‘technically preventable’ and would not have fired if prescribers had used a short-cut system function to prescribe. Under-utilized system functions included the option to ‘MODIFY’ existing orders and use of the ‘AND’ function for concurrent orders. Pregnancy alerts, set for women aged between 12 and 55 years, were triggered for 43% of drugs ordered for this group. Conclusion Developers of decision support systems should test the extent to which technically preventable alerts may arise when prescribers fail to use system functions as designed. Designs which aim to improve the efficiency of the prescribing process but which do not align with the cognitive processes of users may fail to achieve this desired outcome and produce unexpected consequences such as triggering unnecessary alerts and user frustration. Ongoing user training to support effective use of e-prescribing system functions and modifications to the mechanisms underlying alert generation are needed to ensure that prescribers are presented with fewer but more meaningful alerts. PMID:22735616

  12. The Utility of CDOM for Improving the Resolution of Riverine DOM Fluxes and Biogeochemical Function

    NASA Astrophysics Data System (ADS)

    Spencer, R. G.; Aiken, G.; Mann, P. J.; Holmes, R. M.; Niggemann, J.; Dittmar, T.; Hernes, P.; Stubbins, A.

    2014-12-01

    A major historical limitation to geochemical studies assessing fluvial fluxes of dissolved organic matter (DOM) has been the issue of both temporal and spatial scaling. Examples will be presented from watersheds around the world highlighting how chromophoric dissolved organic matter (CDOM) measurements can be utilized as proxies for more intensive and expensive analytical analyses (e.g. molecular-level organic biomarkers). Utilizing these refined CDOM loads for terrigenous biomarkers results in improved temporal resolution and a significant change in flux estimates. Examining CDOM and dissolved organic carbon (DOC) flux data from an assortment of terrestrial biomes we establish a robust relationship between CDOM and DOC loads. The application of this relationship allows future studies to derive DOC loads from CDOM utilizing emerging in-situ or remote sensing technologies and thus refine river-to-ocean DOC fluxes, as well as exploit historic imagery to examine how fluxes may have changed. Calculated CDOM yields from a range of rivers are correlated to watershed percent wetland and highlight the importance of certain regions with respect to CDOM flux to the coastal ocean. This approach indicates that future studies might predict CDOM and DOC yields for different watershed types that could then be readily converted to loads providing for the estimation of CDOM and DOC export from ungauged watersheds. Examination of CDOM yields also highlights important geographical regions for future study with respect to the role of terrigenous CDOM in ocean color budgets and CDOM's role in biogeochemical processes. Finally, examples will be presented linking CDOM parameters to DOM composition and biogeochemical properties with the aim of providing measurements to improve the spatial and especially temporal resolution of the role DOM plays in fluvial networks.

  13. Impairment in occupational functioning and adult ADHD: the predictive utility of executive function (EF) ratings versus EF tests.

    PubMed

    Barkley, Russell A; Murphy, Kevin R

    2010-05-01

    Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct.

  14. Functional Genomics Screening Utilizing Mutant Mouse Embryonic Stem Cells Identifies Novel Radiation-Response Genes

    PubMed Central

    Loesch, Kimberly; Galaviz, Stacy; Hamoui, Zaher; Clanton, Ryan; Akabani, Gamal; Deveau, Michael; DeJesus, Michael; Ioerger, Thomas; Sacchettini, James C.; Wallis, Deeann

    2015-01-01

    Elucidating the genetic determinants of radiation response is crucial to optimizing and individualizing radiotherapy for cancer patients. In order to identify genes that are involved in enhanced sensitivity or resistance to radiation, a library of stable mutant murine embryonic stem cells (ESCs), each with a defined mutation, was screened for cell viability and gene expression in response to radiation exposure. We focused on a cancer-relevant subset of over 500 mutant ESC lines. We identified 13 genes; 7 genes that have been previously implicated in radiation response and 6 other genes that have never been implicated in radiation response. After screening, proteomic analysis showed enrichment for genes involved in cellular component disassembly (e.g. Dstn and Pex14) and regulation of growth (e.g. Adnp2, Epc1, and Ing4). Overall, the best targets with the highest potential for sensitizing cancer cells to radiation were Dstn and Map2k6, and the best targets for enhancing resistance to radiation were Iqgap and Vcan. Hence, we provide compelling evidence that screening mutant ESCs is a powerful approach to identify genes that alter radiation response. Ultimately, this knowledge can be used to define genetic variants or therapeutic targets that will enhance clinical therapy. PMID:25853515

  15. Hybrid diversity method utilizing adaptive diversity function for recovering unknown aberrations in an optical system

    NASA Technical Reports Server (NTRS)

    Dean, Bruce H. (Inventor)

    2009-01-01

    A method of recovering unknown aberrations in an optical system includes collecting intensity data produced by the optical system, generating an initial estimate of a phase of the optical system, iteratively performing a phase retrieval on the intensity data to generate a phase estimate using an initial diversity function corresponding to the intensity data, generating a phase map from the phase retrieval phase estimate, decomposing the phase map to generate a decomposition vector, generating an updated diversity function by combining the initial diversity function with the decomposition vector, generating an updated estimate of the phase of the optical system by removing the initial diversity function from the phase map. The method may further include repeating the process beginning with iteratively performing a phase retrieval on the intensity data using the updated estimate of the phase of the optical system in place of the initial estimate of the phase of the optical system, and using the updated diversity function in place of the initial diversity function, until a predetermined convergence is achieved.

  16. Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions.

    PubMed

    de Souza, Robson Francisco; Aravind, L

    2012-06-01

    Nicotinamide adenine dinucleotide (NAD) is a ubiquitous cofactor participating in numerous redox reactions. It is also a substrate for regulatory modifications of proteins and nucleic acids via the addition of ADP-ribose moieties or removal of acyl groups by transfer to ADP-ribose. In this study, we use in-depth sequence, structure and genomic context analysis to uncover new enzymes and substrate-binding proteins in NAD-utilizing metabolic and macromolecular modification systems. We predict that Escherichia coli YbiA and related families of domains from diverse bacteria, eukaryotes, large DNA viruses and single strand RNA viruses are previously unrecognized components of NAD-utilizing pathways that probably operate on ADP-ribose derivatives. Using contextual analysis we show that some of these proteins potentially act in RNA repair, where NAD is used to remove 2'-3' cyclic phosphodiester linkages. Likewise, we predict that another family of YbiA-related enzymes is likely to comprise a novel NAD-dependent ADP-ribosylation system for proteins, in conjunction with a previously unrecognized ADP-ribosyltransferase. A similar ADP-ribosyltransferase is also coupled with MACRO or ADP-ribosylglycohydrolase domain proteins in other related systems, suggesting that all these novel systems are likely to comprise pairs of ADP-ribosylation and ribosylglycohydrolase enzymes analogous to the DraG-DraT system, and a novel group of bacterial polymorphic toxins. We present evidence that some of these coupled ADP-ribosyltransferases/ribosylglycohydrolases are likely to regulate certain restriction modification enzymes in bacteria. The ADP-ribosyltransferases found in these, the bacterial polymorphic toxin and host-directed toxin systems of bacteria such as Waddlia also throw light on the evolution of this fold and the origin of eukaryotic polyADP-ribosyltransferases and NEURL4-like ARTs, which might be involved in centrosomal assembly. We also infer a novel biosynthetic pathway that

  17. Utilization of microscale silicon cantilevers to assess cellular contractile function in vitro

    PubMed Central

    Smith, Alec S.T.; Long, Christopher J.; McAleer, Christopher; Bobbitt, Nathaniel; Srinivasan, Balaji; Hickman, James J.

    2016-01-01

    The development of more predictive and biologically relevant in vitro assays is predicated on the advancement of versatile cell culture systems which facilitate the functional assessment of the seeded cells. To that end, microscale cantilever technology offers a platform with which to measure the contractile functionality of a range of cell types, including skeletal, cardiac and smooth muscle cells, through assessment of contraction induced substrate bending. Application of multiplexed cantilever arrays provides the means to develop moderate to high-throughput protocols for assessing drug efficacy and toxicity, disease phenotype and progression, as well as neuromuscular and other cell-cell interactions. This manuscript provides the details for fabricating reliable cantilever arrays for this purpose, and the methods required to successfully culture cells on these surfaces. Further description is provided on the steps necessary to perform functional analysis of contractile cell types maintained on such arrays using a novel laser and photo-detector system. The representative data provided highlights the precision and reproducible nature of the analysis of contractile function possible using this system, as well as the wide range of studies to which such technology can be applied. Successful widespread adoption of this system could provide investigators with the means to perform rapid, low cost functional studies in vitro, leading to more accurate predictions of tissue performance, disease development and response to novel therapeutic treatment. PMID:25350792

  18. Utilization of Microscale Silicon Cantilevers to Assess Cellular Contractile Function In Vitro

    PubMed Central

    Smith, Alec S.T.; Long, Christopher J.; McAleer, Christopher; Bobbitt, Nathaniel; Srinivasan, Balaji; Hickman, James J.

    2014-01-01

    The development of more predictive and biologically relevant in vitro assays is predicated on the advancement of versatile cell culture systems which facilitate the functional assessment of the seeded cells. To that end, microscale cantilever technology offers a platform with which to measure the contractile functionality of a range of cell types, including skeletal, cardiac, and smooth muscle cells, through assessment of contraction induced substrate bending. Application of multiplexed cantilever arrays provides the means to develop moderate to high-throughput protocols for assessing drug efficacy and toxicity, disease phenotype and progression, as well as neuromuscular and other cell-cell interactions. This manuscript provides the details for fabricating reliable cantilever arrays for this purpose, and the methods required to successfully culture cells on these surfaces. Further description is provided on the steps necessary to perform functional analysis of contractile cell types maintained on such arrays using a novel laser and photo-detector system. The representative data provided highlights the precision and reproducible nature of the analysis of contractile function possible using this system, as well as the wide range of studies to which such technology can be applied. Successful widespread adoption of this system could provide investigators with the means to perform rapid, low cost functional studies in vitro, leading to more accurate predictions of tissue performance, disease development and response to novel therapeutic treatment. PMID:25350792

  19. Well-defined azlactone-functionalized (co)polymers on a solid support: synthesis via supported living radical polymerization and application as nucleophile scavengers.

    PubMed

    Fournier, David; Pascual, Sagrario; Montembault, Véronique; Haddleton, David M; Fontaine, Laurent

    2006-01-01

    Wang resin has been converted to a supported initiator for transition metal-mediated living radical polymerization often called atom-transfer radical polymerization (ATRP) of 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) and styrene (S). Several "Rasta" resins with well-defined macromolecular architectures, including homopolymers PVDM, PS, statistical P(S-stat-VDM), block P(S-b-VDM), and P[S-b-(S-stat-VDM)] copolymers, have been elaborated. For the homopolymerization of VDM and S, a sacrificial initiator, benzyl 2-bromoisobutyrate (BBI), has been introduced to monitor the evolution of molar masses and polydispersity indexes (PDIs) of PS and PVDM onto the Wang resin support without cleavage. After 6 h, 86.7% conversion of VDM is reached, with the isolated PVDM chains having a molar mass of 18 000 g mol(-1) and a PDI value of 1.22. Block copolymers have been synthesized in two steps, involving the synthesis of the PS block isolated at low conversions (<15%) to maintain the bromine end-chain functionality and the subsequent synthesis of the second PVDM or P(S-stat-VDM) block. Polydispersity indexes of the cleaved (co)polymers were low (PDI = 1.11-1.44), and high azlactone loadings have been reached (loading = 6.0 mmol g(-1)). Such azlactone-functionalized Wang resins have shown high efficiency during the scavenging process of benzylamine as monitored by HPLC. Moreover, grafted statistical copolymers have shown the best behavior for removing benzylamine because of an improvement of the accessibility of azlactone rings by the dilution with styrene units. PMID:16827564

  20. SU-E-T-614: Derivation of Equations to Define Inflection Points and Its Analysis in Flattening Filter Free Photon Beams Based On the Principle of Polynomial function

    SciTech Connect

    Muralidhar, K Raja; Komanduri, K

    2014-06-01

    Purpose: The objective of this work is to present a mechanism for calculating inflection points on profiles at various depths and field sizes and also a significant study on the percentage of doses at the inflection points for various field sizes and depths for 6XFFF and 10XFFF energy profiles. Methods: Graphical representation was done on Percentage of dose versus Inflection points. Also using the polynomial function, the authors formulated equations for calculating spot-on inflection point on the profiles for 6X FFF and 10X FFF energies for all field sizes and at various depths. Results: In a flattening filter free radiation beam which is not like in Flattened beams, the dose at inflection point of the profile decreases as field size increases for 10XFFF. Whereas in 6XFFF, the dose at the inflection point initially increases up to 10x10cm2 and then decreases. The polynomial function was fitted for both FFF beams for all field sizes and depths. For small fields less than 5x5 cm2 the inflection point and FWHM are almost same and hence analysis can be done just like in FF beams. A change in 10% of dose can change the field width by 1mm. Conclusion: The present study, Derivative of equations based on the polynomial equation to define inflection point concept is precise and accurate way to derive the inflection point dose on any FFF beam profile at any depth with less than 1% accuracy. Corrections can be done in future studies based on the multiple number of machine data. Also a brief study was done to evaluate the inflection point positions with respect to dose in FFF energies for various field sizes and depths for 6XFFF and 10XFFF energy profiles.

  1. An industrial perspective on utilizing functional ion channel assays for high throughput screening.

    PubMed

    Worley, Jennings F; Main, Martin J

    2002-01-01

    The ability to apply large-scale screening formats to measures of ion channel function offers immense opportunities for drug discovery and academic research. Technologies have been developed over the last several years that now provide the ability to screen large numbers of compounds and natural products on ion channel function to find novel drugs. Application of these technologies has vastly improved the capabilities of ion channel drug discovery and provides an avenue to accelerate discoveries of ion channel biology. These advances have largely arisen from the development and application of instruments and reporters of membrane potential and ion movements in cells used to measure functional activity of ion channels. This article endeavors to describe the practical applications of these technologies in developing, validating, and implementing high throughput screening assay formats to different types of ion channels.

  2. Development of a Functional Biohybrid Implant Formed from Periodontal Tissue Utilizing Bioengineering Technology.

    PubMed

    Nakajima, Kei; Oshima, Masamitsu; Yamamoto, Naomi; Tanaka, Chie; Koitabashi, Ryosuke; Inoue, Takashi; Tsuji, Takashi

    2016-09-01

    Current osseointegrated dental implants have been widely used for the rehabilitation of tooth loss. Although dental implants are considered an available treatment in the paradigm shift from traditional dental therapies, such as fixed dental bridges and removable dentures, the fundamental problems must be overcome before their clinical use in young patients who are still undergoing jawbone growth. Here, we show a novel bioengineering method for a functional biohybrid implant that is combined with adult-derived periodontal tissue and attached with bone tissue as a substitute for cementum. This biohybrid implant was successfully engrafted using the bioengineered periodontal ligament, and it restored physiological function, such as orthodontic movement through bone remodeling and appropriate responsiveness to noxious stimuli. Thus, this study represents the functional biohybrid implant's potential for clinical use as a next-generation dental implant using adult-derived tissues.

  3. Delineating potential epileptogenic areas utilizing resting functional magnetic resonance imaging (fMRI) in epilepsy patients.

    PubMed

    Pizarro, Ricardo; Nair, Veena; Meier, Timothy; Holdsworth, Ryan; Tunnell, Evelyn; Rutecki, Paul; Sillay, Karl; Meyerand, Mary E; Prabhakaran, Vivek

    2016-08-01

    Seizure localization includes neuroimaging like electroencephalogram, and magnetic resonance imaging (MRI) with limited ability to characterize the epileptogenic network. Temporal clustering analysis (TCA) characterizes epileptogenic network congruent with interictal epileptiform discharges by clustering together voxels with transient signals. We generated epileptogenic areas for 12 of 13 epilepsy patients with TCA, congruent with different areas of seizure onset. Resting functional MRI (fMRI) scans are noninvasive, and can be acquired quickly, in patients with different levels of severity and function. Analyzing resting fMRI data using TCA is quick and can complement clinical methods to characterize the epileptogenic network. PMID:27362339

  4. Boundary value problem of Pontryagin's maximum principle in a two-sector economy model with an integral utility function

    NASA Astrophysics Data System (ADS)

    Kiselev, Yu. N.; Orlov, M. V.; Orlov, S. M.

    2015-11-01

    An infinite-horizon two-sector economy model with a Cobb-Douglas production function and a utility function that is an integral functional with discounting and a logarithmic integrand is investigated. The application of Pontryagin's maximum principle yields a boundary value problem with special conditions at infinity. The search for the solution of the maximum-principle boundary value problem is complicated by singular modes in its optimal solution. In the construction of the solution to the problem, they are described in analytical form. Additionally, a special version of the sweep method in continuous form is proposed, which is of interest from theoretical and computational points of view. An important result is the proof of the optimality of the extremal solution obtained by applying the maximum-principle boundary value problem.

  5. The Utility of the Lambert Function W[a exp(a - bt)] in Chemical Kinetics

    ERIC Educational Resources Information Center

    Williams, Brian Wesley

    2010-01-01

    The mathematical Lambert function W[a exp(a - bt)] is used to find integrated rate laws for several examples, including simple enzyme and Lindemann-Christiansen-Hinshelwood (LCH) unimolecular decay kinetics. The results derived here for the well-known LCH mechanism as well as for a dimer-monomer reaction mechanism appear to be novel. A nonlinear…

  6. Evaluation of the Treatment Utility of the Analog Functional Analysis and the Structured Descriptive Assessment

    ERIC Educational Resources Information Center

    English, Carie L.; Anderson, Cynthia M.

    2006-01-01

    Direct methods of functional assessment--through which information is gathered by observing environment--behavior relations--vary with the degree to which environmental events are manipulated. Unstructured (ABC) assessments involve observing the occurrence of problem behavior without altering environmental events in any way. At the other extreme,…

  7. Athletes and Sedentary Individuals: An Intergroup Comparison Utilizing a Pulmonary Function Ratio Obtained During Submaximal Exercise.

    ERIC Educational Resources Information Center

    Maud, Peter J.

    A pulmonary function ratio describing oxygen extraction from alveolar ventilation was used for an intergroup comparison between three groups of athletes (rugby, basketball, and football players) and one group of sedentary subjects during steady-state submaximal exercise. The ratio and its component parts are determined from only three gas…

  8. A Study on the Utility of Functional Assessment for Teachers of Children with Mental Retardation.

    ERIC Educational Resources Information Center

    Narayan, J.; Myreddi, V.

    1996-01-01

    This study of 42 Indian teachers of students with mental retardation investigated the effectiveness of using a functional assessment checklist for programming in teaching independent living skills. The teachers found the checklist reduced problems in maintaining individualized education programs, was suitable for all levels, and was easy to use.…

  9. Utility of the Functional Assessment Inventory in a Post-Stroke Sample.

    ERIC Educational Resources Information Center

    Heinemann, Allen W.; Crown, Deborah; McMahon, Rita

    2000-01-01

    Examines the validity of using the Functional Assessment Inventory (FAI) in a group of vocational service clients who had suffered from strokes. Findings revealed that with only minor modifications, the FAI was useful for describing participants' vocational potential. The FAI's ability to successfully distinguish stroke subtypes showed that it had…

  10. Modeling earthquake ground motion with an earthquake simulation program (EMPSYN) that utilizes empirical Green's functions

    SciTech Connect

    Hutchings, L.

    1992-01-01

    This report outlines a method of using empirical Green's functions in an earthquake simulation program EMPSYN that provides realistic seismograms from potential earthquakes. The theory for using empirical Green's functions is developed, implementation of the theory in EMPSYN is outlined, and an example is presented where EMPSYN is used to synthesize observed records from the 1971 San Fernando earthquake. To provide useful synthetic ground motion data from potential earthquakes, synthetic seismograms should model frequencies from 0.5 to 15.0 Hz, the full wave-train energy distribution, and absolute amplitudes. However, high-frequency arrivals are stochastically dependent upon the inhomogeneous geologic structure and irregular fault rupture. The fault rupture can be modeled, but the stochastic nature of faulting is largely an unknown factor in the earthquake process. The effect of inhomogeneous geology can readily be incorporated into synthetic seismograms by using small earthquakes to obtain empirical Green's functions. Small earthquakes with source corner frequencies higher than the site recording limit f{sub max}, or much higher than the frequency of interest, effectively have impulsive point-fault dislocation sources, and their recordings are used as empirical Green's functions. Since empirical Green's functions are actual recordings at a site, they include the effects on seismic waves from all geologic inhomogeneities and include all recordable frequencies, absolute amplitudes, and all phases. They scale only in amplitude with differences in seismic moment. They can provide nearly the exact integrand to the representation relation. Furthermore, since their source events have spatial extent, they can be summed to simulate fault rupture without loss of information, thereby potentially computing the exact representation relation for an extended source earthquake.

  11. Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data

    PubMed Central

    Joo, Seongjung; Kawabata, Hugh; Al, Maiwenn J.; Allison, Paul D.; Rutten‐van Mölken, Maureen P. M. H.; Frits, Michelle L.; Iannaccone, Christine K.; Shadick, Nancy A.; Weinblatt, Michael E.

    2016-01-01

    Objective To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study. Methods Other defined thresholds included low disease activity (LDA), moderate (MDA), or severe disease activity (SDA). To control for intraclass correlation and estimate effects of independent variables on outcomes of the modified Health Assessment Questionnaire (M‐HAQ), the EuroQol 5‐domain (EQ‐5D; a quality‐of‐life measure), hospitalization, and durable medical equipment (DME) use, we employed mixed models for continuous outcomes and generalized estimating equations for binary outcomes. Results Among 1,297 subjects, achievement (versus nonachievement) of recommended disease targets was associated with enhanced physical functioning and lower health resource utilization. After controlling for baseline covariates, achievement of disease targets (versus LDA) was associated with significantly enhanced physical functioning based on SDAI ≤3.3 (ΔM‐HAQ −0.047; P = 0.0100) and CDAI ≤2.8 (−0.073; P = 0.0003) but not DAS28‐CRP <2.6 (−0.022; P = 0.1735). Target attainment was associated with significantly improved EQ‐5D (0.022–0.096; P < 0.0030 versus LDA, MDA, or SDA). Patients achieving guideline‐recommended disease targets were 36–45% less likely to be hospitalized (P < 0.0500) and 23–45% less likely to utilize DME (P < 0.0100). Conclusion Attaining recommended target disease‐activity measures was associated with enhanced physical functioning and health‐related quality of life. Some health outcomes were similar in subjects attaining guideline targets versus LDA. Achieving LDA is a worthy clinical objective in some patients. PMID:26238974

  12. The effect of education on regional brain metabolism and its functional connectivity in an aged population utilizing positron emission tomography.

    PubMed

    Kim, Jaeik; Chey, Jeanyung; Kim, Sang-Eun; Kim, Hoyoung

    2015-05-01

    Education involves learning new information and acquiring cognitive skills. These require various cognitive processes including learning, memory, and language. Since cognitive processes activate associated brain areas, we proposed that the brains of elderly people with longer education periods would show traces of repeated activation as increased synaptic connectivity and capillary in brain areas involved in learning, memory, and language. Utilizing positron emission topography (PET), this study examined the effect of education in the human brain utilizing the regional cerebral glucose metabolism rates (rCMRglcs). 26 elderly women with high-level education (HEG) and 26 with low-level education (LEG) were compared with regard to their regional brain activation and association between the regions. Further, graphical theoretical analysis using rCMRglcs was applied to examine differences in the functional network properties of the brain. The results showed that the HEG had higher rCMRglc in the ventral cerebral regions that are mainly involved in memory, language, and neurogenesis, while the LEG had higher rCMRglc in apical areas of the cerebrum mainly involved in motor and somatosensory functions. Functional connectivity investigated with graph theoretical analysis illustrated that the brain of the HEG compared to those of the LEG were overall more efficient, more resilient, and characterized by small-worldness. This may be one of the brain's mechanisms mediating the reserve effects found in people with higher education.

  13. Functional and comparative genomic analyses of an operon involved in fructooligosaccharide utilization by Lactobacillus acidophilus

    PubMed Central

    Barrangou, Rodolphe; Altermann, Eric; Hutkins, Robert; Cano, Raul; Klaenhammer, Todd R.

    2003-01-01

    Lactobacillus acidophilus is a probiotic organism that displays the ability to use prebiotic compounds such as fructooligosaccharides (FOS), which stimulate the growth of beneficial commensals in the gastrointestinal tract. However, little is known about the mechanisms and genes involved in FOS utilization by Lactobacillus species. Analysis of the L. acidophilus NCFM genome revealed an msm locus composed of a transcriptional regulator of the LacI family, a four-component ATP-binding cassette (ABC) transport system, a fructosidase, and a sucrose phosphorylase. Transcriptional analysis of this operon demonstrated that gene expression was induced by sucrose and FOS but not by glucose or fructose, suggesting some specificity for nonreadily fermentable sugars. Additionally, expression was repressed by glucose but not by fructose, suggesting catabolite repression via two cre-like sequences identified in the promoter–operator region. Insertional inactivation of the genes encoding the ABC transporter substrate-binding protein and the fructosidase reduced the ability of the mutants to grow on FOS. Comparative analysis of gene architecture within this cluster revealed a high degree of synteny with operons in Streptococcus mutans and Streptococcus pneumoniae. However, the association between a fructosidase and an ABC transporter is unusual and may be specific to L. acidophilus. This is a description of a previously undescribed gene locus involved in transport and catabolism of FOS compounds, which can promote competition of beneficial microorganisms in the human gastrointestinal tract. PMID:12847288

  14. New functionally dioecious bush tomato from northwestern Australia, Solanum ossicruentum, may utilize "trample burr" dispersal.

    PubMed

    Martine, Christopher T; Cantley, Jason T; Frawley, Emma S; Butler, Alice R; Jordon-Thaden, Ingrid E

    2016-01-01

    A new Australian species of functionally dioecious bush tomato of Solanum subgenus Leptostemonum is described. Solanum ossicruentum Martine & J.Cantley, sp. nov., is thought to be allied with members of the problematic "Dioicum Complex" lineage, but differs in its short silvery indumentum, long calyx lobes, larger stature, and an unusual fruit morphology that may represent "trample burr" seed dispersal. The species occurs in a range extending from the eastern Kimberley in Western Australia to far northwestern Northern Territory and has been recognized for decades as a variant of Solanum dioicum W.Fitzg. Specimens of this species were previously referred to by D.E. Symon and others as Solanum dioicum 'Tanami.' Ex situ crossing studies and SEM images of inaperturate pollen grains produced in morphologically hermaphrodite flowers indicate that this taxon is functionally dioecious. The scientific name was chosen with the help of 150 seventh grade life science students from Pennsylvania, USA. PMID:27489475

  15. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  16. Eddy current nondestructive testing device for measuring variable characteristics of a sample utilizing Walsh functions

    DOEpatents

    Libby, Hugo L.; Hildebrand, Bernard P.

    1978-01-01

    An eddy current testing device for measuring variable characteristics of a sample generates a signal which varies with variations in such characteristics. A signal expander samples at least a portion of this generated signal and expands the sampled signal on a selected basis of square waves or Walsh functions to produce a plurality of signal components representative of the sampled signal. A network combines these components to provide a display of at least one of the characteristics of the sample.

  17. The Nutraceutical Properties of Ovotransferrin and Its Potential Utilization as a Functional Food

    PubMed Central

    Giansanti, Francesco; Leboffe, Loris; Angelucci, Francesco; Antonini, Giovanni

    2015-01-01

    Ovotransferrin or conalbumin belong to the transferrin protein family and is endowed with both iron-transfer and protective activities. In addition to its well-known antibacterial properties, ovotransferrin displays other protective roles similar to those already ascertained for the homologous mammalian lactoferrin. These additional functions, in many cases not directly related to iron binding, are also displayed by the peptides derived from partial hydrolysis of ovotransferrin, suggesting a direct relationship between egg consumption and human health. PMID:26556366

  18. Functionally Diverse Nucleophilic Trapping of Iminium Intermediates Generated Utilizing Visible Light

    PubMed Central

    Freeman, David B.; Furst, Laura; Condie, Allison G.

    2011-01-01

    Our previous studies into visible light-mediated aza-Henry reactions demonstrated that molecular oxygen played a vital role in catalyst turnover as well as the production of base to facilitate the nucleophilic addition of nitroalkanes. Herein, improved conditions for the generation of iminium ions from tetrahydroisoquinolines that allow for versatile nucleophilic trapping are reported. The new conditions provide access to a diverse range of functionality under mild, anaerobic reaction conditions as well as mechanistic insights into the photoredox cycle. PMID:22148974

  19. Functional evidence equating the pharmacologically-defined alpha 1A- and cloned alpha 1C-adrenoceptor: studies in the isolated perfused kidney of rat.

    PubMed Central

    Blue, D. R.; Bonhaus, D. W.; Ford, A. P.; Pfister, J. R.; Sharif, N. A.; Shieh, I. A.; Vimont, R. L.; Williams, T. J.; Clarke, D. E.

    1995-01-01

    1. The present study characterizes and classifies alpha 1-adrenoceptor-mediated vasoconstriction in the isolated perfused kidney of rat using quantitative receptor pharmacology and compares the results to radioligand binding studies (made in cloned alpha 1-adrenoceptor subtypes, native alpha 1A-adrenoceptors in submaxillary gland of rat, and alpha 1A-adrenoceptors in several other tissues of rat). 2. Concentration-effect curves to noradrenaline in the presence of 5-methyl-urapidil were biphasic, indicating alpha 1-adrenoceptor heterogeneity. The alpha 1-adrenoceptor subtype mediating the first phase (low affinity for 5-methyl-urapidil) could not be 'isolated' for detailed pharmacological characterization but was defined by a sensitivity to inhibition by chloroethylclonidine and an inability of methoxamine to activate the site. Additionally, vasoconstriction mediated by this alpha 1-adrenoceptor subtype or subtypes was abolished by nitrendipine (1 microM), thereby allowing characterization of the second, high affinity site for 5-methyl-urapidil. 3. The following antagonists interacted competitively with noradrenaline at the alpha 1-adrenoceptor for which 5-methyl-urapidil exhibits high affinity (pKB value): WB 4101 (10.3) > prazosin (9.5) approximately HV 723 (9.3) approximately 5-methyl-urapidil (9.2) > phenotolamine (8.6) > spiperone (pA2 = 8.1) approximately oxymetazoline (7.9). In contrast, insurmountable antagonism was seen with S(+)- and R(-)-niguldipine, the S(+)-isomer being approximately 30 fold more potent than the R(-)-isomer. Receptor protection experiments indicated that S(+)-niguldipine interacted directly with alpha 1-adrenoceptors. Dehydroniguldipine acted as a competitive antagonist (pKB = 9.0). Thus, the results with antagonists define the alpha 1-adrenoceptor as an alpha 1A-adrenoceptor. 4. An agonist 'fingerprint' was constructed in the presence of nitrendipine to define further the alpha 1A-adrenoceptor. The following order and relativity of

  20. Utilization of Food Processing By-products as Dietary, Functional, and Novel Fiber: A Review.

    PubMed

    Sharma, Satish Kumar; Bansal, Sangita; Mangal, Manisha; Dixit, Anil Kumar; Gupta, Ram K; Mangal, A K

    2016-07-26

    Fast growing food processing industry in most countries across the world, generates huge quantity of by-products, including pomace, hull, husk, pods, peel, shells, seeds, stems, stalks, bran, washings, pulp refuse, press cakes, etc., which have less use and create considerable environmental pollution. With growing interest in health promoting functional foods, the demand of natural bioactives has increased and exploration for new sources is on the way. Many of the food processing industrial by-products are rich sources of dietary, functional, and novel fibers. These by-products can be directly (or after certain modifications for isolation or purification of fiber) used for the manufacture of various foods, i.e. bread, buns, cake, pasta, noodles, biscuit, ice creams, yogurts, cheese, beverages, milk shakes, instant breakfasts, ice tea, juices, sports drinks, wine, powdered drink, fermented milk products, meat products and meat analogues, synthetic meat, etc. A comprehensive literature survey has been carried on this topic to give an overview in the field dietary fiber from food by-products. In this article, the developments in the definition of fiber, fiber classification, potential sources of dietary fibers in food processing by-products, their uses, functional properties, caloric content, energy values and the labelling regulations have been discussed. PMID:25748244

  1. Utilization of Food Processing By-products as Dietary, Functional, and Novel Fiber: A Review.

    PubMed

    Sharma, Satish Kumar; Bansal, Sangita; Mangal, Manisha; Dixit, Anil Kumar; Gupta, Ram K; Mangal, A K

    2016-07-26

    Fast growing food processing industry in most countries across the world, generates huge quantity of by-products, including pomace, hull, husk, pods, peel, shells, seeds, stems, stalks, bran, washings, pulp refuse, press cakes, etc., which have less use and create considerable environmental pollution. With growing interest in health promoting functional foods, the demand of natural bioactives has increased and exploration for new sources is on the way. Many of the food processing industrial by-products are rich sources of dietary, functional, and novel fibers. These by-products can be directly (or after certain modifications for isolation or purification of fiber) used for the manufacture of various foods, i.e. bread, buns, cake, pasta, noodles, biscuit, ice creams, yogurts, cheese, beverages, milk shakes, instant breakfasts, ice tea, juices, sports drinks, wine, powdered drink, fermented milk products, meat products and meat analogues, synthetic meat, etc. A comprehensive literature survey has been carried on this topic to give an overview in the field dietary fiber from food by-products. In this article, the developments in the definition of fiber, fiber classification, potential sources of dietary fibers in food processing by-products, their uses, functional properties, caloric content, energy values and the labelling regulations have been discussed.

  2. Utility of the ISTH bleeding assessment tool in predicting platelet defects in participants with suspected inherited platelet function disorders

    PubMed Central

    Lowe, G C; Lordkipanidzé, M; Watson on behalf of the uk gapp study group, S P

    2013-01-01

    Background The ISTH bleeding assessment tool (ISTH-BAT) was developed to record bleeding symptoms and to aid diagnosis in patients with a possible bleeding disorder. Objectives To investigate the utility of the ISTH-BAT in predicting functional defects in platelet activation in participants with suspected inherited platelet function disorders. Patients/Methods Participants with clinical evidence of excessive bleeding and suspected inherited platelet function disorders and healthy volunteers were recruited to the Genotyping and Phenotyping of Platelets study (GAPP; ISRCTN 77951167). The ISTH-BAT questionnaire was applied by a trained investigator prior to lumiaggregometry. Results One hundred participants were included (79 with suspected inherited platelet function disorders, and 21 healthy volunteers). The ISTH-BAT score in participants with suspected inherited platelet function disorders (median 12; interquartile range [IQR] 8–16) was significantly higher than in healthy volunteers (median 0; IQR 0–0). There was no difference between participants with suspected inherited platelet function disorders with a platelet defect detected by lumiaggregometry (median 11; IQR 8–16) and those with normal platelet function (median 12; IQR 8–14) (P > 0.05). The ISTH-BAT score was not associated with a demonstrable platelet defect on platelet function testing (area under the receiver operating characteristic curve = 0.501 [95% confidence interval 0.372–0.630, P = 0.98] and odds ratio 1.01 [95% confidence interval 0.93–1.09, P = 0.91]). Conclusions The ISTH-BAT is a powerful tool for documenting lifelong bleeding history. However, the score obtained is not predictive of the presence of a platelet defect on lumiaggregometry in patients with suspected inherited platelet function disorders. PMID:23809206

  3. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium.

    PubMed

    Williams, Baraka S; Isokpehi, Raphael D; Mbah, Andreas N; Hollman, Antoinesha L; Bernard, Christina O; Simmons, Shaneka S; Ayensu, Wellington K; Garner, Bianca L

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  4. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium

    PubMed Central

    Williams, Baraka S.; Isokpehi, Raphael D.; Mbah, Andreas N.; Hollman, Antoinesha L.; Bernard, Christina O.; Simmons, Shaneka S.; Ayensu, Wellington K.; Garner, Bianca L.

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  5. [The secretory function of skeletal muscles and its role in energy metabolism and utilization].

    PubMed

    Halmos, Tamás; Suba, Ilona

    2014-09-14

    It is well-known for a long-time, that intensive exercise is favourable for many metabolic parameters. Up-till now the exact mechanism has not been clarified. Recently it has turned out, that the muscular system is an extended endocrine organ, which, during contraction, secretes many hundred peptides, so called adipomyokines into the blood stream. Many of them improve glucose-utilization of the muscular system, and insulin-sensitivity, via endocrine, paracrine, or autocrine pathways. Worldwide intensive research takes place to clear up the exact pathomechanism of these processes. It came to light: 1. The newly discovered adipomyokine, irisin induces "browning" of beige precursor fat-cells, which are present in white adipose tissue. The developed beige adipose tissue by this way disposes with the advantegous properties of the brown adipose tissue. Taking together these facts, irisin might be a therapeutic choice in treating certain diseases, caused by inactive life-style. 2. Therapeutic application of brown adipose tissue in obesity, metabolic syndrome, and type 2 diabetes seems to be successful. This mechanism is based on removal of unnecessary calories via thermogenesis. 3. The role of myostatin, which is also produced by muscle contraction, is contradictory. It is not clear, why does the muscle system produce damaging product for the metabolism. On the other hand, inhibition of myostatin might be a therapeutic option. It is still questionable, whether the other hundreds of myokines could possess practicable roles on glucose, lipid, insulin secretion/effects. At present one can establish, that regular exercise is essential for the everyday practise, in order to optimise quality of life. PMID:25194869

  6. [The secretory function of skeletal muscles and its role in energy metabolism and utilization].

    PubMed

    Halmos, Tamás; Suba, Ilona

    2014-09-14

    It is well-known for a long-time, that intensive exercise is favourable for many metabolic parameters. Up-till now the exact mechanism has not been clarified. Recently it has turned out, that the muscular system is an extended endocrine organ, which, during contraction, secretes many hundred peptides, so called adipomyokines into the blood stream. Many of them improve glucose-utilization of the muscular system, and insulin-sensitivity, via endocrine, paracrine, or autocrine pathways. Worldwide intensive research takes place to clear up the exact pathomechanism of these processes. It came to light: 1. The newly discovered adipomyokine, irisin induces "browning" of beige precursor fat-cells, which are present in white adipose tissue. The developed beige adipose tissue by this way disposes with the advantegous properties of the brown adipose tissue. Taking together these facts, irisin might be a therapeutic choice in treating certain diseases, caused by inactive life-style. 2. Therapeutic application of brown adipose tissue in obesity, metabolic syndrome, and type 2 diabetes seems to be successful. This mechanism is based on removal of unnecessary calories via thermogenesis. 3. The role of myostatin, which is also produced by muscle contraction, is contradictory. It is not clear, why does the muscle system produce damaging product for the metabolism. On the other hand, inhibition of myostatin might be a therapeutic option. It is still questionable, whether the other hundreds of myokines could possess practicable roles on glucose, lipid, insulin secretion/effects. At present one can establish, that regular exercise is essential for the everyday practise, in order to optimise quality of life.

  7. Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate.

    PubMed

    Yajamanam, Naresh; Vinapamula, Kiranmayi S; Sivakumar, V; Bitla, Aparna R; Rao, P V L N Srinivasa

    2016-03-01

    Diagnosis of renal diseases by assessing renal parameters in saliva. Biochemical investigations using serum form important component of monitoring patients with renal disease. Utility of saliva, in diagnosis and monitoring of patients with renal disease and for calculation of estimated glomerular filtration rate (eGFR), was studied. Sixty patients with renal disease and sixty ageand sex-matched healthy controls were studied. Urea, creatinine, sodium, potassium, uric acid, calcium, and phosphorus were measured in both serum and saliva. eGFR was calculated using salivary creatinine. Data were expressed as mean ± standard deviation. Comparison and correlation between groups were assessed by Student's t-test and Pearson correlation, respectively. Bland-Altman plot, mountain plot, and intra-class correlation coefficient were used to test agreement. A P <0.05 was considered statistically significant. Statistical analysis was done using Microsoft excel spreadsheets, Medcalc Version 10.0, and SPSS version 11.5. Salivary levels of urea, creatinine, uric acid, sodium, potassium, and phosphorus were higher in patients compared to controls. Potassium and phosphorus levels were higher (P = 0.001) and creatinine, sodium, calcium, and uric acid levels were lower (P = 0.001) in saliva compared to serum in both patients and controls. Positive correlation was observed between serum and salivary urea and creatinine (P < 0.0001). eGFR values calculated from salivary creatinine showed good agreement with those calculated form serum creatinine. Salivary urea (>6 mmol/L) and creatinine (>14.6 μmol/L) and eGFR calculated from salivary creatinine can be used to identify patients with renal disease.

  8. Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

    2006-01-01

    Space flight induces adaptive modification in sensorimotor function, allowing crewmembers to operate in the unique microgravity environment. This adaptive state, however, is inappropriate for a terrestrial environment. During a re-adaptation period upon their return to Earth, crewmembers experience alterations in sensorimotor function, causing various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Following long duration space flight, sensorimotor dysfunction would prevent or extend the time required to make an emergency egress from the vehicle; compromising crew safety and mission objectives. We are investigating two types of motor learning that may interact with each other and influence a crewmember's ability to re-adapt to Earth's gravity environment. In strategic learning, crewmembers make rapid modifications in their motor control strategy emphasizing error reduction. This type of learning may be critical during the first minutes and hours after landing. In adaptive learning, long-term plastic transformations occur, involving morphological changes and synaptic modification. In recent literature these two behavioral components have been associated with separate brain structures that control the execution of motor strategies: the strategic component was linked to the posterior parietal cortex and the adaptive component was linked to the cerebellum (Pisella, et al. 2004). The goal of this paper was to demonstrate the relative contributions of the strategic and adaptive components to the re-adaptation process in locomotor control after long duration space flight missions on the International Space Station (ISS). The Functional Mobility Test (FMT) was developed to assess crewmember s ability to ambulate postflight from an operational and functional perspective. Sixteen crewmembers were tested preflight (3 sessions) and postflight (days 1, 2, 4, 7, 25) following a long duration space flight (approx 6 months) on the ISS. We

  9. Real-time Periodic Processing of RT-middleware Utilizing Linux Standard Functionalities

    NASA Astrophysics Data System (ADS)

    Shimizu, Masaharu; Toda, Kengo; Hayashibara, Yasuo; Yamato, Hideaki; Furuta, Takayuki

    A new methodology of real-time periodic processing on RT-middleware based on the Linux standard functionalities is presented in this paper. The central of discussion is on the realization of real-time processing while keeping the reusability of software modules ensured by the RT-middleware framework as well as the portability provided by the Linux development mainstream. In order to show the validity of the proposed approach, two robot systems, including an omnidirectional electric wheelchair steered by haptic joystick, are presented and the discussion about the evaluation result follows from the view point of practicality.

  10. Study on utility of an approximated transfer function of dynamically tuned dry gyro

    NASA Astrophysics Data System (ADS)

    Shingu, H.; Otsuki, M.; Hayano, T.

    The use of a dry gyro in analog rebalance loops is described and a method to improve the static and dynamic characteristics is presented. The transfer function is derived by transforming a generalized equation into the approximated form based on the design specifications of the mechanical parts. This approximation is proved to be reasonable by the result that the differences between the numerical solutions of a generalized equation and those of an approximated equation are less than 1.0%, and their mean values are less than 0.003%. Noninteracting control is analyzed and the stability conditions are investigated. A fundamental design conception for rebalance loops was established.

  11. The Predictive Utility of Early Childhood Disruptive Behaviors for School-Age Social Functioning

    PubMed Central

    Shaw, Daniel S.; Dishion, Thomas J.; Wilson, Melvin N.

    2016-01-01

    Research suggests that school-age children with disruptive behavior (DB) problems frequently demonstrate impaired social skills and experience rejection from peers, which plays a crucial role in the pathway to more serious antisocial behavior. A critical question is which DB problems in early childhood are prognostic of impaired social functioning in school-age children. This study examines the hypothesis that aggression in early childhood will be the more consistent predictor of compromised social functioning than inattentive, hyperactive-impulsive, or oppositional behavior. Participants included an ethnically diverse sample of 725 high-risk children from 3 geographically distinct areas followed from ages 2 to 8.5. Four latent growth models of DB from child ages 2 to 5, and potential interactions between dimensions, were used to predict latent parent and teacher ratings of school-age social dysfunction. Analyses were conducted in a multi-group format to examine potential differences between intervention and control group participants. Results showed that age 2 aggression was the DB problem most consistently associated with both parent- and teacher-rated social dysfunction for both groups. Early starting aggressive behavior may be particularly important for the early identification of children at risk for school-age social difficulties. PMID:25526865

  12. Utilizing systems biology to unravel stomatal function and the hierarchies underpinning its control.

    PubMed

    Medeiros, David B; Daloso, Danilo M; Fernie, Alisdair R; Nikoloski, Zoran; Araújo, Wagner L

    2015-08-01

    Stomata control the concomitant exchange of CO2 and transpiration in land plants. While a constant supply of CO2 is need to maintain the rate of photosynthesis, the accompanying water losses must be tightly regulated to prevent dehydration and undesired metabolic changes. The factors affecting stomatal movement are directly coupled with the cellular networks of guard cells. Although the guard cell has been used as a model for characterization of signaling pathways, several important questions about its functioning remain elusive. Current modeling approaches describe the stomatal conductance in terms of relatively few easy-to-measure variables being unsuitable for in silico design of genetic manipulation strategies. Here, we argue that a system biology approach, combining modeling and high-throughput experiments, may be used to elucidate the mechanisms underlying stomata control and to determine targets for modulation of stomatal responses to environment. In support of our opinion, we review studies demonstrating how high-throughput approaches have provided a systems-view of guard cells. Finally, we emphasize the opportunities and challenges of genome-scale modeling and large-scale data integration for in silico manipulation of guard cell functions to improve crop yields, particularly under stress conditions which are of pertinence both to climate change and water use efficiency. PMID:25689387

  13. CHARACTERISTICS OF BORDERLINE PERSONALITY DISORDER IN A COMMUNITY SAMPLE: COMORBIDITY, TREATMENT UTILIZATION, AND GENERAL FUNCTIONING

    PubMed Central

    Tomko, Rachel L.; Trull, Timothy J.; Wood, Phillip K.; Sher, Kenneth J.

    2013-01-01

    This study provides estimates of the prevalence and demographic features of borderline personality disorder (BPD) in a community sample as well as BPD comorbidity rates with Axis I and II disorders. In addition, the authors provide data on general functioning and treatment seeking among individuals with BPD. Data from 34,481 participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analyzed. Results suggest that 2.7% of adults in the United States meet diagnostic criteria for BPD, with slightly higher rates of the disorder in females, people in lower income brackets, people younger than 30, and individuals who are separated or divorced. Racial/ethnic differences were evident, with Native Americans (5.0%) and Blacks (3.5%) having significantly higher rates of the disorder, on average, and Asians having significantly lower rates (1.2%). Individuals with a BPD diagnosis were likely to have co-occurring lifetime mood disorders, anxiety disorders, substance use disorders, and other personality disorders. Specifically, 84.8% of individuals with BPD also had a lifetime anxiety disorder, 82.7% had a lifetime mood disorder/episode, and 78.2% were diagnosed with a lifetime substance use disorder. Individuals with BPD showed significant impairment in functioning and were highly likely to seek therapy or receive medication for mental health concerns. PMID:25248122

  14. World Climate Classification and Search: Data Mining Approach Utilizing Dynamic Time Warping Similarity Function

    NASA Astrophysics Data System (ADS)

    Stepinski, T. F.; Netzel, P.; Jasiewicz, J.

    2014-12-01

    We have developed a novel method for classification and search of climate over the global land surface excluding Antarctica. Our method classifies climate on the basis of the outcome of time series segmentation and clustering. We use WorldClim 30 arc sec. (approx. 1 km) resolution grid data which is based on 50 years of climatic observations. Each cell in a grid is assigned a 12 month series consisting of 50-years monthly averages of mean, maximum, and minimum temperatures as well as the total precipitation. The presented method introduces several innovations with comparison to existing data-driven methods of world climate classifications. First, it uses only climatic rather than bioclimatic data. Second, it employs object-oriented methodology - the grid is first segmented before climatic segments are classified. Third, and most importantly, the similarity between climates in two given cells is performed using the dynamic time warping (DTW) measure instead of the Euclidean distance. The DTW is known to be superior to Euclidean distance for time series, but has not been utilized before in classification of global climate. To account for computational expense of DTW we use highly efficient GeoPAT software (http://sil.uc.edu/gitlist/) that, in the first step, segments the grid into local regions of uniform climate. In the second step, the segments are classified. We also introduce a climate search - a GeoWeb-based method for interactive presentation of global climate information in the form of query-and-retrieval. A user selects a geographical location and the system returns a global map indicating level of similarity between local climates and a climate in the selected location. The results of the search for location: "University of Cincinnati, Main Campus" are presented on attached map. The results of the search for location: "University of Cincinnati, Main Campus" are presented on the map. We have compared the results of our method to Koeppen classification scheme

  15. Utilization of Modified NFL Combine Testing to Identify Functional Deficits in Athletes Following ACL Reconstruction

    PubMed Central

    MYER, GREGORY D.; SCHMITT, LAURA C.; BRENT, JENSEN L.; FORD, KEVIN R.; BARBER FOSS, KIM D.; SCHERER, BRADLEY J.; HEIDT, ROBERT S.; DIVINE, JON G.; HEWETT, TIMOTHY E.

    2012-01-01

    STUDY DESIGN Case control. OBJECTIVES To use modified NFL Combine testing methodology to test for functional deficits in athletes following anterior cruciate ligament (ACL) reconstruction following return to sport. BACKGROUND There is a need to develop objective, performance-based, on-field assessment methods designed to identify potential lower extremity performance deficits and related impairments in this population. METHODS Eighteen patients (mean ± SD age, 16.9 ± 2.1 years; height, 170.0 ± 8.7 cm; body mass, 71.9 ± 21.8 kg) who returned to their sport within a year following ACL reconstruction (95% CI: 7.8 to 11.9 months from surgery) participated (ACLR group). These individuals were asked to bring 1 or 2 teammates to serve as control participants, who were matched for sex, sport, and age (n = 20; mean ± SD age, 16.9 ± 1.1 years; height, 169.7 ± 8.4 cm; body mass, 70.1 ± 20.7 kg). Functional performance was tested using the broad jump, vertical jump, modified long shuttle, modified pro shuttle, modified agility T-test, timed hop, triple hop, single hop, and crossover hop tests. A 1-way multivariate analysis of variance (MANOVA) was used to evaluate group differences for dependent performance variables. RESULTS The functional performance measurements of skills requiring bilateral involvement of both lower extremities showed no group differences between the ACLR and control groups (P>.05). An overall group difference (P = .006) was observed for the combined limb symmetry index (LSI) measures. However, the modified double-limb performance tasks (long shuttle, modified agility T-test, and pro shuttle) were not, independently, sufficiently sensitive to detect limb deficits in individuals with ACL reconstruction. Conversely, the LSI on the distance measures of the single-limb performance tasks all provided moderate to large effect sizes to differentiate between the ACLR and control groups, as the individuals who had ACL reconstruction demonstrated involved

  16. Utility of functional imaging in prediction or assessment of treatment response and prognosis following thermotherapy

    PubMed Central

    Dewhirst, Mark W.; Thrall, Donald E.; Palmer, Gregory; Schroeder, Thies; Vujaskovic, Zeljko; Charles, H. Cecil; MacFall, James; Wong, Terence

    2009-01-01

    The purpose of this review is to examine the roles that functional imaging may play in prediction of treatment response and determination of overall prognosis in patients who are enrolled in thermotherapy trials, either in combination with radiotherapy, chemotherapy or both. Most of the historical work that has been done in this field has focused on MRI/MRS methods, so the emphasis will be there, although some discussion of the role that PET might play will also be examined. New optical technologies also hold promise for obtaining low cost, yet valuable physiologic data from optically accessible sites. The review is organized by traditional outcome parameters: local response, local control and progression free or overall survival. Included in the review is a discussion of future directions for this type of translational work. PMID:20170362

  17. Risk aversion and uncertainty in cost-effectiveness analysis: the expected-utility, moment-generating function approach.

    PubMed

    Elbasha, Elamin H

    2005-05-01

    The availability of patient-level data from clinical trials has spurred a lot of interest in developing methods for quantifying and presenting uncertainty in cost-effectiveness analysis (CEA). Although the majority has focused on developing methods for using sample data to estimate a confidence interval for an incremental cost-effectiveness ratio (ICER), a small strand of the literature has emphasized the importance of incorporating risk preferences and the trade-off between the mean and the variance of returns to investment in health and medicine (mean-variance analysis). This paper shows how the exponential utility-moment-generating function approach is a natural extension to this branch of the literature for modelling choices from healthcare interventions with uncertain costs and effects. The paper assumes an exponential utility function, which implies constant absolute risk aversion, and is based on the fact that the expected value of this function results in a convenient expression that depends only on the moment-generating function of the random variables. The mean-variance approach is shown to be a special case of this more general framework. The paper characterizes the solution to the resource allocation problem using standard optimization techniques and derives the summary measure researchers need to estimate for each programme, when the assumption of risk neutrality does not hold, and compares it to the standard incremental cost-effectiveness ratio. The importance of choosing the correct distribution of costs and effects and the issues related to estimation of the parameters of the distribution are also discussed. An empirical example to illustrate the methods and concepts is provided.

  18. Building Efficient Comparative Effectiveness Trials through Adaptive Designs, Utility Functions, and Accrual Rate Optimization: Finding the Sweet Spot

    PubMed Central

    Gajewski, Byron J.; Berry, Scott M.; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen; Herbelin, Laura; Barohn, Richard

    2014-01-01

    The time is right for the use of Bayesian Adaptive Designs (BAD) in comparative effectiveness trials. For example, PCORI has joined the FDA and NIH in adopting policies/guidelines encouraging their use. There are multiple aspects to BAD that need to be considered when designing a comparative effectiveness design. First, the adaptation rules can determine the expected size of the trial. Second, a utility function can be used to combine extremely important co-endpoints (e.g. efficacy and tolerability), and is a valuable tool for incorporating clinical expertise and potentially patient preference. Third, accrual rate is also very, very important. Specifically, there is a juxtaposition related to accrual and BAD. If accrual rate is too fast we never gain efficient information for adapting. If accrual rate is too slow we never finish the clinical trial. We propose methodology for finding the “sweet spot” for BAD that addresses these as design parameters. We demonstrate the methodology on a comparative effectiveness BAD of pharmaceutical agents in cryptogenic sensory polyneuropathy (CSPN). The study has five arms with two endpoints that are combined with a utility function. The accrual rate is assumed to stem from multiple sites. We perform simulations from which the composite accrual rates across sites results in various piecewise Poisson distributions as parameter inputs. We balance both average number of patients needed and average length of time to finish the study. PMID:25640114

  19. Building efficient comparative effectiveness trials through adaptive designs, utility functions, and accrual rate optimization: finding the sweet spot.

    PubMed

    Gajewski, Byron J; Berry, Scott M; Quintana, Melanie; Pasnoor, Mamatha; Dimachkie, Mazen; Herbelin, Laura; Barohn, Richard

    2015-03-30

    The time is right for the use of Bayesian Adaptive Designs (BAD) in comparative effectiveness trials. For example, Patient Centered Outcomes Research Institute has joined the Food and Drug Administration and National Intitutes of Health in adopting policies/guidelines encouraging their use. There are multiple aspects to BAD that need to be considered when designing a comparative effectiveness design. First, the adaptation rules can determine the expected size of the trial. Second, a utility function can be used to combine extremely important co-endpoints (e.g., efficacy and tolerability) and is a valuable tool for incorporating clinical expertise and potentially patient preference. Third, accrual rate is also very, very important. Specifically, there is a juxtaposition related to accrual and BAD. If accrual rate is too fast we never gain efficient information for adapting. If accrual rate is too slow we never finish the clinical trial. We propose methodology for finding the 'sweet spot' for BAD that addresses these as design parameters. We demonstrate the methodology on a comparative effectiveness BAD of pharmaceutical agents in cryptogenic sensory polyneuropathy. The study has five arms with two endpoints that are combined with a utility function. The accrual rate is assumed to stem from multiple sites. We perform simulations from which the composite accrual rates across sites result in various piecewise Poisson distributions as parameter inputs. We balance both average number of patients needed and average length of time to finish the study.

  20. A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing.

    PubMed

    Stiffler, Michael A; Subramanian, Subu K; Salinas, Victor H; Ranganathan, Rama

    2016-01-01

    Site-directed mutagenesis has long been used as a method to interrogate protein structure, function and evolution. Recent advances in massively-parallel sequencing technology have opened up the possibility of assessing the functional or fitness effects of large numbers of mutations simultaneously. Here, we present a protocol for experimentally determining the effects of all possible single amino acid mutations in a protein of interest utilizing high-throughput sequencing technology, using the 263 amino acid antibiotic resistance enzyme TEM-1 β-lactamase as an example. In this approach, a whole-protein saturation mutagenesis library is constructed by site-directed mutagenic PCR, randomizing each position individually to all possible amino acids. The library is then transformed into bacteria, and selected for the ability to confer resistance to β-lactam antibiotics. The fitness effect of each mutation is then determined by deep sequencing of the library before and after selection. Importantly, this protocol introduces methods which maximize sequencing read depth and permit the simultaneous selection of the entire mutation library, by mixing adjacent positions into groups of length accommodated by high-throughput sequencing read length and utilizing orthogonal primers to barcode each group. Representative results using this protocol are provided by assessing the fitness effects of all single amino acid mutations in TEM-1 at a clinically relevant dosage of ampicillin. The method should be easily extendable to other proteins for which a high-throughput selection assay is in place. PMID:27403811

  1. Utilization of inherent miRNAs in functional analyses of Toxoplasma gondii genes.

    PubMed

    Crater, Anna K; Manni, Emad; Ananvoranich, Sirinart

    2015-01-01

    MicroRNAs (miRNAs) are crucial genetic effectors partaking in numerous mechanisms of gene regulation in eukaryotic organisms. Recent discoveries of miRNA in Toxoplasma gondii, an intracellular obligate parasite of the phylum Apicomplexa, suggested possible roles of T. gondii miRNAs (Tg-miRNAs) in the post-transcriptional gene regulation and in the cell biology of the parasite. To gain a better understanding of the involvement of Tg-miRNAs in regulating the parasite gene expression, a dual luciferase reporter system was used in the examination and evaluation of the effects of endogenous Tg-miRNAs, their mimics and inhibitors. A Renilla luciferase (Rnluc) transcript was engineered to carry independent binding sites of two abundant species, namely Tg-miR-60a and Tg-miR-4a, so that the expression of Rnluc was silenced in a sequence specific manner by Tg-miR-60a and Tg-miR-4a. Notably, Tg-miR-60a, but not Tg-miR-4a, caused the levels of Rnluc transcripts to decrease. These findings strongly suggested that T. gondii employs the Tg-miRNA species-specific mode of silencing actions: transcript degradation by Tg-miR-60a, and translational suppression by Tg-miR-4a. Herein we developed a genetic system that exploits and directs the most abundant Tg-miR-60a for loss-of-function analyses in T. gondii. As a proof of principle, we showed that when the binding sites for Tg-miR-60a were introduced into the parasite transcripts via homologous recombination at the locus of (i) DEAD-box RNA helicase (TgHoDI), or (ii) lactate dehydrogenase isoform 1 (TgLDH1), the expression levels of the selected genes can be altered. It was thus proven that inherit Tg-miR-60a could be directed and used to assist in the loss-of-function analyses.

  2. Defining periodontal health

    PubMed Central

    2015-01-01

    Assessment of the periodontium has relied exclusively on a variety of physical measurements (e.g., attachment level, probing depth, bone loss, mobility, recession, degree of inflammation, etc.) in relation to various case definitions of periodontal disease. Periodontal health was often an afterthought and was simply defined as the absence of the signs and symptoms of a periodontal disease. Accordingly, these strict and sometimes disparate definitions of periodontal disease have resulted in an idealistic requirement of a pristine periodontium for periodontal health, which makes us all diseased in one way or another. Furthermore, the consequence of not having a realistic definition of health has resulted in potentially questionable recommendations. The aim of this manuscript was to assess the biological, environmental, sociological, economic, educational and psychological relationships that are germane to constructing a paradigm that defines periodontal health using a modified wellness model. The paradigm includes four cardinal characteristics, i.e., 1) a functional dentition, 2) the painless function of a dentition, 3) the stability of the periodontal attachment apparatus, and 4) the psychological and social well-being of the individual. Finally, strategies and policies that advocate periodontal health were appraised. I'm not sick but I'm not well, and it's a sin to live so well. Flagpole Sitta, Harvey Danger PMID:26390888

  3. DTI measures track and predict motor function outcomes in stroke rehabilitation utilizing BCI technology.

    PubMed

    Song, Jie; Nair, Veena A; Young, Brittany M; Walton, Leo M; Nigogosyan, Zack; Remsik, Alexander; Tyler, Mitchell E; Farrar-Edwards, Dorothy; Caldera, Kristin E; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2015-01-01

    Tracking and predicting motor outcomes is important in determining effective stroke rehabilitation strategies. Diffusion tensor imaging (DTI) allows for evaluation of the underlying structural integrity of brain white matter tracts and may serve as a potential biomarker for tracking and predicting motor recovery. In this study, we examined the longitudinal relationship between DTI measures of the posterior limb of the internal capsule (PLIC) and upper-limb motor outcomes in 13 stroke patients (median 20-month post-stroke) who completed up to 15 sessions of intervention using brain-computer interface (BCI) technology. Patients' upper-limb motor outcomes and PLIC DTI measures including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were assessed longitudinally at four time points: pre-, mid-, immediately post- and 1-month-post intervention. DTI measures and ratios of each DTI measure comparing the ipsilesional and contralesional PLIC were correlated with patients' motor outcomes to examine the relationship between structural integrity of the PLIC and patients' motor recovery. We found that lower diffusivity and higher FA values of the ipsilesional PLIC were significantly correlated with better upper-limb motor function. Baseline DTI ratios were significantly correlated with motor outcomes measured immediately post and 1-month-post BCI interventions. A few patients achieved improvements in motor recovery meeting the minimum clinically important difference (MCID). These findings suggest that upper-limb motor recovery in stroke patients receiving BCI interventions relates to the microstructural status of the PLIC. Lower diffusivity and higher FA measures of the ipsilesional PLIC contribute toward better motor recovery in the stroke-affected upper-limb. DTI-derived measures may be a clinically useful biomarker in tracking and predicting motor recovery in stroke patients receiving BCI interventions.

  4. Multistep Lattice-Voxel method utilizing lattice function for Monte-Carlo treatment planning with pixel based voxel model.

    PubMed

    Kumada, H; Saito, K; Nakamura, T; Sakae, T; Sakurai, H; Matsumura, A; Ono, K

    2011-12-01

    Treatment planning for boron neutron capture therapy generally utilizes Monte-Carlo methods for calculation of the dose distribution. The new treatment planning system JCDS-FX employs the multi-purpose Monte-Carlo code PHITS to calculate the dose distribution. JCDS-FX allows to build a precise voxel model consisting of pixel based voxel cells in the scale of 0.4×0.4×2.0 mm(3) voxel in order to perform high-accuracy dose estimation, e.g. for the purpose of calculating the dose distribution in a human body. However, the miniaturization of the voxel size increases calculation time considerably. The aim of this study is to investigate sophisticated modeling methods which can perform Monte-Carlo calculations for human geometry efficiently. Thus, we devised a new voxel modeling method "Multistep Lattice-Voxel method," which can configure a voxel model that combines different voxel sizes by utilizing the lattice function over and over. To verify the performance of the calculation with the modeling method, several calculations for human geometry were carried out. The results demonstrated that the Multistep Lattice-Voxel method enabled the precise voxel model to reduce calculation time substantially while keeping the high-accuracy of dose estimation.

  5. Illness-specific anxiety: implications for functioning and utilization of medical services in adolescents with inflammatory bowel disease.

    PubMed

    Reigada, Laura C; Bruzzese, Jean-Marie; Benkov, Keith J; Levy, Joseph; Waxman, Amanda R; Petkova, Eva; Warner, Carrie Masia

    2011-07-01

    PURPOSE. Adolescents with inflammatory bowel disease (IBD) may be at heightened risk for developing anxiety and depression. This cross-sectional pilot study examined the relationship between anxiety and depression and health-related behaviors. METHODS. Thirty-six adolescents with diagnosed IBD, ages 12-17, and their parents were recruited from two pediatric gastroenterology medical centers. RESULTS. Clinical levels of anxiety (22%) and depressive symptoms (30%) were reported by patients. Regression analyses revealed that IBD-specific anxiety was significantly associated with greater utilization of medical services and worsened psychosocial functioning. PRACTICE IMPLICATIONS. Results provide preliminary support that IBD-specific anxiety may play an important role in disease management, yet concerns are rarely systematically assessed by health professionals.

  6. Ensuring clinical utility and function in a large scale national project in Australia by embedding clinical informatics into design.

    PubMed

    Pearce, Christopher; Macdougall, Cecily; Bainbridge, Michael; Davidson, Jane

    2013-01-01

    Across the globe, healthcare delivery is being transformed by electronic sharing of health information. Such large scale health projects with a national focus are a challenge to design and implement. Delivering clinical outcomes in the context of policy, technical, and design environments represents a particular challenge. On July 1, 2012, Australia delivered the first stage of a personally controlled electronic health record - a national program for sharing a variety of health information between health professionals and between health professionals and consumers. As build of the system commenced, deficiencies of the traditional stakeholder consultation model were identified and replaced by a more structured approach, called clinical functional assurance. Utilising clinical scenarios linked to detailed design requirements, a team of clinicians certified clinical utility at implementation and release points.

  7. Functional Characterization of a Novel Marine Microbial GDSL Lipase and Its Utilization in the Resolution of (±)-1-Phenylethanol.

    PubMed

    Deng, Dun; Zhang, Yun; Sun, Aijun; Liang, Jiayuan; Hu, Yunfeng

    2016-04-01

    A novel GDSL lipase (MT6) was cloned from the genome of Marinactinospora thermotolerans SCSIO 00652 identified from the South China Sea. MT6 showed its maximum identity of 59 % with a putative lipase from Nocardiopsis dassonville. MT6 was heterologously expressed in E. coli BL21(DE3) and further functionally characterized. MT6 could efficiently resolve racemic 1-phenylethanol and generate (R)-1-phenylethanol with high enantiomeric excess (99 %) and conversion rate (54 %) through transesterification reactions after process optimization. Our report was the first one report about the utilization of one GDSL lipase in the preparation of chiral chemicals by transesterification reactions, and the optical selectivity of MT6 was interestingly opposite to those of other common lipases. GDSL lipases represented by MT6 possess great potential for the generation of valuable chiral chemicals in industry.

  8. Functional Characterization of a Novel Dactylosporangium Esterase and Its Utilization in the Asymmetric Synthesis of (R)-Methyl Mandelate.

    PubMed

    Deng, Dun; Zhang, Yun; Sun, Aijun; Hu, Yunfeng

    2016-09-01

    One novel esterase DAEst6 was identified from the genome of Dactylosporangium aurantiacum subsp. Hamdenensis NRRL 18085. DAEst6 was further characterized to be an esterase which exhibited high resistance to high pH values. Esterase DAEst6 could resolve racemic methyl mandelate and generate (R)-methyl mandelate, one key drug intermediate, with an enantiomeric excess and a conversion of 99 and 49 %, respectively, after process optimization. The optimal working condition for the preparation of (R)-methyl mandelate through DAEst6 was found to be 10-mM racemic methyl mandelate, no organic co-solvents, pH 7.5, and 40 °C, for 5 h. Our work was the first report about the functional characterization of one novel Dactylosporangium esterase and the utilization of one Dactylosporangium esterase in kinetic resolution. Dactylosporangium esterases represented by DAEst6 possess great potential in the generation of valuable chiral drug intermediates and chemicals.

  9. Defining critical thoughts.

    PubMed

    Lovatt, Abbie

    2014-05-01

    Nursing education has long struggled to define critical thinking and explain how the process of critical thinking fits into the context of nursing. Despite this long time struggle, nurses and nurse educators continue to strive to foster critical thinking skills in nursing students as intuitively most nurses believe that critical thinking is necessary to function competently in the workplace. This article explores the most recent work of Dr. Stephen Brookfield and ties the concepts which are explored in Brookfield's work to nursing practice. Brookfield identifies that learners understand the meaning of critical thinking the best when the process is first demonstrated. Role modeling is a method educators can use to demonstrate critical thinking and is a strategy which nurses often use in the clinical area to train and mentor new nursing staff. Although it is not a new strategy in nursing education, it is a valuable strategy to engage learners in critical thinking activities. PMID:24418065

  10. Defining clinical 'workstation'.

    PubMed

    Safran, C

    1994-01-01

    Interest in the physician's workstation has increased, yet often seems to focus on technological issues. At Boston's Beth Israel Hospital, the Center for Clinical Computing includes heavily used clinical workstations. Their evolution over the past 20 years suggests design criteria: the workstation must be patient-centered, the interface must be uniform, and data acquisition must be addressed at a system level. However, it is clinical function that really defines a workstation. The workstation should do the following: display patient information rapidly and flexibly; assist with administrative tasks; facilitate communication; and provide four important types of decision support: access to literature, access to databases, clinical calculation, and 'synthetic vision,' or different views of patient data. The solutions to our healthcare problems are not in 'workboxes' we can buy, but in creative approaches we can imagine. We need a patient-centered infrastructure and a reduced workload for the clinician-perhaps a 'worklesstation'. PMID:8125637

  11. The monitoring of gene functions on a cell-defined siRNA microarray in human bone marrow stromal and U2OS cells

    PubMed Central

    Kim, Hi Chul; Kim, Gi-Hwan; Shum, David; Cho, Ssang-Goo; Lee, Eun Ju; Kwon, Yong-Jun

    2016-01-01

    Here, we developed a cell defined siRNA microarray (CDSM) for human bone marrow stromal cells (hBMSCs) designed to control the culture of cells inside the spot area without reducing the efficiency of siRNA silencing, “Development of a cell-defined siRNA microarray for analysis of gene functionin human bone marrow stromal cells” (Kim et al., 2016 [1]). First, we confirmed that p65 protein inhibition efficiency was maintained when hBMSCs were culture for 7 days on the siRNA spot, and siRNA spot activity remained in spite of long term storage (10 days and 2 months). Additionally, we confirmed p65 protein inhibition in U2OS cells after 48 h reverse transfection. PMID:27054175

  12. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis.

    PubMed

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-05-24

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus.

  13. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis.

    PubMed

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-01-01

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus. PMID:27217336

  14. Functional definition of BirA suggests a biotin utilization pathway in the zoonotic pathogen Streptococcus suis

    PubMed Central

    Ye, Huiyan; Cai, Mingzhu; Zhang, Huimin; Li, Zhencui; Wen, Ronghui; Feng, Youjun

    2016-01-01

    Biotin protein ligase is universal in three domains of life. The paradigm version of BPL is the Escherichia coli BirA that is also a repressor for the biotin biosynthesis pathway. Streptococcus suis, a leading bacterial agent for swine diseases, seems to be an increasingly-important opportunistic human pathogen. Unlike the scenario in E. coli, S. suis lacks the de novo biotin biosynthesis pathway. In contrast, it retains a bioY, a biotin transporter-encoding gene, indicating an alternative survival strategy for S. suis to scavenge biotin from its inhabiting niche. Here we report functional definition of S. suis birA homologue. The in vivo functions of the birA paralogue with only 23.6% identity to the counterpart of E. coli, was judged by its ability to complement the conditional lethal mutants of E. coli birA. The recombinant BirA protein of S. suis was overexpressed in E. coli, purified to homogeneity and verified with MS. Both cellulose TLC and MALDI-TOFF-MS assays demonstrated that the S. suis BirA protein catalyzed the biotinylation reaction of its acceptor biotin carboxyl carrier protein. EMSA assays confirmed binding of the bioY gene to the S. suis BirA. The data defined the first example of the bifunctional BirA ligase/repressor in Streptococcus. PMID:27217336

  15. Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization

    NASA Astrophysics Data System (ADS)

    Miyamoto, Mayumi; Matsuzaki, Kentaro; Katakura, Masanori; Hara, Toshiko; Tanabe, Yoko; Shido, Osamu

    2015-10-01

    The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

  16. Oral intake of encapsulated dried ginger root powder hardly affects human thermoregulatory function, but appears to facilitate fat utilization.

    PubMed

    Miyamoto, Mayumi; Matsuzaki, Kentaro; Katakura, Masanori; Hara, Toshiko; Tanabe, Yoko; Shido, Osamu

    2015-10-01

    The present study investigated the impact of a single oral ingestion of ginger on thermoregulatory function and fat oxidation in humans. Morning and afternoon oral intake of 1.0 g dried ginger root powder did not alter rectal temperature, skin blood flow, O2 consumption, CO2 production, and thermal sensation and comfort, or induce sweating at an ambient temperature of 28 °C. Ginger ingestion had no effect on threshold temperatures for skin blood flow or thermal sweating. Serum levels of free fatty acids were significantly elevated at 120 min after ginger ingestion in both the morning and afternoon. Morning ginger intake significantly reduced respiratory exchange ratios and elevated fat oxidation by 13.5 % at 120 min after ingestion. This was not the case in the afternoon. These results suggest that the effect of a single oral ginger administration on the peripheral and central thermoregulatory function is miniscule, but does facilitate fat utilization although the timing of the administration may be relevant.

  17. Defining the Interactions of Cellobiohydrolase with Substrate through Structure Function Studies: Cooperative Research and Development Final Report, CRADA Number CRD-10-409

    SciTech Connect

    Beckham, G. T.; Himmel, M. E.

    2013-07-01

    NREL researchers will use their expertise and skilled resources in numerical computational modeling to generate structure-function relationships for improved cellulase variant enzymes to support the development of cellulases with improved performance in biomass conversion.

  18. Highly efficient SO2 absorption/activation and subsequent utilization by polyethylene glycol-functionalized Lewis basic ionic liquids.

    PubMed

    Yang, Zhen-Zhen; He, Liang-Nian; Song, Qing-Wen; Chen, Kai-Hong; Liu, An-Hua; Liu, Xiang-Ming

    2012-12-01

    Up to now, flue-gas desulfurization (FGD) is one of the most effective techniques to control SO(2) emission from the combustion of fossil fuels. The conventional technology for FGD poses serious inherent drawbacks such as formation of byproducts and volatilization of solvents. In this work, polyethylene glycol (PEG)-functionalized Lewis basic ionic liquids (ILs) derived from DABCO were proved to be highly efficient absorbents for FGD due to its specific features such as high thermal stability, negligible vapor pressure, high loading capacity. Notably, PEG(150)MeDABCONTf(2) gave an extremely high SO(2) capacity (4.38 mol mol(-1) IL), even under 0.1 bar SO(2) partial pressure (1.01 mol mol(-1) IL), presumably owing to the strong SO(2)-philic characterization of the PEG chain. Furthermore, the absorbed SO(2) could be easy to release by just bubbling N(2) at room temperature, greatly reducing energy requirement for SO(2) desorption. In addition, SO(2)/CO(2) selectivity (110) of PEG(150)MeDABCONTf(2) is two times larger than the non-functionalized imidazolium IL (45). On the other hand, through activation of SO(2) with the tertiary nitrogen in the cation, Lewis basic ILs such as PEG(150)MeDABCOBr proved to be efficient catalysts for the conversion of SO(2) to some value-added chemicals such as cyclic sulfites without utilization of any organic solvent or additive. Thus, this protocol would pave the way for the development of technological innovation towards efficient and low energy demanded practical process for SO(2) absorption and subsequent transformation.

  19. A methodology for selecting the beam arrangement to reduce the intensity-modulated radiation therapy (IMRT) dose to the SPECT-defined functioning lung

    NASA Astrophysics Data System (ADS)

    McGuire, S. M.; Marks, L. B.; Yin, F. F.; Das, S. K.

    2010-01-01

    Macroaggregated albumin single-photon emission computed tomography (MAA-SPECT) provides a map of the spatial distribution of lung perfusion. Our previous work developed a methodology to use SPECT guidance to reduce the dose to the functional lung in IMRT planning. This study aims to investigate the role of beam arrangement on both low and high doses in the functional lung. In our previous work, nine-beam IMRT plans were generated with and without SPECT guidance and compared for five patients. For the current study, the dose-function histogram (DFH) contribution for each of the nine beams for each patient was calculated. Four beams were chosen based on orientation and DFH contributions to create a SPECT-guided plan that spared the functional lung and maintained target coverage. Four-beam SPECT-guided IMRT plans reduced the F20 and F30 values by (16.5 ± 6.8)% and (6.1 ± 9.2)%, respectively, when compared to nine-beam conventional IMRT plans. Moreover, the SPECT-4F Plan reduces F5 and F13 for all patients by (11.0 ± 8.2)% and (6.1 ± 3.6)%, respectively, compared to the SPECT Plan. Using fewer beams in IMRT planning may reduce the amount of functional lung that receives 5 and 13 Gy, a factor that has recently been associated with radiation pneumonitis.

  20. A methodology for selecting the beam arrangement to reduce the intensity-modulated radiation therapy (IMRT) dose to the SPECT-defined functioning lung.

    PubMed

    McGuire, S M; Marks, L B; Yin, F F; Das, S K

    2010-01-21

    Macroaggregated albumin single-photon emission computed tomography (MAA-SPECT) provides a map of the spatial distribution of lung perfusion. Our previous work developed a methodology to use SPECT guidance to reduce the dose to the functional lung in IMRT planning. This study aims to investigate the role of beam arrangement on both low and high doses in the functional lung. In our previous work, nine-beam IMRT plans were generated with and without SPECT guidance and compared for five patients. For the current study, the dose-function histogram (DFH) contribution for each of the nine beams for each patient was calculated. Four beams were chosen based on orientation and DFH contributions to create a SPECT-guided plan that spared the functional lung and maintained target coverage. Four-beam SPECT-guided IMRT plans reduced the F(20) and F(30) values by (16.5 +/- 6.8)% and (6.1 +/- 9.2)%, respectively, when compared to nine-beam conventional IMRT plans. Moreover, the SPECT-4F Plan reduces F(5) and F(13) for all patients by (11.0 +/- 8.2)% and (6.1 +/- 3.6)%, respectively, compared to the SPECT Plan. Using fewer beams in IMRT planning may reduce the amount of functional lung that receives 5 and 13 Gy, a factor that has recently been associated with radiation pneumonitis. PMID:20019404

  1. Defining the nociceptor transcriptome.

    PubMed

    Thakur, Matthew; Crow, Megan; Richards, Natalie; Davey, Gareth I J; Levine, Emma; Kelleher, Jayne H; Agley, Chibeza C; Denk, Franziska; Harridge, Stephen D R; McMahon, Stephen B

    2014-01-01

    Unbiased "omics" techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for studies of neuronal injury, regeneration and pain. The majority of investigators utilize a dissociated preparation of whole ganglia when studying cellular and molecular function. We demonstrate that the standard methods for producing these preparations gives a 10%-neuronal mixture of cells, with the remainder of cells constituting satellite glia and other non-neuronal cell types. Using a novel application of magnetic purification, we consistently obtain over 95% pure, viable neurons from adult tissue, significantly enriched for small diameter nociceptors expressing the voltage gated ion channel Nav1.8. Using genome-wide RNA-sequencing we compare the currently used (10% neuronal) and pure (95% nociceptor) preparations and find 920 genes enriched. This gives an unprecedented insight into the molecular composition of small nociceptive neurons in the DRG, potentially altering the interpretation of previous studies performed at the tissue level, and indicating a number of novel markers of this widely-studied population of cells. We anticipate that the ease of use, affordability and speed of this technique will see it become widely adopted, delivering a greatly improved capacity to study the roles of nociceptors in health and disease. PMID:25426020

  2. Defining the nociceptor transcriptome

    PubMed Central

    Thakur, Matthew; Crow, Megan; Richards, Natalie; Davey, Gareth I. J.; Levine, Emma; Kelleher, Jayne H.; Agley, Chibeza C.; Denk, Franziska; Harridge, Stephen D. R.; McMahon, Stephen B.

    2014-01-01

    Unbiased “omics” techniques, such as next generation RNA-sequencing, can provide entirely novel insights into biological systems. However, cellular heterogeneity presents a significant barrier to analysis and interpretation of these datasets. The neurons of the dorsal root ganglia (DRG) are an important model for studies of neuronal injury, regeneration and pain. The majority of investigators utilize a dissociated preparation of whole ganglia when studying cellular and molecular function. We demonstrate that the standard methods for producing these preparations gives a 10%-neuronal mixture of cells, with the remainder of cells constituting satellite glia and other non-neuronal cell types. Using a novel application of magnetic purification, we consistently obtain over 95% pure, viable neurons from adult tissue, significantly enriched for small diameter nociceptors expressing the voltage gated ion channel Nav1.8. Using genome-wide RNA-sequencing we compare the currently used (10% neuronal) and pure (95% nociceptor) preparations and find 920 genes enriched. This gives an unprecedented insight into the molecular composition of small nociceptive neurons in the DRG, potentially altering the interpretation of previous studies performed at the tissue level, and indicating a number of novel markers of this widely-studied population of cells. We anticipate that the ease of use, affordability and speed of this technique will see it become widely adopted, delivering a greatly improved capacity to study the roles of nociceptors in health and disease. PMID:25426020

  3. SPO14 separation-of-function mutations define unique roles for phospholipase D in secretion and cellular differentiation in Saccharomyces cerevisiae.

    PubMed Central

    Rudge, S A; Pettitt, T R; Zhou, C; Wakelam, M J; Engebrecht, J A

    2001-01-01

    In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene, catalyzes the hydrolysis of phosphatidylcholine, producing choline and phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis and is required for Golgi function when the normal secretory apparatus is perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14 that support Sec14-independent secretion but not sporulation. Identification of these separation-of-function alleles indicates that the role of PLD in these two physiological processes is distinct. Analyses of the mutants reveal that the corresponding proteins are stable, phosphorylated, catalytically active in vitro, and can localize properly within the cell during meiosis. Surprisingly, the separation-of-function mutations map to the conserved catalytic region of the PLD protein. Choline and phosphatidic acid molecular species profiles during Sec14-independent secretion and meiosis reveal that while strains harboring one of these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent secretion, they fail to do so during sporulation or normal vegetative growth. These results demonstrate that Spo14 PLD catalytic activity and cellular function can be differentially regulated at the level of phosphatidylcholine hydrolysis. PMID:11514437

  4. Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population

    SciTech Connect

    Thomas, Y.; Rogozinski, L.; Irigoyen, O.H.; Friedman, S.M.; Kung, P.C.; Goldstein, G.; Chess, L.

    1981-08-01

    In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

  5. Defining the Metabolic Functions and Roles in Virulence of the rpoN1 and rpoN2 Genes in Ralstonia solanacearum GMI1000

    PubMed Central

    Lundgren, Benjamin R.; Connolly, Morgan P.; Choudhary, Pratibha; Brookins-Little, Tiffany S.; Chatterjee, Snigdha; Raina, Ramesh; Nomura, Christopher T.

    2015-01-01

    The alternative sigma factor RpoN is a unique regulator found among bacteria. It controls numerous processes that range from basic metabolism to more complex functions such as motility and nitrogen fixation. Our current understanding of RpoN function is largely derived from studies on prototypical bacteria such as Escherichia coli. Bacillus subtilis and Pseudomonas putida. Although the extent and necessity of RpoN-dependent functions differ radically between these model organisms, each bacterium depends on a single chromosomal rpoN gene to meet the cellular demands of RpoN regulation. The bacterium Ralstonia solanacearum is often recognized for being the causative agent of wilt disease in crops, including banana, peanut and potato. However, this plant pathogen is also one of the few bacterial species whose genome possesses dual rpoN genes. To determine if the rpoN genes in this bacterium are genetically redundant and interchangeable, we constructed and characterized ΔrpoN1, ΔrpoN2 and ΔrpoN1 ΔrpoN2 mutants of R. solanacearum GMI1000. It was found that growth on a small range of metabolites, including dicarboxylates, ethanol, nitrate, ornithine, proline and xanthine, were dependent on only the rpoN1 gene. Furthermore, the rpoN1 gene was required for wilt disease on tomato whereas rpoN2 had no observable role in virulence or metabolism in R. solanacearum GMI1000. Interestingly, plasmid-based expression of rpoN2 did not fully rescue the metabolic deficiencies of the ΔrpoN1 mutants; full recovery was specific to rpoN1. In comparison, only rpoN2 was able to genetically complement a ΔrpoN E. coli mutant. These results demonstrate that the RpoN1 and RpoN2 proteins are not functionally equivalent or interchangeable in R. solanacearum GMI1000. PMID:26659655

  6. Defining the Metabolic Functions and Roles in Virulence of the rpoN1 and rpoN2 Genes in Ralstonia solanacearum GMI1000.

    PubMed

    Lundgren, Benjamin R; Connolly, Morgan P; Choudhary, Pratibha; Brookins-Little, Tiffany S; Chatterjee, Snigdha; Raina, Ramesh; Nomura, Christopher T

    2015-01-01

    The alternative sigma factor RpoN is a unique regulator found among bacteria. It controls numerous processes that range from basic metabolism to more complex functions such as motility and nitrogen fixation. Our current understanding of RpoN function is largely derived from studies on prototypical bacteria such as Escherichia coli. Bacillus subtilis and Pseudomonas putida. Although the extent and necessity of RpoN-dependent functions differ radically between these model organisms, each bacterium depends on a single chromosomal rpoN gene to meet the cellular demands of RpoN regulation. The bacterium Ralstonia solanacearum is often recognized for being the causative agent of wilt disease in crops, including banana, peanut and potato. However, this plant pathogen is also one of the few bacterial species whose genome possesses dual rpoN genes. To determine if the rpoN genes in this bacterium are genetically redundant and interchangeable, we constructed and characterized ΔrpoN1, ΔrpoN2 and ΔrpoN1 ΔrpoN2 mutants of R. solanacearum GMI1000. It was found that growth on a small range of metabolites, including dicarboxylates, ethanol, nitrate, ornithine, proline and xanthine, were dependent on only the rpoN1 gene. Furthermore, the rpoN1 gene was required for wilt disease on tomato whereas rpoN2 had no observable role in virulence or metabolism in R. solanacearum GMI1000. Interestingly, plasmid-based expression of rpoN2 did not fully rescue the metabolic deficiencies of the ΔrpoN1 mutants; full recovery was specific to rpoN1. In comparison, only rpoN2 was able to genetically complement a ΔrpoN E. coli mutant. These results demonstrate that the RpoN1 and RpoN2 proteins are not functionally equivalent or interchangeable in R. solanacearum GMI1000.

  7. Defining the Metabolic Functions and Roles in Virulence of the rpoN1 and rpoN2 Genes in Ralstonia solanacearum GMI1000.

    PubMed

    Lundgren, Benjamin R; Connolly, Morgan P; Choudhary, Pratibha; Brookins-Little, Tiffany S; Chatterjee, Snigdha; Raina, Ramesh; Nomura, Christopher T

    2015-01-01

    The alternative sigma factor RpoN is a unique regulator found among bacteria. It controls numerous processes that range from basic metabolism to more complex functions such as motility and nitrogen fixation. Our current understanding of RpoN function is largely derived from studies on prototypical bacteria such as Escherichia coli. Bacillus subtilis and Pseudomonas putida. Although the extent and necessity of RpoN-dependent functions differ radically between these model organisms, each bacterium depends on a single chromosomal rpoN gene to meet the cellular demands of RpoN regulation. The bacterium Ralstonia solanacearum is often recognized for being the causative agent of wilt disease in crops, including banana, peanut and potato. However, this plant pathogen is also one of the few bacterial species whose genome possesses dual rpoN genes. To determine if the rpoN genes in this bacterium are genetically redundant and interchangeable, we constructed and characterized ΔrpoN1, ΔrpoN2 and ΔrpoN1 ΔrpoN2 mutants of R. solanacearum GMI1000. It was found that growth on a small range of metabolites, including dicarboxylates, ethanol, nitrate, ornithine, proline and xanthine, were dependent on only the rpoN1 gene. Furthermore, the rpoN1 gene was required for wilt disease on tomato whereas rpoN2 had no observable role in virulence or metabolism in R. solanacearum GMI1000. Interestingly, plasmid-based expression of rpoN2 did not fully rescue the metabolic deficiencies of the ΔrpoN1 mutants; full recovery was specific to rpoN1. In comparison, only rpoN2 was able to genetically complement a ΔrpoN E. coli mutant. These results demonstrate that the RpoN1 and RpoN2 proteins are not functionally equivalent or interchangeable in R. solanacearum GMI1000. PMID:26659655

  8. Upper Limb Evaluation in Duchenne Muscular Dystrophy: Fat-Water Quantification by MRI, Muscle Force and Function Define Endpoints for Clinical Trials

    PubMed Central

    Ricotti, Valeria; Evans, Matthew R. B.; Sinclair, Christopher D. J.; Butler, Jordan W.; Ridout, Deborah A.; Hogrel, Jean-Yves; Emira, Ahmed; Morrow, Jasper M.; Reilly, Mary M.; Hanna, Michael G.; Janiczek, Robert L.; Matthews, Paul M.; Yousry, Tarek A.; Muntoni, Francesco; Thornton, John S.

    2016-01-01

    Objective A number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function. Methods 15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation. Results Overall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001). A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7), accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9) and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8). Conclusions These results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function. PMID

  9. Heme Utilization in Bordetella avium Is Regulated by RhuI, a Heme-Responsive Extracytoplasmic Function Sigma Factor

    PubMed Central

    Kirby, Amy E.; Metzger, Daniel J.; Murphy, Erin R.; Connell, Terry D.

    2001-01-01

    Efficient utilization of heme as an iron (Fe) source by Bordetella avium requires bhuR, an Fe-regulated gene which encodes an outer membrane heme receptor. Upstream of bhuR is a 507-bp open reading frame, hereby designated rhuI (for regulator of heme uptake), which codes for a 19-kDa polypeptide. Whereas the 19-kDa polypeptide had homology to a subfamily of alternative sigma factors known as the extracytoplasmic function (ECF) sigma factors, it was hypothesized that rhuI encoded a potential in-trans regulator of the heme receptor gene in trans. Support for the model was strengthened by the identification of nucleotide sequences common to ECF sigma-dependent promoters in the region immediately upstream of bhuR. Experimental evidence for the regulatory activities of rhuI was first revealed by recombinant experiments in which overproduction of rhuI was correlated with a dramatically increased expression of BhuR. A putative rhuI-dependent bhuR promoter was identified in the 199-bp region located proximal to bhuR. When a transcriptional fusion of the 199-bp region and a promoterless lacZ gene was introduced into Escherichia coli, promoter activity was evident, but only when rhuI was coexpressed in the cell. Sigma competition experiments in E. coli demonstrated that rhuI conferred biological properties on the cell that were consistent with RhuI having sigma factor activity. Heme, hemoglobin, and several other heme-containing proteins were shown to be the extracellular inducers of the rhuI-dependent regulatory system. Fur titration assays indicated that expression of rhuI was probably Fur dependent. PMID:11598070

  10. Defining Early Adolescent Childbearing.

    ERIC Educational Resources Information Center

    Phipps, Maureen G.; Sowers, MaryFran

    2002-01-01

    Determined the age group for defining early adolescent childbearing based on rates of adverse clinical outcomes. Data on infant mortality, very low birth weight, and very pre-term delivery per 1,000 live births for women age 12-23 years in the 1995 U.S. birth cohort indicate that early adolescent childbearing is best defined as giving birth at age…

  11. Orbiter electrical equipment utilization baseline

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The baseline for utilization of Orbiter electrical equipment in both electrical and Environmental Control and Life Support System (ECLSS) thermal analyses is established. It is a composite catalog of Space Shuttle equipment, as defined in the Shuttle Operational Data Book. The major functions and expected usage of each component type are described. Functional descriptions are designed to provide a fundamental understanding of the Orbiter electrical equipment, to insure correlation of equipment usage within nominal analyses, and to aid analysts in the formulation of off-nominal, contingency analyses.

  12. Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.

    PubMed

    Fabina, Nicholas S; Putnam, Hollie M; Franklin, Erik C; Stat, Michael; Gates, Ruth D

    2013-11-01

    Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches.

  13. Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways

    PubMed Central

    Westlake, Timothy J.; Ricci, William A.; Popescu, George V.; Popescu, Sorina C.

    2015-01-01

    A long-term goal in plant research is to understand how plants integrate signals from multiple environmental stressors. The importance of salicylic acid (SA) in plant response to biotic and abiotic stress is known, yet the molecular details of the SA-mediated pathways are insufficiently understood. Our recent work identified the peptidases TOP1 and TOP2 as critical components in plant response to pathogens and programmed cell death (PCD). In this study, we investigated the characteristics of TOPs related to the regulation of their enzymatic activity and function in oxidative stress response. We determined that TOP1 and TOP2 interact with themselves and each other and their ability to associate in dimers is influenced by SA and the thiol-based reductant DTT. Biochemical characterization of TOP1 and TOP2 indicated distinct sensitivities to DTT and similarly robust activity under a range of pH values. Treatments of top mutants with Methyl Viologen (MV) revealed TOP1 and TOP2 as a modulators of the plant tolerance to MV, and that exogenous SA alleviates the toxicity of MV in top background. Finally, we generated a TOP-centered computational model of a plant cell whose simulation outputs replicate experimental findings and predict novel functions of TOP1 and TOP2. Altogether, our work indicates that TOP1 and TOP2 mediate plant responses to oxidative stress through spatially separated pathways and positions proteolysis in a network for plant response to diverse stressors. PMID:26042129

  14. Defining the essential function of FBP/KSRP proteins: Drosophila Psi interacts with the mediator complex to modulate MYC transcription and tissue growth.

    PubMed

    Guo, Linna; Zaysteva, Olga; Nie, Zuqin; Mitchell, Naomi C; Amanda Lee, Jue Er; Ware, Thomas; Parsons, Linda; Luwor, Rodney; Poortinga, Gretchen; Hannan, Ross D; Levens, David L; Quinn, Leonie M

    2016-09-19

    Despite two decades of research, the major function of FBP-family KH domain proteins during animal development remains controversial. The literature is divided between RNA processing and transcriptional functions for these single stranded nucleic acid binding proteins. Using Drosophila, where the three mammalian FBP proteins (FBP1-3) are represented by one ortholog, Psi, we demonstrate the primary developmental role is control of cell and tissue growth. Co-IP-mass spectrometry positioned Psi in an interactome predominantly comprised of RNA Polymerase II (RNA Pol II) transcriptional machinery and we demonstrate Psi is a potent transcriptional activator. The most striking interaction was between Psi and the transcriptional mediator (MED) complex, a known sensor of signaling inputs. Moreover, genetic manipulation of MED activity modified Psi-dependent growth, which suggests Psi interacts with MED to integrate developmental growth signals. Our data suggest the key target of the Psi/MED network in controlling developmentally regulated tissue growth is the transcription factor MYC. As FBP1 has been implicated in controlling expression of the MYC oncogene, we predict interaction between MED and FBP1 might also have implications for cancer initiation and progression.

  15. Defining the essential function of FBP/KSRP proteins: Drosophila Psi interacts with the mediator complex to modulate MYC transcription and tissue growth

    PubMed Central

    Guo, Linna; Zaysteva, Olga; Nie, Zuqin; Mitchell, Naomi C.; Amanda Lee, Jue Er; Ware, Thomas; Parsons, Linda; Luwor, Rodney; Poortinga, Gretchen; Hannan, Ross D.; Levens, David L.; Quinn, Leonie M.

    2016-01-01

    Despite two decades of research, the major function of FBP-family KH domain proteins during animal development remains controversial. The literature is divided between RNA processing and transcriptional functions for these single stranded nucleic acid binding proteins. Using Drosophila, where the three mammalian FBP proteins (FBP1-3) are represented by one ortholog, Psi, we demonstrate the primary developmental role is control of cell and tissue growth. Co-IP-mass spectrometry positioned Psi in an interactome predominantly comprised of RNA Polymerase II (RNA Pol II) transcriptional machinery and we demonstrate Psi is a potent transcriptional activator. The most striking interaction was between Psi and the transcriptional mediator (MED) complex, a known sensor of signaling inputs. Moreover, genetic manipulation of MED activity modified Psi-dependent growth, which suggests Psi interacts with MED to integrate developmental growth signals. Our data suggest the key target of the Psi/MED network in controlling developmentally regulated tissue growth is the transcription factor MYC. As FBP1 has been implicated in controlling expression of the MYC oncogene, we predict interaction between MED and FBP1 might also have implications for cancer initiation and progression. PMID:27207882

  16. Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.

    PubMed

    Fabina, Nicholas S; Putnam, Hollie M; Franklin, Erik C; Stat, Michael; Gates, Ruth D

    2013-11-01

    Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches. PMID:23847174

  17. Cerebral blood flow with [15O]water PET studies using an image-derived input function and MR-defined carotid centerlines

    NASA Astrophysics Data System (ADS)

    Fung, Edward K.; Carson, Richard E.

    2013-03-01

    Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [15O]water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 ± 0.09 at 0-30 s post tracer arrival, 0.45 ± 0.09 at 30-60 s, and 0.46 ± 0.09 at 60-90 s. Gray and white matter CBF values were 61.4 ± 11.0 and 15.6 ± 3.0 mL/min/100 g tissue using sampled blood data. Using IDIF centerlines scaled by the average aRC over each subjects’ injections, gray and white matter CBF values were 61.3 ± 13.5 and 15.5 ± 3.4 mL/min/100 g tissue. Using global

  18. Defining the Functional Potential and Active Community Members of a Sediment Microbial Community in a High-Arctic Hypersaline Subzero Spring

    PubMed Central

    Lay, Chih-Ying; Mykytczuk, Nadia C. S.; Yergeau, Étienne; Lamarche-Gagnon, Guillaume; Greer, Charles W.

    2013-01-01

    The Lost Hammer (LH) Spring is the coldest and saltiest terrestrial spring discovered to date and is characterized by perennial discharges at subzero temperatures (−5°C), hypersalinity (salinity, 24%), and reducing (≈−165 mV), microoxic, and oligotrophic conditions. It is rich in sulfates (10.0%, wt/wt), dissolved H2S/sulfides (up to 25 ppm), ammonia (≈381 μM), and methane (11.1 g day−1). To determine its total functional and genetic potential and to identify its active microbial components, we performed metagenomic analyses of the LH Spring outlet microbial community and pyrosequencing analyses of the cDNA of its 16S rRNA genes. Reads related to Cyanobacteria (19.7%), Bacteroidetes (13.3%), and Proteobacteria (6.6%) represented the dominant phyla identified among the classified sequences. Reconstruction of the enzyme pathways responsible for bacterial nitrification/denitrification/ammonification and sulfate reduction appeared nearly complete in the metagenomic data set. In the cDNA profile of the LH Spring active community, ammonia oxidizers (Thaumarchaeota), denitrifiers (Pseudomonas spp.), sulfate reducers (Desulfobulbus spp.), and other sulfur oxidizers (Thermoprotei) were present, highlighting their involvement in nitrogen and sulfur cycling. Stress response genes for adapting to cold, osmotic stress, and oxidative stress were also abundant in the metagenome. Comparison of the composition of the functional community of the LH Spring to metagenomes from other saline/subzero environments revealed a close association between the LH Spring and another Canadian high-Arctic permafrost environment, particularly in genes related to sulfur metabolism and dormancy. Overall, this study provides insights into the metabolic potential and the active microbial populations that exist in this hypersaline cryoenvironment and contributes to our understanding of microbial ecology in extreme environments. PMID:23563939

  19. A new genetic method for isolating functionally interacting genes: high plo1(+)-dependent mutants and their suppressors define genes in mitotic and septation pathways in fission yeast.

    PubMed Central

    Cullen, C F; May, K M; Hagan, I M; Glover, D M; Ohkura, H

    2000-01-01

    We describe a general genetic method to identify genes encoding proteins that functionally interact with and/or are good candidates for downstream targets of a particular gene product. The screen identifies mutants whose growth depends on high levels of expression of that gene. We apply this to the plo1(+) gene that encodes a fission yeast homologue of the polo-like kinases. plo1(+) regulates both spindle formation and septation. We have isolated 17 high plo1(+)-dependent (pld) mutants that show defects in mitosis or septation. Three mutants show a mitotic arrest phenotype. Among the 14 pld mutants with septation defects, 12 mapped to known loci: cdc7, cdc15, cdc11 spg1, and sid2. One of the pld mutants, cdc7-PD1, was selected for suppressor analysis. As multicopy suppressors, we isolated four known genes involved in septation in fission yeast: spg1(+), sce3(+), cdc8(+), and rho1(+), and two previously uncharacterized genes, mpd1(+) and mpd2(+). mpd1(+) exhibits high homology to phosphatidylinositol 4-phosphate 5-kinase, while mpd2(+) resembles Saccharomyces cerevisiae SMY2; both proteins are involved in the regulation of actin-mediated processes. As chromosomal suppressors of cdc7-PD1, we isolated mutations of cdc16 that resulted in multiseptation without nuclear division. cdc16(+), dma1(+), byr3(+), byr4(+) and a truncated form of the cdc7 gene were isolated by complementation of one of these cdc16 mutations. These results demonstrate that screening for high dose-dependent mutants and their suppressors is an effective approach to identify functionally interacting genes. PMID:10924454

  20. Arabidopsis CBF1 and CBF3 have a different function than CBF2 in cold acclimation and define different gene classes in the CBF regulon

    PubMed Central

    Novillo, Fernando; Medina, Joaquín; Salinas, Julio

    2007-01-01

    The C-repeat-binding factor (CBF)/dehydration-responsive element-binding factor (DREB1) proteins constitute a small family of Arabidopsis transcriptional activators (CBF1/DREB1B, CBF2/DREB1C, and CBF3/DREB1A) that play a prominent role in cold acclimation. A fundamental question about these factors that remains to be answered is whether they are functionally equivalent. Recently, we reported that CBF2 negatively regulates CBF1 and CBF3 expression, and that CBFs are subjected to different temporal regulation during cold acclimation, which suggested this might not be the case. In this study, we have analyzed the expression of CBF genes in different tissues of Arabidopsis, during development and in response to low temperature, and characterized RNA interference (RNAi) and antisense lines that fail to accumulate CBF1 or/and CBF3 mRNAs under cold conditions. We found that CBF1 and CBF3 are regulated in a different way than CBF2. Moreover, in contrast to CBF2, CBF1 and CBF3 are not involved in regulating other CBF genes and positively regulate cold acclimation by activating the same subset of CBF-target genes. All these results demonstrate that CBF1 and CBF3 have different functions than CBF2. We also found that the CBF regulon is composed of at least two different kind of genes, one of them requiring the simultaneous expression of both CBF1 and CBF3 to be properly induced. This indicates that CBF1 and CBF3 have a concerted additive effect to induce the whole CBF regulon and the complete development of cold acclimation. PMID:18093929

  1. Conflict in the parameters defining life and death in Missouri statutes.

    PubMed

    Schoen, W L

    1990-01-01

    Over the last twenty years, state legislatures have enacted statutes incorporating medically and legally established criteria to be utilized in the determination of death. Similarly consistent criteria for determining the onset of life have yet to be established. As a result, unacceptably conflicting statutory language defining life and the state's interest in that life exists. This conflict can be resolved by a functional approach that consistently applies criteria used to define the end of life to the beginning of life.

  2. Eliciting and Combining Decision Criteria Using a Limited Palette of Utility Functions and Uncertainty Distributions: Illustrated by Application to Pest Risk Analysis.

    PubMed

    Holt, Johnson; Leach, Adrian W; Schrader, Gritta; Petter, Françoise; MacLeod, Alan; van der Gaag, Dirk Jan; Baker, Richard H A; Mumford, John D

    2014-01-01

    Utility functions in the form of tables or matrices have often been used to combine discretely rated decision-making criteria. Matrix elements are usually specified individually, so no one rule or principle can be easily stated for the utility function as a whole. A series of five matrices are presented that aggregate criteria two at a time using simple rules that express a varying degree of constraint of the lower rating over the higher. A further nine possible matrices were obtained by using a different rule either side of the main axis of the matrix to describe situations where the criteria have a differential influence on the outcome. Uncertainties in the criteria are represented by three alternative frequency distributions from which the assessors select the most appropriate. The output of the utility function is a distribution of rating frequencies that is dependent on the distributions of the input criteria. In pest risk analysis (PRA), seven of these utility functions were required to mimic the logic by which assessors for the European and Mediterranean Plant Protection Organization arrive at an overall rating of pest risk. The framework enables the development of PRAs that are consistent and easy to understand, criticize, compare, and change. When tested in workshops, PRA practitioners thought that the approach accorded with both the logic and the level of resolution that they used in the risk assessments.

  3. Eliciting and Combining Decision Criteria Using a Limited Palette of Utility Functions and Uncertainty Distributions: Illustrated by Application to Pest Risk Analysis.

    PubMed

    Holt, Johnson; Leach, Adrian W; Schrader, Gritta; Petter, Françoise; MacLeod, Alan; van der Gaag, Dirk Jan; Baker, Richard H A; Mumford, John D

    2014-01-01

    Utility functions in the form of tables or matrices have often been used to combine discretely rated decision-making criteria. Matrix elements are usually specified individually, so no one rule or principle can be easily stated for the utility function as a whole. A series of five matrices are presented that aggregate criteria two at a time using simple rules that express a varying degree of constraint of the lower rating over the higher. A further nine possible matrices were obtained by using a different rule either side of the main axis of the matrix to describe situations where the criteria have a differential influence on the outcome. Uncertainties in the criteria are represented by three alternative frequency distributions from which the assessors select the most appropriate. The output of the utility function is a distribution of rating frequencies that is dependent on the distributions of the input criteria. In pest risk analysis (PRA), seven of these utility functions were required to mimic the logic by which assessors for the European and Mediterranean Plant Protection Organization arrive at an overall rating of pest risk. The framework enables the development of PRAs that are consistent and easy to understand, criticize, compare, and change. When tested in workshops, PRA practitioners thought that the approach accorded with both the logic and the level of resolution that they used in the risk assessments. PMID:23834916

  4. Tracking Behavior Assessment Methodology and Support Strategies: A National Survey of How Schools Utilize Functional Behavioral Assessments and Behavior Intervention Plans

    ERIC Educational Resources Information Center

    Couvillon, Michael A.; Bullock, Lyndal M.; Gable, Robert A.

    2009-01-01

    Although functional behavioral assessments (FBAs) and behavior intervention plans (BIPs) have been utilized since the 1960s, their use has steadily increased since the passing of IDEA 1997 which mandated their use in specified circumstances. References to FBAs and BIPs in No Child Left Behind Act of 2001, the 2004 re-authorization of IDEA, and in…

  5. Defining the states of consciousness.

    PubMed

    Tassi, P; Muzet, A

    2001-03-01

    Consciousness remains an elusive concept due to the difficulty to define what has been regarded for many years as a subjective experience, therefore irrelevant for scientific study. Recent development in this field of research has allowed to provide some new insight to a possible way to define consciousness. Going through the extensive literature in this domain, several perspectives are proposed to define this concept. (1) Consciousness and Attention may not reflect the same process. (2) Consciousness during wake and sleep may not involve the same mechanisms. (3) Besides physiological states of consciousness, human beings can experience modified states of consciousness either by self-training (transcendental meditation, hypnosis, etc.) or by drug intake (hallucinogens, anaesthetics, etc.). Altogether, we address the question of a more precise terminology, given the theoretical weight words can convey. To this respect, we propose different definitions for concepts like consciousness, vigilance, arousal and alertness as candidates to separate functional entities.

  6. Defining Overweight and Obesity

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  7. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

    PubMed

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A; Highland, Heather M; Locke, Adam E; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J; Teslovich, Tanya M; Rayner, N William; Robertson, Neil R; Beer, Nicola L; Rundle, Jana K; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P; Gabriel, Stacey; Gjesing, Anette P; Groves, Christopher J; Hollensted, Mette; Huyghe, Jeroen R; Jackson, Anne U; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S; Stringham, Heather M; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I; Blangero, John; Cox, Nancy J; Duggirala, Ravindranath; Hanis, Craig L; Seielstad, Mark; Wilson, James G; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L; Doney, Alex S F; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D; Morris, Andrew D; Palmer, Colin N A; Collins, Francis S; Mohlke, Karen L; Bergman, Richard N; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C; Morris, Andrew P; Altshuler, David; Meigs, James B; Boehnke, Michael; McCarthy, Mark I; Lindgren, Cecilia M; Gloyn, Anna L

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  8. Niemann-Pick C1 (NPC1)/NPC1-like1 chimeras define sequences critical for NPC1's function as a flovirus entry receptor.

    PubMed

    Krishnan, Anuja; Miller, Emily Happy; Herbert, Andrew S; Ng, Melinda; Ndungo, Esther; Whelan, Sean P; Dye, John M; Chandran, Kartik

    2012-10-25

    We recently demonstrated that Niemann-Pick C1 (NPC1), a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1), an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C) of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1’s domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid N–terminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of N–terminal domain C sequences in NPC1’s function as a filovirus receptor.

  9. Niemann-Pick C1 (NPC1)/NPC1-like1 chimeras define sequences critical for NPC1's function as a flovirus entry receptor.

    PubMed

    Krishnan, Anuja; Miller, Emily Happy; Herbert, Andrew S; Ng, Melinda; Ndungo, Esther; Whelan, Sean P; Dye, John M; Chandran, Kartik

    2012-11-01

    We recently demonstrated that Niemann-Pick C1 (NPC1), a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1), an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C) of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1’s domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid N–terminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of N–terminal domain C sequences in NPC1’s function as a filovirus receptor. PMID:23202491

  10. Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells.

    PubMed

    Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja; Hong, Jung Joo; Iyer, Smita S; Gumber, Sanjeev; Ibegbu, Chris C; Villinger, Francois; Amara, Rama Rao

    2016-09-01

    Chronic HIV infection is associated with accumulation of germinal center (GC) T follicular helper (Tfh) cells in the lymphoid tissue. The GC Tfh cells can be heterogeneous based on the expression of chemokine receptors associated with T helper lineages, such as CXCR3 (Th1), CCR4 (Th2), and CCR6 (Th17). However, the heterogeneous nature of GC Tfh cells in the lymphoid tissue and its association with viral persistence and Ab production during chronic SIV/HIV infection are not known. To address this, we characterized the expression of CXCR3, CCR4, and CCR6 on GC Tfh cells in lymph nodes following SIVmac251 infection in rhesus macaques. In SIV-naive rhesus macaques, only a small fraction of GC Tfh cells expressed CXCR3, CCR4, and CCR6. However, during chronic SIV infection, the majority of GC Tfh cells expressed CXCR3, whereas the proportion of CCR4(+) cells did not change, and CCR6(+) cells decreased. CXCR3(+), but not CXCR3(-), GC Tfh cells produced IFN-γ (Th1 cytokine) and IL-21 (Tfh cytokine), whereas both subsets expressed CD40L following stimulation. Immunohistochemistry analysis demonstrated an accumulation of CD4(+)IFN-γ(+) T cells within the hyperplastic follicles during chronic SIV infection. CXCR3(+) GC Tfh cells also expressed higher levels of ICOS, CCR5, and α4β7 and contained more copies of SIV DNA compared with CXCR3(-) GC Tfh cells. However, CXCR3(+) and CXCR3(-) GC Tfh cells delivered help to B cells in vitro for production of IgG. These data demonstrate that chronic SIV infection promotes expansion of Th1-biased GC Tfh cells, which are phenotypically and functionally distinct from conventional GC Tfh cells and contribute to hypergammaglobulinemia and viral reservoirs. PMID:27481845

  11. Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

    PubMed Central

    Mahajan, Anubha; Sim, Xueling; Ng, Hui Jin; Manning, Alisa; Rivas, Manuel A.; Highland, Heather M.; Locke, Adam E.; Grarup, Niels; Im, Hae Kyung; Cingolani, Pablo; Flannick, Jason; Fontanillas, Pierre; Fuchsberger, Christian; Gaulton, Kyle J.; Teslovich, Tanya M.; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Bork-Jensen, Jette; Ladenvall, Claes; Blancher, Christine; Buck, David; Buck, Gemma; Burtt, Noël P.; Gabriel, Stacey; Gjesing, Anette P.; Groves, Christopher J.; Hollensted, Mette; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S.; Stringham, Heather M.; Syvänen, Ann-Christine; Trakalo, Joseph; Abecasis, Goncalo; Bell, Graeme I.; Blangero, John; Cox, Nancy J.; Duggirala, Ravindranath; Hanis, Craig L.; Seielstad, Mark; Wilson, James G.; Christensen, Cramer; Brandslund, Ivan; Rauramaa, Rainer; Surdulescu, Gabriela L.; Doney, Alex S. F.; Lannfelt, Lars; Linneberg, Allan; Isomaa, Bo; Tuomi, Tiinamaija; Jørgensen, Marit E.; Jørgensen, Torben; Kuusisto, Johanna; Uusitupa, Matti; Salomaa, Veikko; Spector, Timothy D.; Morris, Andrew D.; Palmer, Colin N. A.; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Ingelsson, Erik; Lind, Lars; Tuomilehto, Jaakko; Hansen, Torben; Watanabe, Richard M.; Prokopenko, Inga; Dupuis, Josee; Karpe, Fredrik; Groop, Leif; Laakso, Markku; Pedersen, Oluf; Florez, Jose C.; Morris, Andrew P.; Altshuler, David; Meigs, James B.; Boehnke, Michael; McCarthy, Mark I.; Lindgren, Cecilia M.; Gloyn, Anna L.

    2015-01-01

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights. PMID:25625282

  12. CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function

    PubMed Central

    Mizuta, Shumpei; Minami, Tomoya; Fujita, Haruka; Kaminaga, Chihiro; Matsui, Keiji; Ishino, Ruri; Fujita, Azusa; Oda, Kasumi; Kawai, Asami; Hasegawa, Natsumi; Urahama, Norinaga; Roeder, Robert G.; Ito, Mitsuhiro

    2015-01-01

    The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1-targeted gene transcription and erythroid differentiation. An N-terminal fragment of MED1, MED1(1–602), which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation, and introduction of MED1(1–602) into Med1−/− mouse embryonic fibroblasts (MEFs) partially rescued GATA1-mediated transcription. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1–602)-interacting coactivator CCAR1, CoCoA, and MED1(681–715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription from the γ-globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA, and MED1(1–602) formed a complex in vitro, and GATA1, CCAR1, CoCoA, and MED1 were recruited to the γ-globin promoter in K562 cells during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events. PMID:24245781

  13. Dopamine Reward Prediction Error Responses Reflect Marginal Utility

    PubMed Central

    Stauffer, William R.; Lak, Armin; Schultz, Wolfram

    2014-01-01

    Summary Background Optimal choices require an accurate neuronal representation of economic value. In economics, utility functions are mathematical representations of subjective value that can be constructed from choices under risk. Utility usually exhibits a nonlinear relationship to physical reward value that corresponds to risk attitudes and reflects the increasing or decreasing marginal utility obtained with each additional unit of reward. Accordingly, neuronal reward responses coding utility should robustly reflect this nonlinearity. Results In two monkeys, we measured utility as a function of physical reward value from meaningful choices under risk (that adhered to first- and second-order stochastic dominance). The resulting nonlinear utility functions predicted the certainty equivalents for new gambles, indicating that the functions’ shapes were meaningful. The monkeys were risk seeking (convex utility function) for low reward and risk avoiding (concave utility function) with higher amounts. Critically, the dopamine prediction error responses at the time of reward itself reflected the nonlinear utility functions measured at the time of choices. In particular, the reward response magnitude depended on the first derivative of the utility function and thus reflected the marginal utility. Furthermore, dopamine responses recorded outside of the task reflected the marginal utility of unpredicted reward. Accordingly, these responses were sufficient to train reinforcement learning models to predict the behaviorally defined expected utility of gambles. Conclusions These data suggest a neuronal manifestation of marginal utility in dopamine neurons and indicate a common neuronal basis for fundamental explanatory constructs in animal learning theory (prediction error) and economic decision theory (marginal utility). PMID:25283778

  14. Defining departmental mission.

    PubMed

    Hartman, M D; Barrow, J A; Sawyer, W R

    1990-02-01

    Mission statements have long been recognized by corporate America as a way to define an enterprise. The necessary business orientation of the health care industry requires that hospitals and hospital departments define their scope of services and reason for existence. The accelerating reprofessionalization affecting departments of pharmacy requires the same. "Improving the quality of patient care" can no longer represent a euphemism for simply reacting to external factors or acting on a whim without clear meaningful intent. Professional departments and hospitals must demonstrate a sense of direction and purpose and be able to justify costs to a budget-conscious management and skeptical public. Mission statements are not substitutes for a clearly defined sense of professional mission. However, well-constructed mission statements contribute to clarity of departmental and professional purpose and effective achievement of goals. PMID:10128549

  15. Defining Risk Drinking

    PubMed Central

    Dawson, Deborah A.

    2011-01-01

    Many efforts to prevent alcohol-related harm are aimed at reducing risk drinking. This article outlines the many conceptual and methodological challenges to defining risk drinking. It summarizes recent evidence regarding associations of various aspects of alcohol consumption with chronic and acute alcohol-related harms, including mortality, morbidity, injury, and alcohol use disorders, and summarizes the study designs most appropriate to defining risk thresholds for these types of harm. In addition, it presents an international overview of low-risk drinking guidelines from more than 20 countries, illustrating the wide range of interpretations of the scientific evidence related to risk drinking. This article also explores the impact of drink size on defining risk drinking and describes variation in what is considered to be a standard drink across populations. Actual and standard drink sizes differ in the United States, and this discrepancy affects definitions of risk drinking and prevention efforts. PMID:22330212

  16. Defining the Human Microbiome

    PubMed Central

    Ursell, Luke K; Metcalf, Jessica L; Parfrey, Laura Wegener; Knight, Rob

    2012-01-01

    Rapidly developing sequencing methods and analytical techniques are enhancing our ability to understand the human microbiome, and, indeed, how we define the microbiome and its constituents. In this review we highlight recent research that expands our ability to understand the human microbiome on different spatial and temporal scales, including daily timeseries datasets spanning months. Furthermore, we discuss emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes and the possibility of enterotypes. Additional advances in sequencing technology and in our understanding of the microbiome will provide exciting prospects for exploiting the microbiota for personalized medicine. PMID:22861806

  17. Impact of nutrition on immune function and the inflammatory response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The review utilizes data on three micronutrients (vitamin A, zinc and iron), anthropometrically defined undernutrition (stunting, wasting and underweight) and obesity to evaluate the effect on immune function, recovery of immune function in response to nutritional interventions, related health outco...

  18. Defining Faculty Work.

    ERIC Educational Resources Information Center

    Gray, Peter J.; Diamond, Robert M.

    1994-01-01

    A process of planned change is proposed for redefining college faculty work. Legitimate faculty work is defined in broad terms, and information sources and methods for collecting information to support redefinition are identified. The final step in the redefinition process is the development of new mission statements for the institution and its…

  19. Defining Child Abuse.

    ERIC Educational Resources Information Center

    Giovannoni, Jeanne M.; Becerra, Rosina M.

    In seeking to clarify the meaning of the terms "child abuse" and "child neglect" it has been assumed that, like other forms of social deviance, they are socially defined phenomena. Interviews were conducted with those professionals (lawyers, pediatricians, police officers, and social workers) who daily handle the problems of abuse and neglect for…

  20. Defined by Limitations

    ERIC Educational Resources Information Center

    Arriola, Sonya; Murphy, Katy

    2010-01-01

    Undocumented students are a population defined by limitations. Their lack of legal residency and any supporting paperwork (e.g., Social Security number, government issued identification) renders them essentially invisible to the American and state governments. They cannot legally work. In many states, they cannot legally drive. After the age of…

  1. Defining Effective Teaching

    ERIC Educational Resources Information Center

    Layne, L.

    2012-01-01

    The author looks at the meaning of specific terminology commonly used in student surveys: "effective teaching." The research seeks to determine if there is a difference in how "effective teaching" is defined by those taking student surveys and those interpreting the results. To investigate this difference, a sample group of professors and students…

  2. Defining and Assessing Quality.

    ERIC Educational Resources Information Center

    Fincher, Cameron, Ed.

    The seven papers in this monograph focus on defining and assessing quality. The paper are: (1) "Reflections on Design Ideals" (E. Grady Bogue), which addresses some "governing ideals" of collegiate quality; (2) "Between a Rock and a Hard Place: Investment and Quality in Higher Education" (Sven Groennings), which sees the competitive quality of…

  3. On Defining Mass

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement…

  4. Defining Equality in Education

    ERIC Educational Resources Information Center

    Benson, Ronald E.

    1977-01-01

    Defines equality of education in three areas: 1) by the degree of integration of school systems; 2) by a comparison of material resources and assets in education; and 3) by the effects of schooling as measured by the mean scores of groups on standardized tests. Available from: College of Education, 107 Quadrangle, Iowa State University, Ames, Iowa…

  5. Modeling of a 3DTV service in the software-defined networking architecture

    NASA Astrophysics Data System (ADS)

    Wilczewski, Grzegorz

    2014-11-01

    In this article a newly developed concept towards modeling of a multimedia service offering stereoscopic motion imagery is presented. Proposed model is based on the approach of utilization of Software-defined Networking or Software Defined Networks architecture (SDN). The definition of 3D television service spanning SDN concept is identified, exposing basic characteristic of a 3DTV service in a modern networking organization layout. Furthermore, exemplary functionalities of the proposed 3DTV model are depicted. It is indicated that modeling of a 3DTV service in the Software-defined Networking architecture leads to multiplicity of improvements, especially towards flexibility of a service supporting heterogeneity of end user devices.

  6. Human chimera-type galectin-3: defining the critical tail length for high-affinity glycoprotein/cell surface binding and functional competition with galectin-1 in neuroblastoma cell growth regulation.

    PubMed

    Kopitz, Jürgen; Vértesy, Sabine; André, Sabine; Fiedler, Sabine; Schnölzer, Martina; Gabius, Hans-Joachim

    2014-09-01

    Many human proteins have a modular design with receptor and structural domains. Using adhesion/growth-regulatory galectin-3 as model, we describe an interdisciplinary strategy to define the functional significance of its tail established by nine non-triple helical collagen-like repeats (I-IX) and the N-terminal peptide. Genetic engineering with sophisticated mass spectrometric product analysis provided the tools for biotesting, i.e. eight protein variants with different degrees of tail truncation. Evidently,various aspects of galectin-3 activity (cis binding and cell bridging) are affected by tail shortening in a different manner. Thus, this combined approach reveals an unsuspected complexity of structure-function relationship, encouraging further application beyond this chimera-type galectin.

  7. On the User-Level Satisfactions with User-Level Utility Functions: A Case Study with Scheduling in TDMA Wireless Networks

    NASA Astrophysics Data System (ADS)

    Kim, Sungyeon; Lee, Jang-Won

    In most cases in wireless networks, a user has a two-way communication that consists of two sessions: uplink and downlink sessions, and its overall satisfaction to the communication depends on the quality of service of both sessions. However, in most previous approaches in wireless resource allocation, the satisfactions of a user for its uplink and downlink sessions are modeled separately and treated independently, which fails to accurately model user's overall satisfaction to its communication. Hence, in this paper we model user's overall satisfaction to its communication considering both its uplink and downlink sessions. To this end, we propose a novel concept for a utility function to model user's overall satisfaction to its communication, which is called a user-level utility function, considering user's satisfaction to uplink and downlink sessions jointly. To show the appropriateness of our approach, we apply our user-level utility functions to scheduling problems in TDMA wireless networks and show the performance improvement of our approach over the traditional approach that does not treat uplink and downlink sessions of a user jointly.

  8. The Clinical Utility of the Behavior Rating Inventory of Executive Function (BRIEF) in the Diagnosis of ADHD

    ERIC Educational Resources Information Center

    McCandless, Stephen; O'Laughlin, Liz

    2007-01-01

    Objective: Current theories hypothesize that deficits in executive functioning (EF) are responsible for the symptoms of ADHD and that specific patterns of EF deficits may be associated with different subtypes of ADHD. The present study evaluates the validity and clinical usefulness of the Behavior Rating Inventory of Executive Function, a behavior…

  9. Strain energy release rate as a function of temperature and preloading history utilizing the edge delamination fatique test method

    NASA Technical Reports Server (NTRS)

    Zimmerman, Richard S.; Adams, Donald F.

    1989-01-01

    Static laminate and tension-tension fatigue tests of IM7/8551-7 composite materials was performed. The Edge Delamination Test (EDT) was utilized to evaluate the temperature and preloading history effect on the critical strain energy release rate. Static and fatigue testing was performed at room temperature and 180 F (82 C). Three preloading schemes were used to precondition fatigue test specimens prior to performing the normal tension-tension fatigue EDT testing. Computer software was written to perform all fatigue testing while monitoring the dynamic modulus to detect the onset of delamination and record the test information for later retrieval and reduction.

  10. Higher comorbidity, poor functional status and higher health care utilization in veterans with prevalent total knee arthroplasty or total hip arthroplasty

    PubMed Central

    Sloan, Jeffrey

    2010-01-01

    The objective of this study was to compare comorbidity, functional ability, and health care utilization in veterans with total knee arthroplasty (TKA) or total hip arthroplasty (THA) versus matched control populations. A cohort of veterans using Veterans Affairs (VA) healthcare system reported limitations in six activities of daily living (ADLs; bathing, dressing, eating, walking, transferring, and using the toilet), demographics, and physician-diagnosed comorbidity. VA databases provided healthcare utilization and International Classification of Diseases-9/Common procedure terminology codes for TKA/THA. Patients were classified as: (1) primary TKA; (2) primary THA; (3) combination group (≤1 procedure); and (4) control veteran population (no THA/TKA). Multivariable regression analyses compared the risk or counts of ADL limitation and in-/out-patient visits. After multivariable adjustment, TKA, THA or combination groups had significantly higher prevalence of the following compared to veteran controls: arthritis, diabetes, or heart disease (p<0.0001 each), severe (≥3) ADL limitation (33%, 42%, 42% vs. 24%; p<0.0001), and annual hospitalization rate (24%, 19%, 26% vs. 16%, p<0.0001). Annual outpatient surgery visits were more (2.5, 2.3, 2.3 vs. 2, p=0.01) and risk of any mental health outpatient visit was lower (12%, 11%, 12% vs. 18%, p=0.0039). All ADLs, except eating, were significantly more limited in arthroplasty groups (p= 0.0009). Severe ADL limitation was more prevalent in veterans with arthroplasty than in two age-matched US cohorts: 13.4 times in ≥65 years; and 1.2-, 1.6-, and 4-fold in ≥85, 75–84, and 65–74 years. Poorer function and higher comorbidity and utilization in veterans with TKA/THA suggest that this group is appropriate for interventions targeted at improving function and decreasing utilization. PMID:19517157

  11. Higher comorbidity, poor functional status and higher health care utilization in veterans with prevalent total knee arthroplasty or total hip arthroplasty.

    PubMed

    Singh, Jasvinder A; Sloan, Jeffrey

    2009-09-01

    The objective of this study was to compare comorbidity, functional ability, and health care utilization in veterans with total knee arthroplasty (TKA) or total hip arthroplasty (THA) versus matched control populations. A cohort of veterans using Veterans Affairs (VA) healthcare system reported limitations in six activities of daily living (ADLs; bathing, dressing, eating, walking, transferring, and using the toilet), demographics, and physician-diagnosed comorbidity. VA databases provided healthcare utilization and International Classification of Diseases-9/Common procedure terminology codes for TKA/THA. Patients were classified as: (1) primary TKA; (2) primary THA; (3) combination group (>or=1 procedure); and (4) control veteran population (no THA/TKA). Multivariable regression analyses compared the risk or counts of ADL limitation and in-/out-patient visits. After multivariable adjustment, TKA, THA or combination groups had significantly higher prevalence of the following compared to veteran controls: arthritis, diabetes, or heart disease (p < 0.0001 each), severe (>or=3) ADL limitation (33%, 42%, 42% vs. 24%; p < 0.0001), and annual hospitalization rate (24%, 19%, 26% vs. 16%, p < 0.0001). Annual outpatient surgery visits were more (2.5, 2.3, 2.3 vs. 2, p = 0.01) and risk of any mental health outpatient visit was lower (12%, 11%, 12% vs. 18%, p = 0.0039). All ADLs, except eating, were significantly more limited in arthroplasty groups (p or=65 years; and 1.2-, 1.6-, and 4-fold in >or=85, 75-84, and 65-74 years. Poorer function and higher comorbidity and utilization in veterans with TKA/THA suggest that this group is appropriate for interventions targeted at improving function and decreasing utilization.

  12. The Potential Utility of Eye Movements in the Detection and Characterization of Everyday Functional Difficulties in Mild Cognitive Impairment.

    PubMed

    Seligman, Sarah C; Giovannetti, Tania

    2015-06-01

    Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.

  13. Personality disorders and physical health: A longitudinal examination of physical functioning, healthcare utilization, and health-related behaviors in middle-aged adults

    PubMed Central

    Powers, Abigail D.; Oltmanns, Thomas F.

    2011-01-01

    Personality disorders (PDs) have significant, long-term effects in many areas, including physical health outcomes such as increased risk for chronic disease and mortality. Although research has documented this detrimental impact in relation to long-term physical health, no one has explored the more immediate influence of disordered personality on aspects of physical functioning, such as pain level, or health-related behaviors, such as medication use. The present study examined the unique effects of PD features on physical functioning, medical resource utilization, and prescription medication use to determine potential risk associated with PDs. We studied an epidemiologically-based sample (N=608) of Saint Louis residents (ages 55–64) over two time points (6 months apart). We found that disordered personality was significantly predictive of worse physical functioning, role limitations, fatigue, and pain at both time points, even when current health problems, the presence of depression, and health behaviors (i.e., smoking, drinking, exercise) were controlled. PD features were also predictive of increased healthcare utilization and medication use at follow-up. These results suggest that the presence of disordered personality may be an important risk factor for worse functioning, regardless of actual health status. PMID:22867504

  14. Utilization of near-source video and ground motion in the assessment of seismic source functions from mining explosions

    SciTech Connect

    Anderson, D.P.; Stump, B.W.

    1994-09-01

    Identification of seismic events detected under a Comprehensive Test Ban Treaty requires a clear physical understanding of the different types of seismic sources including mining explosions, rock bursts, mine collapse and small, shallow earthquakes. Constraint of the operative physical processes in the source region and linkage to the generation of seismic waveforms with particular emphasis on regional seismograms is needed. In order to properly address the multi-dimensional aspect of data sets designed to constrain these sources, we are investigating a number of modern visualization tools that have only recently become available with new, high-speed graphical computers that can utilize relatively large data sets. The results of this study will provide a basis for identifying important processes in the source region that contribute to regional seismograms.

  15. Utilization of near-source video and ground motion in the assessment of seismic source functions from mining explosions

    SciTech Connect

    Stump, B.W.; Anderson, D.P.

    1995-04-01

    Constraint of the operative physical processes in the source region of mining explosions and the linkage to the generation of seismic waveforms provides the opportunity for controlling ground motion. Development of these physical models can also be used in conjunction with the ground motion data as diagnostics of blasting efficiency. In order to properly address the multi-dimensional aspect of data sets designed to constrain these sources, we are investigating a number of modem visualization tools that have only recently become available with new, high-speed graphical computers that can utilize relatively large data sets. The data sets that are combined in the study of mining explosion sources include near-source ground motion acceleration and velocity records, velocity of detonation measurements in each explosive hole, high speed film, video and shot design information.

  16. Structural and Functional Insights into (S)-Ureidoglycolate Dehydrogenase, a Metabolic Branch Point Enzyme in Nitrogen Utilization

    PubMed Central

    Kim, Myung-Il; Shin, Inchul; Cho, Suhee; Lee, Jeehyun; Rhee, Sangkee

    2012-01-01

    Nitrogen metabolism is one of essential processes in living organisms. The catabolic pathways of nitrogenous compounds play a pivotal role in the storage and recovery of nitrogen. In Escherichia coli, two different, interconnecting metabolic routes drive nitrogen utilization through purine degradation metabolites. The enzyme (S)-ureidoglycolate dehydrogenase (AllD), which is a member of l-sulfolactate dehydrogenase-like family, converts (S)-ureidoglycolate, a key intermediate in the purine degradation pathway, to oxalurate in an NAD(P)-dependent manner. Therefore, AllD is a metabolic branch-point enzyme for nitrogen metabolism in E. coli. Here, we report crystal structures of AllD in its apo form, in a binary complex with NADH cofactor, and in a ternary complex with NADH and glyoxylate, a possible spontaneous degradation product of oxalurate. Structural analyses revealed that NADH in an extended conformation is bound to an NADH-binding fold with three distinct domains that differ from those of the canonical NADH-binding fold. We also characterized ligand-induced structural changes, as well as the binding mode of glyoxylate, in the active site near the NADH nicotinamide ring. Based on structural and kinetic analyses, we concluded that AllD selectively utilizes NAD+ as a cofactor, and further propose that His116 acts as a general catalytic base and that a hydride transfer is possible on the B-face of the nicotinamide ring of the cofactor. Other residues conserved in the active sites of this novel l-sulfolactate dehydrogenase-like family also play essential roles in catalysis. PMID:23284870

  17. Defining of the BDX930 Assembly Language

    NASA Technical Reports Server (NTRS)

    Boyer, R. S.; Moore, J. S.

    1983-01-01

    A definition of the BDX930 assembly language is presented. Various definition problems and suggested solutions are included. A class of defined recognizers based on boolean valued nowrecursive functions is employed in preprocessing.

  18. Utilization of high resolution computed tomography to visualize the three dimensional structure and function of plant vasculature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High resolution x-ray computed tomography (HRCT) is a non-destructive diagnostic imaging technique with sub-micron resolution capability that is now being used to evaluate the structure and function of plant xylem network in three dimensions (3D). HRCT imaging is based on the same principles as medi...

  19. TAPERED DEFINING SLOT

    DOEpatents

    Pressey, F.W.

    1959-09-01

    An improvement is reported in the shape and formation of the slot or opening in the collimating slot member which forms part of an ion source of the type wherein a vapor of the material to be ionized is bombarded by electrons in a magnetic field to strike an arc-producing ionization. The defining slot is formed so as to have a substantial taper away from the cathode, causing the electron bombardment from the cathode to be dispersed over a greater area reducing its temperature and at the same time bringing the principal concentration of heat from the electron bombardment nearer the anode side of the slot, thus reducing deterioration and prolonging the life of the slot member during operation.

  20. Defining the mobilome.

    PubMed

    Siefert, Janet L

    2009-01-01

    This chapter defines the agents that provide for the movement of genetic material which fuels the adaptive potential of life on our planet. The chapter has been structured to be broadly comprehensive, arbitrarily categorizing the mobilome into four classes: (1) transposons, (2) plasmids, (3) bacteriophage, and (4) self-splicing molecular parasites.Our increasing understanding of the mobilome is as dynamic as the mobilome itself. With continuing discovery, it is clear that nature has not confined these genomic agents of change to neat categories, but rather the classification categories overlap and intertwine. Massive sequencing efforts and their published analyses are continuing to refine our understanding of the extent of the mobilome. This chapter provides a framework to describe our current understanding of the mobilome and a foundation on which appreciation of its impact on genome evolution can be understood.

  1. Utilization of information from gene networks towards a better understanding of functional similarities between complex traits: a dairy cattle model.

    PubMed

    Frąszczak, Magdalena; Suchocki, Tomasz; Szyda, Joanna

    2016-02-01

    Our study focused on quantifying functional similarities between complex traits recorded in dairy cattle: milk yield, fat yield, protein yield, somatic cell score and stature. Similarities were calculated based on gene sets forming gene networks and on gene ontology term sets underlying genes estimated as significant for the analysed traits. Gene networks were obtained by the Bisogenet and Gene Set Linkage Analysis (GSLA) software. The highest similarity was observed between milk yield and fat yield. A very low degree of similarity was attributed to protein yield and stature when using gene sets as a similarity criterion, as well as to protein yield and fat yield when using sets of gene ontology terms. Pearson correlation coefficients between gene effect estimates, representing additive polygenic similarities, were highest for protein yield and milk yield, and the lowest in case of protein yield and somatic cell score. Using the 50 K Illumina SNP chip from the national genomic selection data set only the most significant gene-trait associations can be retrieved, while enhancing it by the functional information contained in interaction data stored in public data bases and by metabolic pathways information facilitates a better characterization of the functional background of the traits and furthermore - trait comparison. The most interesting result of our study was that the functional similarity observed between protein yield and milk-/fat yields contradicted moderate genetic correlations estimated earlier for the same population based on a multivariate mixed model. The discrepancy indicates that an infinitesimal model assumed in that study reflects an averaged correlation due to polygenes, but fails to reveal the functional background underlying the traits, which is due to the cumulative composition of many genes involved in metabolic pathways, which appears to differ between protein-fat yield and protein-milk yield pairs.

  2. Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation.

    PubMed

    Welberry Smith, Matthew P; Zougman, Alexandre; Cairns, David A; Wilson, Michelle; Wind, Tobias; Wood, Steven L; Thompson, Douglas; Messenger, Michael P; Mooney, Andrew; Selby, Peter J; Lewington, Andrew J P; Banks, Rosamonde E

    2013-12-01

    Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67-0.85) for ACY-1, 0.9 (0.84-0.95) for cystatin C, and 0.93 (0.88-0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor-brain-dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation.

  3. Reliability, validity, and clinical utility of the Executive Function Performance Test: a measure of executive function in a sample of people with stroke.

    PubMed

    Baum, Carolyn M; Connor, Lisa Tabor; Morrison, Tracy; Hahn, Michelle; Dromerick, Alexander W; Edwards, Dorothy F

    2008-01-01

    This study examined the reliability and validity of the Executive Function Performance Test (EFPT). The EFPT assesses executive function deficits in the performance of real-world tasks. It uses a structured cueing and scoring system to assess higher-level cognitive functions, specifically initiation, organization, sequencing safety and judgment, and task completion. Seventy-three participants with mild to moderate stroke and 22 age- and education-matched controls completed the 4 EFPT tasks (cooking, using the telephone, managing medications, and paying bills). Significant differences were found between participants with mild and moderate stroke and healthy control participants. The EFPT can help occupational therapists determine the level of support needed by people with cognitive impairments to perform complex instrumental tasks. Objective information derived from this assessment is an essential part of the process of determining whether the person can live independently and helping families understand how to support the performance of their family members at home. PMID:18712007

  4. [Measures to prevent patient identification errors in blood collection/physiological function testing utilizing a laboratory information system].

    PubMed

    Shimazu, Chisato; Hoshino, Satoshi; Furukawa, Taiji

    2013-08-01

    We constructed an integrated personal identification workflow chart using both bar code reading and an all in-one laboratory information system. The information system not only handles test data but also the information needed for patient guidance in the laboratory department. The reception terminals at the entrance, displays for patient guidance and patient identification tools at blood-sampling booths are all controlled by the information system. The number of patient identification errors was greatly reduced by the system. However, identification errors have not been abolished in the ultrasound department. After re-evaluation of the patient identification process in this department, we recognized that the major reason for the errors came from excessive identification workflow. Ordinarily, an ultrasound test requires patient identification 3 times, because 3 different systems are required during the entire test process, i.e. ultrasound modality system, laboratory information system and a system for producing reports. We are trying to connect the 3 different systems to develop a one-time identification workflow, but it is not a simple task and has not been completed yet. Utilization of the laboratory information system is effective, but is not yet perfect for patient identification. The most fundamental procedure for patient identification is to ask a person's name even today. Everyday checks in the ordinary workflow and everyone's participation in safety-management activity are important for the prevention of patient identification errors.

  5. [Measures to prevent patient identification errors in blood collection/physiological function testing utilizing a laboratory information system].

    PubMed

    Shimazu, Chisato; Hoshino, Satoshi; Furukawa, Taiji

    2013-08-01

    We constructed an integrated personal identification workflow chart using both bar code reading and an all in-one laboratory information system. The information system not only handles test data but also the information needed for patient guidance in the laboratory department. The reception terminals at the entrance, displays for patient guidance and patient identification tools at blood-sampling booths are all controlled by the information system. The number of patient identification errors was greatly reduced by the system. However, identification errors have not been abolished in the ultrasound department. After re-evaluation of the patient identification process in this department, we recognized that the major reason for the errors came from excessive identification workflow. Ordinarily, an ultrasound test requires patient identification 3 times, because 3 different systems are required during the entire test process, i.e. ultrasound modality system, laboratory information system and a system for producing reports. We are trying to connect the 3 different systems to develop a one-time identification workflow, but it is not a simple task and has not been completed yet. Utilization of the laboratory information system is effective, but is not yet perfect for patient identification. The most fundamental procedure for patient identification is to ask a person's name even today. Everyday checks in the ordinary workflow and everyone's participation in safety-management activity are important for the prevention of patient identification errors. PMID:24218775

  6. Defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  7. Use of DNA-stable isotope probing and functional gene probes to investigate the diversity of methyl chloride-utilizing bacteria in soil.

    PubMed

    Borodina, Elena; Cox, Michael J; McDonald, Ian R; Murrell, J Colin

    2005-09-01

    Enrichment and isolation of methyl chloride-utilizing bacteria from various terrestrial environments, including woodland and forest soils, resulted in the identification of seven methyl chloride-utilizing strains belonging to the genus Hyphomicrobium, an Aminobacter strain TW23 and strain WG1, which grouped closely with the genus Mesorhizobium. Methyl chloride enrichment cultures were dominated by Hyphomicrobium species, indicating that these bacteria were most suited to growth under the enrichment and isolation conditions used. However, the application of culture-independent techniques such as DNA-stable isotope probing and the use of a functional gene probe targeting cmuA, which encodes the methyltransferase catalysing the first step in bacterial methyl chloride metabolism, indicated a greater diversity of methyl chloride-utilizing bacteria in the terrestrial environment, compared with the diversity of soil isolates obtained via the enrichment and isolation procedure. It also revealed the presence of as yet uncultured and potentially novel methyl chloride-degrading bacteria in soil. PMID:16104855

  8. Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data

    PubMed Central

    Valli, Isabel; Marquand, Andre F.; Mechelli, Andrea; Raffin, Marie; Allen, Paul; Seal, Marc L.; McGuire, Philip

    2016-01-01

    The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p < 0.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (p < 0.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis. PMID:27092086

  9. Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing

    NASA Astrophysics Data System (ADS)

    Hampson, Robert E.; Gerhardt, Greg A.; Marmarelis, Vasilis; Song, Dong; Opris, Ioan; Santos, Lucas; Berger, Theodore W.; Deadwyler, Sam A.

    2012-10-01

    Objective. Maintenance of cognitive control is a major concern for many human disease conditions; therefore, a major goal of human neuroprosthetics is to facilitate and/or recover the cognitive function when such circumstances impair appropriate decision making. Approach. Minicolumnar activity from the prefrontal cortex (PFC) was recorded from nonhuman primates trained to perform a delayed match to sample (DMS), via custom-designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in the PFC layer 2/3 and layer 5. Such recordings were analyzed via a previously demonstrated nonlinear multi-input-multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multicolumnar firing patterns during DMS performance. Main results. The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance. This allowed the substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection. Such stimulation improved normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following the pharmacological disruption of decision making in the same task. Significance. These findings provide the first successful application of neuroprosthesis in the primate brain designed specifically to restore or repair the disrupted cognitive function.

  10. Condensed phase QM/MM simulations utilizing the exchange core functions to describe exchange repulsions at the QM boundary region

    NASA Astrophysics Data System (ADS)

    Umino, Satoru; Takahashi, Hideaki; Morita, Akihiro

    2016-08-01

    In a recent work, we developed a method [H. Takahashi et al., J. Chem. Phys. 143, 084104 (2015)] referred to as exchange-core function (ECF) approach, to compute exchange repulsion Eex between solute and solvent in the framework of the quantum mechanical (QM)/molecular mechanical (MM) method. The ECF, represented with a Slater function, plays an essential role in determining Eex on the basis of the overlap model. In the work of Takahashi et al. [J. Chem. Phys. 143, 084104 (2015)], it was demonstrated that our approach is successful in computing the hydrogen bond energies of minimal QM/MM systems including a cationic QM solute. We provide in this paper the extension of the ECF approach to the free energy calculation in condensed phase QM/MM systems by combining the ECF and the QM/MM-ER approach [H. Takahashi et al., J. Chem. Phys. 121, 3989 (2004)]. By virtue of the theory of solutions in energy representation, the free energy contribution δμex from the exchange repulsion was naturally formulated. We found that the ECF approach in combination with QM/MM-ER gives a substantial improvement on the calculation of the hydration free energy of a hydronium ion. This can be attributed to the fact that the ECF reasonably realizes the contraction of the electron density of the cation due to the deficit of an electron.

  11. Identifying Individuals at High Risk of Psychosis: Predictive Utility of Support Vector Machine using Structural and Functional MRI Data.

    PubMed

    Valli, Isabel; Marquand, Andre F; Mechelli, Andrea; Raffin, Marie; Allen, Paul; Seal, Marc L; McGuire, Philip

    2016-01-01

    The identification of individuals at high risk of developing psychosis is entirely based on clinical assessment, associated with limited predictive potential. There is, therefore, increasing interest in the development of biological markers that could be used in clinical practice for this purpose. We studied 25 individuals with an at-risk mental state for psychosis and 25 healthy controls using structural MRI, and functional MRI in conjunction with a verbal memory task. Data were analyzed using a standard univariate analysis, and with support vector machine (SVM), a multivariate pattern recognition technique that enables statistical inferences to be made at the level of the individual, yielding results with high translational potential. The application of SVM to structural MRI data permitted the identification of individuals at high risk of psychosis with a sensitivity of 68% and a specificity of 76%, resulting in an accuracy of 72% (p < 0.001). Univariate volumetric between-group differences did not reach statistical significance. By contrast, the univariate fMRI analysis identified between-group differences (p < 0.05 corrected), while the application of SVM to the same data did not. Since SVM is well suited at identifying the pattern of abnormality that distinguishes two groups, whereas univariate methods are more likely to identify regions that individually are most different between two groups, our results suggest the presence of focal functional abnormalities in the context of a diffuse pattern of structural abnormalities in individuals at high clinical risk of psychosis. PMID:27092086

  12. Condensed phase QM/MM simulations utilizing the exchange core functions to describe exchange repulsions at the QM boundary region.

    PubMed

    Umino, Satoru; Takahashi, Hideaki; Morita, Akihiro

    2016-08-28

    In a recent work, we developed a method [H. Takahashi et al., J. Chem. Phys. 143, 084104 (2015)] referred to as exchange-core function (ECF) approach, to compute exchange repulsion Eex between solute and solvent in the framework of the quantum mechanical (QM)/molecular mechanical (MM) method. The ECF, represented with a Slater function, plays an essential role in determining Eex on the basis of the overlap model. In the work of Takahashi et al. [J. Chem. Phys. 143, 084104 (2015)], it was demonstrated that our approach is successful in computing the hydrogen bond energies of minimal QM/MM systems including a cationic QM solute. We provide in this paper the extension of the ECF approach to the free energy calculation in condensed phase QM/MM systems by combining the ECF and the QM/MM-ER approach [H. Takahashi et al., J. Chem. Phys. 121, 3989 (2004)]. By virtue of the theory of solutions in energy representation, the free energy contribution δμex from the exchange repulsion was naturally formulated. We found that the ECF approach in combination with QM/MM-ER gives a substantial improvement on the calculation of the hydration free energy of a hydronium ion. This can be attributed to the fact that the ECF reasonably realizes the contraction of the electron density of the cation due to the deficit of an electron. PMID:27586904

  13. New functionally dioecious bush tomato from northwestern Australia, Solanum ossicruentum, may utilize “trample burr” dispersal

    PubMed Central

    Martine, Christopher T.; Cantley, Jason T.; Frawley, Emma S.; Butler, Alice R.; Jordon-Thaden, Ingrid E.

    2016-01-01

    Abstract A new Australian species of functionally dioecious bush tomato of Solanum subgenus Leptostemonum is described. Solanum ossicruentum Martine & J.Cantley, sp. nov., is thought to be allied with members of the problematic “Dioicum Complex” lineage, but differs in its short silvery indumentum, long calyx lobes, larger stature, and an unusual fruit morphology that may represent “trample burr” seed dispersal. The species occurs in a range extending from the eastern Kimberley in Western Australia to far northwestern Northern Territory and has been recognized for decades as a variant of Solanum dioicum W.Fitzg. Specimens of this species were previously referred to by D.E. Symon and others as Solanum dioicum ‘Tanami.’ Ex situ crossing studies and SEM images of inaperturate pollen grains produced in morphologically hermaphrodite flowers indicate that this taxon is functionally dioecious. The scientific name was chosen with the help of 150 seventh grade life science students from Pennsylvania, USA. PMID:27489475

  14. Facilitation and Restoration of Cognitive Function in Primate Prefrontal Cortex by a Neuroprosthesis that Utilizes Minicolumn-Specific Neural Firing

    PubMed Central

    Hampson, Robert E.; Gerhardt, Greg A.; Marmarelis, Vasilis; Song, Dong; Opris, Ioan; Santos, Lucas; Berger, Theodore W.; Deadwyler, Sam A.

    2012-01-01

    Problem addressed Maintenance of cognitive control is a major concern for many human disease condition, therefore a major goal of human neuroprosthetics is to facilitate and/or recover cognitive function when such circumstances impair appropriate decision making. Methodology Nonhuman primates trained to perform a delayed match to sample (DMS) were employed to record mini-columnar activity in the prefrontal cortex (PFC) via custom designed conformal multielectrode arrays that provided inter-laminar recordings from neurons in PFC layer 2/3 and layer 5. Such recordings were analyzed via a previously demonstrated nonlinear multi-input multi-output (MIMO) neuroprosthesis in rodents, which extracted and characterized multi-columnar firing patterns during DMS performance. Results The MIMO model verified that the conformal recorded individual PFC minicolumns responded to entrained target selections in patterns critical for successful DMS performance. This allowed substitution of task-related layer 5 neuron firing patterns with electrical stimulation in the same recording regions during columnar transmission from layer 2/3 at the time of target selection. Such stimulation facilitated normal task performance, but more importantly, recovered performance when applied as a neuroprosthesis following pharmacological disruption of decision making in the same task. Significance and potential impact These findings provide the first successful application of a neuroprosthesis in primate brain designed specifically to restore or repair disrupted cognitive function. PMID:22976769

  15. Solution-phase parallel synthesis of a pharmacophore library of HUN-7293 analogues: a general chemical mutagenesis approach to defining structure-function properties of naturally occurring cyclic (depsi)peptides.

    PubMed

    Chen, Yan; Bilban, Melitta; Foster, Carolyn A; Boger, Dale L

    2002-05-15

    HUN-7293 (1), a naturally occurring cyclic heptadepsipeptide, is a potent inhibitor of cell adhesion molecule expression (VCAM-1, ICAM-1, E-selectin), the overexpression of which is characteristic of chronic inflammatory diseases. Representative of a general approach to defining structure-function relationships of such cyclic (depsi)peptides, the parallel synthesis and evaluation of a complete library of key HUN-7293 analogues are detailed enlisting solution-phase techniques and simple acid-base liquid-liquid extractions for isolation and purification of intermediates and final products. Significant to the design of the studies and unique to solution-phase techniques, the library was assembled superimposing a divergent synthetic strategy onto a convergent total synthesis. An alanine scan and N-methyl deletion of each residue of the cyclic heptadepsipeptide identified key sites responsible for or contributing to the biological properties. The simultaneous preparation of a complete set of individual residue analogues further simplifying the structure allowed an assessment of each structural feature of 1, providing a detailed account of the structure-function relationships in a single study. Within this pharmacophore library prepared by systematic chemical mutagenesis of the natural product structure, simplified analogues possessing comparable potency and, in some instances, improved selectivity were identified. One potent member of this library proved to be an additional natural product in its own right, which we have come to refer to as HUN-7293B (8), being isolated from the microbial strain F/94-499709.

  16. Assessing the utility of phase-space-localized basis functions: Exploiting direct product structure and a new basis function selection procedure

    NASA Astrophysics Data System (ADS)

    Brown, James; Carrington, Tucker

    2016-06-01

    In this paper we show that it is possible to use an iterative eigensolver in conjunction with Halverson and Poirier's symmetrized Gaussian (SG) basis [T. Halverson and B. Poirier, J. Chem. Phys. 137, 224101 (2012)] to compute accurate vibrational energy levels of molecules with as many as five atoms. This is done, without storing and manipulating large matrices, by solving a regular eigenvalue problem that makes it possible to exploit direct-product structure. These ideas are combined with a new procedure for selecting which basis functions to use. The SG basis we work with is orders of magnitude smaller than the basis made by using a classical energy criterion. We find significant convergence errors in previous calculations with SG bases. For sum-of-product Hamiltonians, SG bases large enough to compute accurate levels are orders of magnitude larger than even simple pruned bases composed of products of harmonic oscillator functions.

  17. Assessing the utility of phase-space-localized basis functions: Exploiting direct product structure and a new basis function selection procedure.

    PubMed

    Brown, James; Carrington, Tucker

    2016-06-28

    In this paper we show that it is possible to use an iterative eigensolver in conjunction with Halverson and Poirier's symmetrized Gaussian (SG) basis [T. Halverson and B. Poirier, J. Chem. Phys. 137, 224101 (2012)] to compute accurate vibrational energy levels of molecules with as many as five atoms. This is done, without storing and manipulating large matrices, by solving a regular eigenvalue problem that makes it possible to exploit direct-product structure. These ideas are combined with a new procedure for selecting which basis functions to use. The SG basis we work with is orders of magnitude smaller than the basis made by using a classical energy criterion. We find significant convergence errors in previous calculations with SG bases. For sum-of-product Hamiltonians, SG bases large enough to compute accurate levels are orders of magnitude larger than even simple pruned bases composed of products of harmonic oscillator functions.

  18. The Utility of Two Shape Matching Error Functions in the Evaluation and Verification of SAC-HTET model Soil Moisture Variables

    NASA Astrophysics Data System (ADS)

    KIM, J.; Smith, M. B.; Koren, V.

    2013-12-01

    The National Oceanic and Atmospheric Administration's (NOAA) - National Weather Service (NWS) has modified the Sacramento Soil Moisture Accounting (SAC-SMA) model to include an advanced treatment of evapotranspiration (SAC-HTET). In this study, we run the SAC-HTET within the Hydrology Laboratory Research Distributed Hydrologic Model (HL-RDHM) to simulate soil moisture grids over the Oklahoma Mesonet domain in real time. The main purpose of this study is to use novel shape-matching error functions to compare simulated soil moisture products with observed soil moisture. We compare the computed soil moisture products at the 4km grid scale with in-situ observations of soil moisture using both traditional measures and two different shape matching or similarity functions: Hausdorff (HAUS) and Earth Mover's Distance (EMD). Soil moisture variables are closely related to soil characteristics which vary greatly in space and depth. HAUS and EMD have the potential to consider these heterogeneities. The HAUS function allows for the incorporation of various factors such as location and depth due to its intrinsically multi-dimensional nature. The EMD function requires the mapping of the set of soil moisture variables into a two dimensional matrix in order to avoid its computational overburden. In this study, we examine the utility of these novel shape matching functions to evaluate the SAC-HTET model.

  19. Defining an emerging disease.

    PubMed

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future. PMID:26470448

  20. Defining an emerging disease.

    PubMed

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future.

  1. Analysis of the metabolic utilization of carbon sources and potential functional diversity of the bacterial community in lab-scale horizontal subsurface-flow constructed wetlands.

    PubMed

    Deng, Huanhuan; Ge, Liyun; Xu, Tan; Zhang, Minghua; Wang, Xuedong; Zhang, Yalei; Peng, Hong

    2011-01-01

    Microorganisms are an integral part of the biogeochemical processes in wetlands. To improve the performance of constructed wetlands, it is very important to know the metabolic properties and functional diversity of the microbial communities. The purpose of this study is to analyze the metabolic properties and functional diversity of the microbial community in a horizontal subsurface-flow constructed wetland (CW) in a laboratory study through the sole-carbon-source utilization profiles using Biolog-ECO microplates. The technique has advantages over traditional cell culture techniques, such as molecular-level techniques-RNA amplification, which are time-consuming, expensive, and only applicable to the small number of species that may be cultured. This CW was designed to treat rural eutrophic water in China, using the plant L. This study showed that the metabolic activities of upper front substrate microorganisms (UF) were greater than those of the lower back substrate microorganisms (LB) in the CW. Integrated areas under average well color development (AWCD) curves of substrate microorganisms in the UF were 131.9, 4.8, and 99.3% higher than in the lower front part (LF), the upper back part (UB), and the LB part of the CW, respectively. Principal components analysis showed significant differences in both community structure and metabolic utilization of carbon sources between substrate microorganisms from different sampling sites. Carbon source utilization of polymers, carbohydrates, carboxylic acids, and amino acids was higher in UF than in LF, but that of amines and phenolic compounds was very similar in UF and LF. The richness, evenness, and diversity of upper substrate microbial communities were significantly higher than those of lower substrate. The LF substrate microbial communities had lower evenness than the other sampling plots, and the lowest richness of substrate microbial community was found in the LB part of the CW.

  2. Estimation of a Q-ratio function for regulated electric utilities: a test of the Stigler-Peltzman hypothesis of regulatory behavior

    SciTech Connect

    Goodfriend, S.J.

    1985-01-01

    The dissertation develops a static model of regulatory equilibria incorporating the Stigler-Peltzman theory of regulatory behavior. The model is used to test empirically the relationship between profitability of the regulated electric utility as measured by the q-ratio, and parameters of the firm's cost and demand functions and the regulator's welfare function. Sample data for 1976, 1977, and 1978 are developed for observations taken from the 100 investor-owned electric utilities followed by Salomon Brothers. Two dependent variables serve as empirical proxies for the theoretical q-ratio. These measures are an empirical q-ratio and the market-to-book ratio of equity. A basic empirical model is selected and tested by ordinary least squares and bounded influence regression. General findings are that the significance of the estimated model is highly sensitive to choice of dependent variable. Only market to book ratio regressions are statistically significant. Among market to book ratio regression, model significance is sensitive to sample year. The 1976 sample produces the most significant model. Regression results, when statistically significant, support the Stigler-Peltzman hypothesis.

  3. Defining senescence and death.

    PubMed

    Thomas, Howard; Ougham, Helen J; Wagstaff, Carol; Stead, Anthony D

    2003-04-01

    This article evaluates features of leaf and flower senescence that are shared with, or are different from, those of other terminal events in plant development. Alterations of plastid structure and function in senescence are often reversible and it is argued that such changes represent a process of transdifferentiation or metaplasia rather than deterioration. It may be that the irreversible senescence of many flowers and some leaves represents the loss of ancestral plasticity during evolution. Reversibility serves to distinguish senescence fundamentally from programmed cell death (PCD), as does the fact that viability is essential for the initiation and progress of cell senescence. Senescence (particularly its timing and location) requires new gene transcription, but the syndrome is also subject to significant post- transcriptional and post-translational regulation. The reversibility of senescence must relate to the plastic, facultative nature of underlying molecular controls. Senescence appears to be cell-autonomous, though definitive evidence is required to substantiate this. The vacuole plays at least three key roles in the development of senescing cells: it defends the cell against biotic and abiotic damage, thus preserving viability, it accumulates metabolites with other functions, such as animal attractants, and it terminates senescence by becoming autolytic and facilitating true cell death. The mechanisms of PCD in plants bear a certain relation to those of apoptosis, and some processes, such as nucleic acid degradation, are superficially similar to aspects of the senescence syndrome. It is concluded that, in terms of physiological components and their controls, senescence and PCD are at best only distantly related.

  4. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    SciTech Connect

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  5. Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery.

    PubMed

    Kahle, Juliette J; Souroullas, George P; Yu, Peng; Zohren, Fabian; Lee, Yoontae; Shaw, Chad A; Zoghbi, Huda Y; Goodell, Margaret A

    2013-03-01

    Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein-protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.

  6. Behavior and space utilization of two common fishes within Caribbean mangroves: implications for the protective function of mangrove habitats

    NASA Astrophysics Data System (ADS)

    MacDonald, J. A.; Shahrestani, S.; Weis, J. S.

    2009-09-01

    Behaviors, activity budgets, and spatial locations of reef-associated schoolmaster snapper ( Lutjanus apodus) and non-reef-associated checkered puffer ( Sphoeroides testudineus) were cataloged in mangrove forests in Caribbean Honduras to see how and where they spent their time and whether this changed as they grew. For schoolmasters, swimming was the most common behavior, while checkered puffers spent the majority of their time resting. Both remained completely within (as opposed to outside) the mangrove roots and in the lower half of the water column most of the time. However, as the size of the fish increased there was a clear decrease in the time spent both within the root system and closer to the substrate; the larger fish spent more time higher up in the water column and outside the root system. This was observed in both the schoolmaster and the puffer; the schoolmaster subsequently moves to reefs while the puffer does not. Coupled with limited feeding, the results suggest a primarily protective function for mangroves.

  7. TEMPO-functionalized zinc phthalocyanine: synthesis, magnetic properties, and its utility for electrochemical sensing of ascorbic acid.

    PubMed

    Korkut, Sibel Eken; Akyüz, Duygu; Özdoğan, Kemal; Yerli, Yusuf; Koca, Atıf; Şener, M Kasım

    2016-02-21

    Zinc(ii) phthalocyanine (TEMPO-ZnPc), peripherally functionalized with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals is synthesized and its magneto structural and electrochemical behaviors are investigated. TEMPO-ZnPc shows multi-electron ring based reduction reactions and a TEMPO based oxidation reaction. Spectroelectrochemical measurements support these peak assignments. TEMPO-ZnPc is tested as a homogeneous and heterogeneous ascorbic acid (AA) sensor. Disappearance of TEMPO-ZnPc based reduction processes and the observation of new waves at around 0 and 1.20 V with respect to increasing AA concentration indicate the interaction of TEMPO-ZnPc with AA and usability of the complex as an electrochemical AA sensor. For practical usage as heterogeneous electrocatalysts for AA sensing, a glassy carbon electrode (GCE) is coated with TEMPO-ZnPc (GCE/TEMPO-ZnPc) and this modified electrode is tested as a heterogeneous AA sensor. The redox peak of GCE/TEMPO-ZnPc at 0.81 V decreases the peak current while a new wave is observed at 0.65 V during the titration of the electrolyte with AA. GCE/TEMPO-ZnPc sense AA with 1.75 × 10(-6) mol dm(-3) LOD with a sensitivity of 1.89 × 10(3) A cm mol(-1).

  8. Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

    PubMed

    Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

    2012-07-18

    With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture. PMID:22730900

  9. Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

    PubMed

    Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

    2012-07-18

    With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture.

  10. Orbital flight simulation utility software unit specifications

    NASA Technical Reports Server (NTRS)

    Wilson, S. W.

    1986-01-01

    The HP PASCAL source code contained in pages 6 through 104 was developed for the Mission Planning and Analysis Division (MPAD) and takes the place of detailed flow charts defining the specifications for a Utility Software Unit designed to support orbital flight simulators such as MANHANDLE and GREAS (General Research and Engineering Analysis Simulator). Besides providing basic input/output, mathematical, vector, matrix, quaternion, and statistical routines for such simulators, one of the primary functions of the Utility Software Unit is to isolate all system-dependent code in one well-defined compartment, thereby facilitating transportation of the simulations from one computer to another. Directives to the PASCAL compilers of the HP-9000 Series 200 PASCAL 3.0 operating system and the HP-9000 Series 500 HP-UX 5.0 operations systems are also provided.

  11. Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation.

    PubMed Central

    Bierer, B E; Peterson, A; Barbosa, J; Seed, B; Burakoff, S J

    1988-01-01

    To define the role of the CD2-lymphocyte function-associated antigen 3 (LFA-3) interaction in T-cell activation, we have expressed a cDNA encoding the human CD2 molecule in a murine antigen-specific T-cell hybridoma. Expression of the CD2 molecule greatly enhances T-cell responsiveness to antigen; this enhancement is inhibited by anti-CD2 and anti-LFA-3 monoclonal antibodies (mAbs). CD2+ hybridomas produce interleukin 2 in response to combinations of anti-CD2 mAbs 9.6 and 9-1 and, in the presence of mAb 9-1, to sheep erythrocytes or to the LFA-3 antigen. Furthermore, hybridomas expressing a mutant CD2 molecule that has lost mAb 9.6 binding do not exhibit the enhanced response to antigen or the ability to respond to LFA-3 plus mAb 9-1, but these hybridomas retain the ability to respond to combinations of anti-CD2 mAbs. The role of the CD2-LFA-3 interaction in T-cell activation and the potential for other physiologic ligands for CD2 are discussed. PMID:2448792

  12. A Space Station Freedom utilization roadmap

    NASA Astrophysics Data System (ADS)

    Kurzhals, Peter R.

    1992-08-01

    Results of an AIAA assessment of Space Station Freedom (SSF) utilization are summarized. The assessment involved 45 representatives nominated by 20 AIAA technical committees to address four key SSF utilization areas (microgravity, life sciences, attached payloads, and small missions) and to lay out a top-level 30-yr roadmap for SSF ultilization. SSF capabilities and support needs for these mission roadmaps are also defined. Specific resultant mission categories and functions are outlined for the four SSF time periods (1995-2000, 2000-2005, 2005-2015, and 2015-2025) addressed by the assessment. Candidate payloads are used to illustrate related SSF utilization benefits and to characterize SSF capabilities required for each of the time periods.

  13. Complete nucleotide sequence of the circular megaplasmid pHCG3 of Oligotropha carboxidovorans: function in the chemolithoautotrophic utilization of CO, H(2) and CO(2).

    PubMed

    Fuhrmann, Sven; Ferner, Marion; Jeffke, Thomas; Henne, Anke; Gottschalk, Gerhard; Meyer, Ortwin

    2003-12-11

    Oligotropha carboxidovorans harbors the low-copy-number, circular, 133,058-bp DNA megaplasmid pHCG3, which is essential in the chemolithoautotrophic utilization of CO (carboxidotrophy), H(2) (hydrogenotrophy) and CO(2) under aerobic conditions. The complete nucleotide sequence of pHCG3 revealed 125 open reading frames. Of these, 95 were identified as putative structural genes. The plasmid carries the four gene clusters cox (14.54 kb, 12 genes), cbb (13.33 kb, 13 genes), hox (23.35 kb, 19 genes plus one ORF) and tra/trb (25.01 kb, 22 genes plus 2 ORFs), which assemble the functions required for the utilization of CO, CO(2) or H(2), and the conjugal transfer of the plasmid, respectively. The gene clusters cox, cbb and hox form a 51.2-kb chemolithoautotrophy module. The tra/trb cluster on the plasmid pHCG3 of O. carboxidovorans has a similar architecture as the Ti-plasmid of Agrobacterium tumefaciens. The tra/trb cluster is separated from the chemolithoautotrophy module by two regions (25.2 and 29.6 kb) with miscellaneous or mostly unknown functions. These regions carry a number of single genes coding for replication and stabilization of pHCG3 as well as the components of a putative system of global regulation of plasmid replication in O. carboxidovorans. An oriV encodes the replication proteins RepABC. Sequence comparisons of pHCG3-encoded genes suggest that major genetic exchange between O. carboxidovorans and the proteobacteria has occurred. PMID:14644498

  14. Investigation of the component processes involved in verbal declarative memory function in bipolar disorder: utility of the Hopkins Verbal Learning Test-Revised.

    PubMed

    Van Rheenen, Tamsyn E; Rossell, Susan L

    2014-08-01

    Evidence suggests that standard learning and recall indexes are sensitive markers of verbal declarative memory ability in bipolar disorder (BD), but no study has examined performance across the full range of component process measures on the Hopkins Verbal Learning Test (HVLT-R) in a BD cohort. As the HVLT-R is part of a widely used battery of cognitive functioning backed by the U.S. Federal Drug Administration as the accepted battery for use in pro-cognitive trials assessing cognitive-enhancing drugs in the related disorder schizophrenia, estimating the utility of its measures in BD is important. Forty-nine BD patients and 51 healthy controls completed the HVLT-R, which was scored for 13 variables of interest, across 4 indices: recall and learning, recognition, strategic organization, and errors. BD patients had greater difficulty in learning the HVLT-R word list compared to controls. They also demonstrated impairment in delayed recall/recognition. There were no differences between the groups in terms of their slope of learning, retrieval index, retention percentage, semantic or serial clustering, errors, or level of retrieval. This pattern was consistent across symptomatic and euthymic patients. The HVLT-R has some utility in characterizing the component processes involved in memory function in BD, such that memory impairments appear to be attributable to deficient encoding processes during the acquisition phase of learning. In the case of planning pro-cognitive clinical trials, the encoding deficits in BD observed here may be sensitive enough to potentially respond to medications designed to enhance the verbal memory performance.

  15. Defining ovarian reserve to better understand ovarian aging

    PubMed Central

    2011-01-01

    Though a widely utilized term and clinical concept, ovarian reserve (OR) has been only inadequately defined. Based on Medline and PubMed searches we here define OR in its various components, review genetic control of OR, with special emphasis on the FMR1 gene, and discuss whether diminished OR (DOR) is treatable. What is generally referred to as OR reflects only a small portion of total OR (TOR), a pool of growing (recruited) follicles (GFs) at different stages of maturation. Functional OR (FOR) depends on size of the follicle pool at menarche and the follicle recruitment rate. Both vary between individuals and, at least partially, are under genetic control. The FMR1 gene plays a role in defining FOR at all ages. Infertility treatments have in the past almost exclusively only centered on the last two weeks of folliculogenesis, the gonadotropin-sensitive phase. Expansions of treatments into earlier stages of maturation will offer opportunity to significantly improve ovarian stimulation protocols, especially in women with DOR. Dehydroepiandrosterone (DHEA) may represent a first such intervention. Data generated in DHEA-supplemented women, indeed, suggest a new ovarian aging concept, based on aging of ovarian environments and not, as currently is believed, aging oocytes. PMID:21299886

  16. Relation of myocardial oxygen consumption and function to high energy phosphate utilization during graded hypoxia and reoxygenation in sheep in vivo.

    PubMed Central

    Portman, M A; Standaert, T A; Ning, X H

    1995-01-01

    This study investigates the relation between myocardial oxygen consumption (MVO2), function, and high energy phosphates during severe hypoxia and reoxygenation in sheep in vivo. Graded hypoxia was performed in open-chested sheep to adjust PO2 to values where rapid depletion of energy stores occurred. Highly time-resolved 31P nuclear magnetic resonance spectroscopy enabled monitoring of myocardial phosphates throughout hypoxia and recovery with simultaneous MVO2 measurement. Sheep undergoing graded hypoxia (n = 5) with an arterial PO2 nadir of 13.4 +/- 0.5 mmHg, demonstrated maintained rates of oxygen consumption with large changes in coronary flow as phosphocreatine (PCr) decreased within 4 min to 40 +/- 7% of baseline. ATP utilization rate increased simultaneously 59 +/- 20%. Recovery was accompanied by marked increases in MVO2 from 2.0 +/- 0.5 to 7.2 +/- 1.9 mumol/g per min, while PCr recovery rate was 4.3 +/- 0.6 mumol/g per min. ATP decreased to 75 +/- 6% of baseline during severe hypoxia and did not recover. Sheep (n = 5) which underwent moderate hypoxia (PO2 maintained 25-35 mmHg for 10 min) did not demonstrate change in PCr or ATP. Functional and work assessment (n = 4) revealed that cardiac power increased during the graded hypoxia and was maintained through early reoxygenation. These studies show that (a) MVO2 does not decrease during oxygen deprivation in vivo despite marked and rapid decreases in high energy phosphates; (b) contractile function during hypoxia in vivo does not decrease during periods of PCr depletion and intracellular phosphate accumulation, and this may be related to marked increases in circulating catecholamines during global hypoxia. The measured creatine rephosphorylation rate is 34 +/- 11% of predicted (P < 0.01) calculated from reoxygenation parameters, which indicates that some mitochondrial respiratory uncoupling also occurs during the rephosphorylation period. Images PMID:7738181

  17. Evaluation of sexual function outcomes in women undergoing vaginal rejuvenation/vaginoplasty procedures for symptoms of vaginal laxity/decreased vaginal sensation utilizing validated sexual function questionnaire (PISQ-12).

    PubMed

    Moore, Robert D; Miklos, John R; Chinthakanan, Orawee

    2014-03-01

    Sexual function outcomes were analyzed in a group of women (n = 78) presenting for vaginal rejuvenation/vaginoplasty procedure for a chief complaint of vaginal laxity and decreased sensation with intercourse. Outcomes were analyzed utilizing the validated Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) before and at least 6 months after repair with vaginal rejuvenation/vaginoplasty procedure (VR). Mean age was 43.6 ± 7.9 (range 25-62), and 19 patients (24.3%) were found to have prolapse at time of initial exam and underwent vaginal vault suspension in addition to VR. Compared preoperatively and postoperatively, the overall sexual function (Total PISQ-12) statistically improved (30.3 ± 6.6 vs. 38.2 ± 5.2, P < 0.001). All individual scores statistically improved except in 3 categories in which there was no change (Q1-desire, Q5-pain, and Q11- partner premature ejaculation). Overall sexual satisfaction improved as well as subcategories of increased sexual excitement during intercourse and overall increase in intensity of orgasms. Pain with intercourse subscores were found to be no different from preoperatively to postoperatively. Previous studies have shown that sexual function improves with repair of prolapse; however, this is the first study to show improved function using a validated questionnaire in patients undergoing VR for laxity.

  18. A Classroom Mathematics Utility.

    ERIC Educational Resources Information Center

    Williams, Michael

    1984-01-01

    Reviews CATUSPLOT, a mathematics utility aimed at high school algebra through college-level calculus. Basic program capabilities include plotting, tabulating, integrating, and locating of intersections of functions composed of combinations of polynomial, trigonometric, and exponential functions. Rated excellent on all areas examined…

  19. Defined Syllabuses in Modern Languages

    ERIC Educational Resources Information Center

    Harding, Ann; Honnor, Sylvia

    1974-01-01

    The advantages of a defined syllabus in second language teaching, especially in relation to public examinations, are discussed. The origin and development of the York defined syllabuses are described, and extracts are given from the introductory document and the French and Russian syllabuses. (RM)

  20. Clarifying and Defining Library Services.

    ERIC Educational Resources Information Center

    Shubert, Joseph F., Ed.; Josey, E. J., Ed.

    1991-01-01

    This issue presents articles which, in some way, help to clarify and define library services. It is hoped that this clarification in library service will serve to secure the resources libraries need to serve the people of New York. The following articles are presented: (1) Introduction: "Clarifying and Defining Library Services" (Joseph F.…

  1. Naturally occurring 2-substituted (1,3)-beta-D-glucan producing Lactobacillus suebicus and Pediococcus parvulus strains with potential utility in the production of functional foods.

    PubMed

    Garai-Ibabe, Gaizka; Dueñas, María Teresa; Irastorza, Ana; Sierra-Filardi, Elena; Werning, María Laura; López, Paloma; Corbí, Angel Luis; Fernández de Palencia, Pilar

    2010-12-01

    We have isolated three lactic acid bacteria (Lactobacillus suebicus CUPV221, Pediococcus parvulus CUPV1 and P. parvulus CUPV22) that produced high levels of 2-substituted (1,3)-beta-D-glucans which increased the viscosity of the growth media. The (1,3)-beta-D-glucan consisted of two main molecular species, with masses of approximately 10(7) and 10(4) Da, whose proportions varied among the strains. The three strains survived exposure to saliva and simulated gastric conditions at pH 5, with P. parvulus CUPV22 surviving at pH 3.1, and L. suebicus CUPV221 surviving at pH 1.8. All strains were resistant to pancreatin and bile salts. P. parvulus CUPV22 exhibited the highest adhesion (10.5%) to Caco-2 cells, which decreased to 1.2% after washing the cells. Finally, P. parvulus CUPV22 and L. suebicus CUPV221 induced the production of inflammation-related cytokines by polarized macrophages, and interestingly, L. suebicus stimulated the production of cytokine IL-10. These results indicate that the three strains have potential utility for the production of functional foods. PMID:20691585

  2. Advanced Power Electronic Interfaces for Distributed Energy Systems, Part 2: Modeling, Development, and Experimental Evaluation of Advanced Control Functions for Single-Phase Utility-Connected Inverter

    SciTech Connect

    Chakraborty, S.; Kroposki, B.; Kramer, W.

    2008-11-01

    Integrating renewable energy and distributed generations into the Smart Grid architecture requires power electronic (PE) for energy conversion. The key to reaching successful Smart Grid implementation is to develop interoperable, intelligent, and advanced PE technology that improves and accelerates the use of distributed energy resource systems. This report describes the simulation, design, and testing of a single-phase DC-to-AC inverter developed to operate in both islanded and utility-connected mode. It provides results on both the simulations and the experiments conducted, demonstrating the ability of the inverter to provide advanced control functions such as power flow and VAR/voltage regulation. This report also analyzes two different techniques used for digital signal processor (DSP) code generation. Initially, the DSP code was written in C programming language using Texas Instrument's Code Composer Studio. In a later stage of the research, the Simulink DSP toolbox was used to self-generate code for the DSP. The successful tests using Simulink self-generated DSP codes show promise for fast prototyping of PE controls.

  3. Paleontological evidence for defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Barnosky, A. D.

    2012-12-01

    Paleontological criteria formed the basis for defining most of the geological eras, periods, epochs, and ages that are commonly recognized. By the same token, the Anthropocene can be defined by paleontological distinctiveness in accordance with commonly accepted biostratigraphic and biochronologic practice. Here I focus on the utility of defining the Anthropocene by the distinctive fossils (or potential fossils of the future) that have accumulated and are accumulating in the sedimentary record. I discuss what kinds of biostratrigraphic criteria would be of most use in recognizing the Anthropocene's base and temporal extent, including pros and cons of definitions based on range zones, interval zones, lineage zones, assemblage zones, and abundance zones, as well as implications for potential reference sections. Key paleontological criteria useful in formally defining the Anthropocene as a geological epoch include (1) anthropogenic trace fossils such as buildings, roads, plastics, etc; (2) abundance zones based on remains of domesticated species and humans; and (3) assemblage zones based on species transported around the globe by people. The magnitude of paleontologically-recognizable changes that have occurred since humans became the dominant species on Earth is at least as great as the paleontological differences that distinguish other Cenozoic epochs, and supports recognition of the Anthropocene as a formal stratigraphic unit.

  4. Utility straight sections

    SciTech Connect

    Leemann, B.; Peggs, S.; Peterson, J.

    1985-10-01

    Utility straight sections are insertions in the SSC lattice to provide relatively free space to facilitate various beam manipulations. These uses include beam-abort, injection (and conceivably ejection), space for the rf system, and collimation. A typical utility straight section is 1500 meters in overall length (ranging from 500 to 1200 meters). It has zero dispersion and high values of the beta functions. The betatron phase shift across the insertion is about 90{degrees} in each plane.

  5. Annotating user-defined abstractions for optimization

    SciTech Connect

    Quinlan, D; Schordan, M; Vuduc, R; Yi, Q

    2005-12-05

    This paper discusses the features of an annotation language that we believe to be essential for optimizing user-defined abstractions. These features should capture semantics of function, data, and object-oriented abstractions, express abstraction equivalence (e.g., a class represents an array abstraction), and permit extension of traditional compiler optimizations to user-defined abstractions. Our future work will include developing a comprehensive annotation language for describing the semantics of general object-oriented abstractions, as well as automatically verifying and inferring the annotated semantics.

  6. Photovoltaics and electric utilities

    NASA Astrophysics Data System (ADS)

    Bright, R.; Leigh, R.; Sills, T.

    1981-12-01

    The long term value of grid connected, residential photovoltaic (PV) systems is determined. The value of the PV electricity is defined as the full avoided cost in accordance with the Public Utilities Regulatory Policies Act of 1978. The avoided cost is computed using a long range utility planning approach to measure revenue requirement changes in response to the time phased introduction of PV systems into the grid. A case study approach to three utility systems is used. The changing value of PV electricity over a twenty year period from 1985 is presented, and the fuel and capital savings due to FY are analyzed. These values are translated into measures of breakeven capital investment under several options of power interchange and pricing.

  7. The Problem of Defining Intelligence.

    ERIC Educational Resources Information Center

    Lubar, David

    1981-01-01

    The major philosophical issues surrounding the concept of intelligence are reviewed with respect to the problems surrounding the process of defining and developing artificial intelligence (AI) in computers. Various current definitions and problems with these definitions are presented. (MP)

  8. Defining proprioceptive behaviors for autonomous mobile robots

    NASA Astrophysics Data System (ADS)

    Overholt, James L.; Hudas, Greg R.; Gerhart, Grant R.

    2002-07-01

    Proprioception is a sense of body position and movement that supports the control of many automatic motor functions such as posture and locomotion. This concept, normally relegated to the fields of neural physiology and kinesiology, is being utilized in the field of unmanned mobile robotics. This paper looks at developing proprioceptive behaviors for use in controlling an unmanned ground vehicle. First, we will discuss the field of behavioral control of mobile robots. Next, a discussion of proprioception and the development of proprioceptive sensors will be presented. We will then focus on the development of a unique neural-fuzzy architecture that will be used to incorporate the control behaviors coming directly from the proprioceptive sensors. Finally we will present a simulation experiment where a simple multi-sensor robot, utilizing both external and proprioceptive sensors, is presented with the task of navigating an unknown terrain to a known target position. Results of the mobile robot utilizing this unique fusion methodology will be discussed.

  9. Lighting Utilization.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with lighting utilization. Its objective is for the student to be able to outline the development of lighting use and conservation and identify major types and operating characteristics of lamps used in electric lighting. Some topics…

  10. Estimating health-state utility values for patients with recurrent ovarian cancer using Functional Assessment of Cancer Therapy – General mapping algorithms

    PubMed Central

    Hettle, Robert; Borrill, John; Suri, Gaurav; Wulff, Jerome

    2015-01-01

    Objectives In the absence of EuroQol 5D data, mapping algorithms can be used to predict health-state utility values (HSUVs) for use in economic evaluation. In a placebo-controlled Phase II study of olaparib maintenance therapy (NCT00753545), health-related quality of life was measured using the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) questionnaire. Our objective was to generate HSUVs from the FACT-O data using published mapping algorithms. Materials and methods Algorithms were identified from a review of the literature. Goodness-of-fit and patient characteristics were compared to select the best-performing algorithm, and this was used to generate base-case HSUVs for the intention-to-treat population of the olaparib study and for patients with breast cancer antigen mutations. Results Four FACT – General (the core component of FACT-O) mapping algorithms were identified and compared. Under the preferred algorithm, treatment-related adverse events had no statistically significant effect on HSU (P>0.05). Discontinuation of the study treatment and breast cancer antigen mutation status were both associated with a reduction in HSUVs (–0.06, P=0.0009; and –0.03, P=0.0511, respectively). The mean HSUV recorded at assessment visits was 0.786. Conclusion FACT – General mapping generated credible HSUVs for an economic evaluation of olaparib. As reported in other studies, different algorithms may produce significantly different estimates of HSUV. For this reason, it is important to test whether the choice of a specific algorithm changes the conclusions of an economic evaluation. PMID:26648747

  11. Long-term functional outcome and donor-site morbidity associated with autogenous iliac crest bone grafts utilizing a modified anterior approach.

    PubMed

    Singh, Jaspal Ricky; Nwosu, Uzoma; Egol, Kenneth A

    2009-01-01

    Prior studies and techniques for harvesting iliac crest bone have shown significant postoperative pain, disability, and poor cosmesis. This retrospective study was conducted to examine bone graft donor-site morbidity by evaluating functional outcomes in patients who have undergone a modified anterior harvesting approach. The medical charts and hospital records of 43 patients were retrospectively reviewed over a 6-year period. Demographic information, operative notes, laboratory results, and the American Society of Anesthesiologists (ASA) classification were recorded. All patients were evaluated retrospectively at a mean 41 months after bone-graft harvesting. Patients available for follow-up were asked to quantify their pain level at the donor-site on a visual analog pain scale (0-10). They also completed SMFA forms, as well as a survey pertaining to sensory deficits, gait disturbances, and cosmetic appearance. Forty-four patients met the inclusion criteria consisting of 25 males and 18 females, mean age 47 years (range, 22 to 80 years). A total of 32 (73%) patients were available for long-term follow-up at a mean of 41.3 months (range, 8 to 83 months). Eight (25%) of these patients reported minimal postoperative pain at time of follow-up. Three of 32 (9%) patients reported minor ambulation difficulty as a result of donor-site pain. Other minor complications included hypertrophic scar formation (7%) and hematoma/seroma (3%). There were no major complications reported, such as deformity at the crest site (0%) or infection (0%). SMFA scores demonstrated a mean dysfunction score of 48.5 (range, 41.8 to 71.1) and a bother index of mean 47.9 (range, 42.6 to 73.9). Utilizing the anterior approach in iliac crest bone harvesting provides an abundant supply of both cortical and cancellous bone, an aesthetically favorable scar, and decreased postoperative donor-site pain. There were very few complications seen in our cohort as compared to previous studies with very good long

  12. Adaptable formations utilizing heterogeneous unmanned systems

    NASA Astrophysics Data System (ADS)

    Barnes, Laura E.; Garcia, Richard; Fields, MaryAnne; Valavanis, Kimon

    2009-05-01

    This paper addresses the problem of controlling and coordinating heterogeneous unmanned systems required to move as a group while maintaining formation. We propose a strategy to coordinate groups of unmanned ground vehicles (UGVs) with one or more unmanned aerial vehicles (UAVs). UAVs can be utilized in one of two ways: (1) as alpha robots to guide the UGVs; and (2) as beta robots to surround the UGVs and adapt accordingly. In the first approach, the UAV guides a swarm of UGVs controlling their overall formation. In the second approach, the UGVs guide the UAVs controlling their formation. The unmanned systems are brought into a formation utilizing artificial potential fields generated from normal and sigmoid functions. These functions control the overall swarm geometry. Nonlinear limiting functions are defined to provide tighter swarm control by modifying and adjusting a set of control variables forcing the swarm to behave according to set constraints. Formations derived are subsets of elliptical curves but can be generalized to any curvilinear shape. Both approaches are demonstrated in simulation and experimentally. To demonstrate the second approach in simulation, a swarm of forty UAVs is utilized in a convoy protection mission. As a convoy of UGVs travels, UAVs dynamically and intelligently adapt their formation in order to protect the convoy of vehicles as it moves. Experimental results are presented to demonstrate the approach using a fully autonomous group of three UGVs and a single UAV helicopter for coordination.

  13. Defining "Folklore" in the Classroom.

    ERIC Educational Resources Information Center

    Falke, Anne

    Folklore, a body of traditional beliefs of a people conveyed orally or by means of custom, is very much alive, involves all people, and is not the study of popular culture. In studying folklore, the principal tasks of the folklorist have been defined as determining definition, classification, source (the folk), origin (who composed folklore),…

  14. Defining and Measuring Psychomotor Performance

    ERIC Educational Resources Information Center

    Autio, Ossi

    2007-01-01

    Psychomotor performance is fundamental to human existence. It is important in many real world activities and nowadays psychomotor tests are used in several fields of industry, army, and medical sciences in employee selection. This article tries to define psychomotor activity by introducing some psychomotor theories. Furthermore the…

  15. Burnout and health care utilization.

    PubMed

    Jackson, C N; Manning, M R

    1995-01-01

    This study explores the relationship between burnout and health care utilization of 238 employed adults. Burnout was measured by the Maslach Burnout Inventory and health care utilization by insurance company records regarding these employees' health care costs and number of times they accessed health care services over a one year period. ANOVAs were conducted using Golembiewski and Munzenrider's approach to define the burnout phase. Significant differences in health care costs were found. PMID:10152340

  16. Detectability of auditory signals presented without defined observation intervals

    NASA Technical Reports Server (NTRS)

    Watson, C. S.; Nichols, T. L.

    1976-01-01

    Ability to detect tones in noise was measured without defined observation intervals. Latency density functions were estimated for the first response following a signal and, separately, for the first response following randomly distributed instances of background noise. Detection performance was measured by the maximum separation between the cumulative latency density functions for signal-plus-noise and for noise alone. Values of the index of detectability, estimated by this procedure, were approximately those obtained with a 2-dB weaker signal and defined observation intervals. Simulation of defined- and non-defined-interval tasks with an energy detector showed that this device performs very similarly to the human listener in both cases.

  17. Defining the Polar Field Reversal

    NASA Technical Reports Server (NTRS)

    Upton, Lisa; Hathaway, David H.

    2013-01-01

    The polar fields on the Sun are directly related to solar cycle variability. Recently there has been interest in studying an important characteristic of the polar fields: the timing of the polar field reversals. However this characteristic has been poorly defined, mostly due to the limitations of early observations. In the past, the reversals have been calculated by averaging the flux above some latitude (i.e. 55deg or 75deg). Alternatively, the reversal could be defined by the time in which the previous polarity is completely canceled and replaced by the new polarity at 90de, precisely at the pole. We will use a surface flux transport model to illustrate the differences in the timing of the polar field reversal based on each of these definitions and propose standardization in the definition of the polar field reversal. The ability to predict the timing of the polar field reversal using a surface flux transport model will also be discussed.

  18. How do people define moderation?

    PubMed

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. PMID:26964691

  19. How do people define moderation?

    PubMed

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight.

  20. Software-defined Quantum Communication Systems

    SciTech Connect

    Humble, Travis S; Sadlier, Ronald J

    2014-01-01

    Quantum communication systems harness modern physics through state-of-the-art optical engineering to provide revolutionary capabilities. An important concern for quantum communication engineering is designing and prototyping these systems to prototype proposed capabilities. We apply the paradigm of software-defined communica- tion for engineering quantum communication systems to facilitate rapid prototyping and prototype comparisons. We detail how to decompose quantum communication terminals into functional layers defining hardware, software, and middleware concerns, and we describe how each layer behaves. Using the super-dense coding protocol as a test case, we describe implementations of both the transmitter and receiver, and we present results from numerical simulations of the behavior. We find that while the theoretical benefits of super dense coding are maintained, there is a classical overhead associated with the full implementation.

  1. Structure-function dissection of Myxococcus xanthus CarD N-terminal domain, a defining member of the CarD_CdnL_TRCF family of RNA polymerase interacting proteins.

    PubMed

    Bernal-Bernal, Diego; Gallego-García, Aránzazu; García-Martínez, Gema; García-Heras, Francisco; Jiménez, María Angeles; Padmanabhan, S; Elías-Arnanz, Montserrat

    2015-01-01

    Two prototypes of the large CarD_CdnL_TRCF family of bacterial RNA polymerase (RNAP)-binding proteins, Myxococcus xanthus CarD and CdnL, have distinct functions whose molecular basis remain elusive. CarD, a global regulator linked to the action of several extracytoplasmic function (ECF) σ-factors, binds to the RNAP β subunit (RNAP-β) and to protein CarG via an N-terminal domain, CarDNt, and to DNA via an intrinsically unfolded C-terminal domain resembling eukaryotic high-mobility-group A (HMGA) proteins. CdnL, a CarDNt-like protein that is essential for cell viability, is implicated in σA-dependent rRNA promoter activation and interacts with RNAP-β but not with CarG. While the HMGA-like domain of CarD by itself is inactive, we find that CarDNt has low but observable ability to activate ECF σ-dependent promoters in vivo, indicating that the C-terminal DNA-binding domain is required to maximize activity. Our structure-function dissection of CarDNt reveals an N-terminal, five-stranded β -sheet Tudor-like domain, CarD1-72, whose structure and contacts with RNAP-β mimic those of CdnL. Intriguingly, and in marked contrast to CdnL, CarD mutations that disrupt its interaction with RNAP-β did not annul activity. Our data suggest that the CarDNt C-terminal segment, CarD61-179, may be structurally distinct from its CdnL counterpart, and that it houses at least two distinct and crucial function determinants: (a) CarG-binding, which is specific to CarD; and (b) a basic residue stretch, which is also conserved and functionally required in CdnL. This study highlights the evolution of shared and divergent interactions in similar protein modules that enable the distinct activities of two related members of a functionally important and widespread bacterial protein family.

  2. Structure-Function Dissection of Myxococcus xanthus CarD N-Terminal Domain, a Defining Member of the CarD_CdnL_TRCF Family of RNA Polymerase Interacting Proteins

    PubMed Central

    Bernal-Bernal, Diego; Gallego-García, Aránzazu; García-Martínez, Gema; García-Heras, Francisco; Jiménez, María Angeles; Padmanabhan, S.; Elías-Arnanz, Montserrat

    2015-01-01

    Two prototypes of the large CarD_CdnL_TRCF family of bacterial RNA polymerase (RNAP)-binding proteins, Myxococcus xanthus CarD and CdnL, have distinct functions whose molecular basis remain elusive. CarD, a global regulator linked to the action of several extracytoplasmic function (ECF) σ-factors, binds to the RNAP β subunit (RNAP-β) and to protein CarG via an N-terminal domain, CarDNt, and to DNA via an intrinsically unfolded C-terminal domain resembling eukaryotic high-mobility-group A (HMGA) proteins. CdnL, a CarDNt-like protein that is essential for cell viability, is implicated in σA-dependent rRNA promoter activation and interacts with RNAP-β but not with CarG. While the HMGA-like domain of CarD by itself is inactive, we find that CarDNt has low but observable ability to activate ECF σ-dependent promoters in vivo, indicating that the C-terminal DNA-binding domain is required to maximize activity. Our structure-function dissection of CarDNt reveals an N-terminal, five-stranded β -sheet Tudor-like domain, CarD1–72, whose structure and contacts with RNAP-β mimic those of CdnL. Intriguingly, and in marked contrast to CdnL, CarD mutations that disrupt its interaction with RNAP-β did not annul activity. Our data suggest that the CarDNt C-terminal segment, CarD61–179, may be structurally distinct from its CdnL counterpart, and that it houses at least two distinct and crucial function determinants: (a) CarG-binding, which is specific to CarD; and (b) a basic residue stretch, which is also conserved and functionally required in CdnL. This study highlights the evolution of shared and divergent interactions in similar protein modules that enable the distinct activities of two related members of a functionally important and widespread bacterial protein family. PMID:25811865

  3. Evaluating the laws defining blindness.

    PubMed

    Hoppe, E

    1992-06-01

    The law defining legal blindness was written in 1935, and has not been updated since. A historical view of the background in the development of this law and a comparison to laws used in other countries helps to point out some problems with the current definition. As the population gets older, the prevalence of visual impairment will be increasing. To administer programs, distribute funding, and ensure adequate care, the problems inherent in the definition of legal blindness must be addressed, and the law must be revised. PMID:1634739

  4. Software-defined reconfigurable microwave photonics processor.

    PubMed

    Pérez, Daniel; Gasulla, Ivana; Capmany, José

    2015-06-01

    We propose, for the first time to our knowledge, a software-defined reconfigurable microwave photonics signal processor architecture that can be integrated on a chip and is capable of performing all the main functionalities by suitable programming of its control signals. The basic configuration is presented and a thorough end-to-end design model derived that accounts for the performance of the overall processor taking into consideration the impact and interdependencies of both its photonic and RF parts. We demonstrate the model versatility by applying it to several relevant application examples.

  5. Improvement in functional characteristics of aluminum-silicon cast components through the utilization of a novel electromagnetic treatment of liquid melts

    NASA Astrophysics Data System (ADS)

    Robles Hernandez, Francisco Carlos

    ML. Additionally, this SiML, Vickers microhardness and Brinell hardness presented similar behaviour as a function of the ESV melt treatment conditions. The SiML increased from 4.3 to 7.7 and the microhardness increased up to 35% in heat treated test samples, while Brinell hardness increased 25%. Using multiple regression analysis a correlation between the ESV melt treatment conditions, the results of TA, SiML and Vickers and Brinell hardness was established. With multiple regression analysis, several algorithms were developed to predict the SiML or mechanical properties based on the ESV melt treatment conditions or the TA results. These algorithms are a powerful tool for on line determination of the SiML of the mechanical properties of ESV treated castings. The tensile properties of the ESV treated melts were determined in test bars cast in the Stahl mould. The ESV melt treated test samples presented an improvement of ˜20% in as cast conditions and ˜30% after the heat treatment. A fractography analysis of the test bars was conducted and was found that the primary Si and the shrinkage pores are responsible for the lower mechanical properties of the test bars cast with untreated melt. Additionally, the improvement of the tensile properties of the ESV melt treated samples was due to the elimination of the porosity and the highly refined Si due to the melt treatment. The ESV treated melts were utilized to cast prototype pistons and cylinder liners. The cylinder liners were used to produce prototype V6 engine blocks. The prototype engine blocks were cast at NEMAK of Canada Corporation with cast in prototype Al-Si cylinder liners. The mechanical characteristics and the microstructure were evaluated following Ford's Materials Specifications for cylinder liners and regular production engine blocks in the bulkhead sections. Soundness (porosity) and mechanical properties in the V6 prototype engine blocks were assessed in comparison to the regular production engine block. The porosity

  6. Defining Child Neglect Based on Child Protective Services Data

    ERIC Educational Resources Information Center

    Dubowitz, H.; Pitts, S.C.; Litrownik, A.J.; Cox, C.E.; Runyan, D.; Black, M.M.

    2005-01-01

    Objectives:: To compare neglect defined by Child Protective Services official codes with neglect defined by a review of CPS narrative data, and to examine the validity of the different neglect measures using children's functioning at age 8 years. Methods:: Data are from 740 children participating in a consortium of longitudinal studies on child…

  7. Defining Life: The Virus Viewpoint

    NASA Astrophysics Data System (ADS)

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  8. Defining life: the virus viewpoint.

    PubMed

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism-the virus-producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  9. Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of "A-β+" ketosis-prone diabetes based on long-term β-cell function, human leukocyte antigen class II alleles, and sex predilection.

    PubMed

    Nalini, Ramaswami; Ozer, Kerem; Maldonado, Mario; Patel, Sanjeet G; Hampe, Christiane S; Guthikonda, Anu; Villanueva, Jesus; O'Brian Smith, E; Gaur, Lakshmi K; Balasubramanyam, Ashok

    2010-10-01

    Ketosis-prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with "A-β+" KPD (absent autoantibodies and preserved β-cell function) segregated into 2 subgroups with distinct evolution of β-cell function and glycemic control. Generalized linear analysis demonstrated that the variable that most significantly differentiated them was presence of a clinically evident precipitating event for the index diabetic ketoacidosis (DKA). Hence, we performed a comprehensive analysis of A-β+ KPD patients presenting with "provoked" compared with "unprovoked" DKA. Clinical, biochemical, and β-cell functional characteristics were compared between provoked and unprovoked A-β+ KPD patients followed prospectively for 1 to 8 years. Human leukocyte antigen class II allele frequencies were compared between these 2 groups and population controls. Unprovoked A-β+ KPD patients (n = 83) had greater body mass index, male preponderance, higher frequency of women with oligo-/anovulation, more frequent African American ethnicity, and less frequent family history of diabetes than provoked A-β+ KPD patients (n = 64). The provoked group had higher frequencies of the human leukocyte antigen class II type 1 diabetes mellitus susceptibility alleles DQB1*0302 (than the unprovoked group or population controls) and DRB1*04 (than the unprovoked group), whereas the unprovoked group had a higher frequency of the protective allele DQB1*0602. β-Cell secretory reserve and glycemic control improved progressively in the unprovoked group but declined in the provoked group. The differences persisted in comparisons restricted to patients with new-onset diabetes. "Unprovoked" A-β+ KPD is a distinct syndrome characterized by reversible β-cell dysfunction with male predominance and increased frequency of DQB1*0602, whereas "provoked" A-β+ KPD is characterized by progressive loss of β-cell reserve and increased frequency of DQB1*0302 and DRB1*04. Unprovoked DKA predicts long

  10. TWRS LDUA utilization study report

    SciTech Connect

    Rieck, R.H.

    1994-09-01

    Tank Waste Remediation Systems functional requirements were reviewed. The Light Duty Utility Arm capabilities were considered as a means to support completion of these functional requirements. The recommendation is made to continue to develop the LDUA, integrating TWRS functional needs into the design to better support completion of TWRS mission needs.

  11. Defining Life: Synthesis and Conclusions

    NASA Astrophysics Data System (ADS)

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. §1 defends that the recognition of “life” has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. §2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. §3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about “life”. The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (§4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. §5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions

  12. Defining life: synthesis and conclusions.

    PubMed

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. Section 1 defends that the recognition of "life" has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. Section 2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. Section 3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about "life". The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (Section 4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. Section 5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers

  13. Energy utilization in phonation

    NASA Astrophysics Data System (ADS)

    Krane, Michael

    2015-11-01

    A control volume analysis of energy utilization in phonation is presented. Conversion of subglottal airstream potential energy into work done vibrating the vocal folds, air flowing through the glottis, and radiating sound are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. An efficiency measure for each energy conversion mechanism is proposed. Acknowledge NIH grant 2R01 2R01DC005642.

  14. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes.

    PubMed

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational

  15. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes.

    PubMed

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔEAB. Counterpoise-corrected interaction energies ΔEAB are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A-B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [EMP2/CBS] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔECC-MP, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔEAB with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting deviation from the computational

  16. Density functional theory study of the interaction of vinyl radical, ethyne, and ethene with benzene, aimed to define an affordable computational level to investigate stability trends in large van der Waals complexes

    SciTech Connect

    Maranzana, Andrea E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Giordana, Anna E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it Indarto, Antonius Tonachini, Glauco; Barone, Vincenzo E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Causà, Mauro E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it; Pavone, Michele E-mail: anna.giordana@hotmail.com E-mail: mauro.causa@unina.it

    2013-12-28

    Our purpose is to identify a computational level sufficiently dependable and affordable to assess trends in the interaction of a variety of radical or closed shell unsaturated hydro-carbons A adsorbed on soot platelet models B. These systems, of environmental interest, would unavoidably have rather large sizes, thus prompting to explore in this paper the performances of relatively low-level computational methods and compare them with higher-level reference results. To this end, the interaction of three complexes between non-polar species, vinyl radical, ethyne, or ethene (A) with benzene (B) is studied, since these species, involved themselves in growth processes of polycyclic aromatic hydrocarbons (PAHs) and soot particles, are small enough to allow high-level reference calculations of the interaction energy ΔE{sub AB}. Counterpoise-corrected interaction energies ΔE{sub AB} are used at all stages. (1) Density Functional Theory (DFT) unconstrained optimizations of the A−B complexes are carried out, using the B3LYP-D, ωB97X-D, and M06-2X functionals, with six basis sets: 6-31G(d), 6-311 (2d,p), and 6-311++G(3df,3pd); aug-cc-pVDZ and aug-cc-pVTZ; N07T. (2) Then, unconstrained optimizations by Møller-Plesset second order Perturbation Theory (MP2), with each basis set, allow subsequent single point Coupled Cluster Singles Doubles and perturbative estimate of the Triples energy computations with the same basis sets [CCSD(T)//MP2]. (3) Based on an additivity assumption of (i) the estimated MP2 energy at the complete basis set limit [E{sub MP2/CBS}] and (ii) the higher-order correlation energy effects in passing from MP2 to CCSD(T) at the aug-cc-pVTZ basis set, ΔE{sub CC-MP}, a CCSD(T)/CBS estimate is obtained and taken as a computational energy reference. At DFT, variations in ΔE{sub AB} with basis set are not large for the title molecules, and the three functionals perform rather satisfactorily even with rather small basis sets [6-31G(d) and N07T], exhibiting

  17. Early emergence of three dopamine D1 receptor subtypes in vertebrates. Molecular phylogenetic, pharmacological, and functional criteria defining D1A, D1B, and D1C receptors in European eel Anguilla anguilla.

    PubMed

    Cardinaud, B; Sugamori, K S; Coudouel, S; Vincent, J D; Niznik, H B; Vernier, P

    1997-01-31

    The existence of dopamine D1C and D1D receptors in Xenopus and chicken, respectively, challenged the established duality (D1A and D1B) of the dopamine D1 receptor class in vertebrates. To ascertain the molecular diversity of this gene family in early diverging vertebrates, we isolated four receptor-encoding sequences from the European eel Anguilla anguilla. Molecular phylogeny assigned two receptor sequences (D1A1 and D1A2) to the D1A subtype, and a third receptor to the D1B subtype. Additional sequence was orthologous to the Xenopus D1C receptor and to several other previously unclassified fish D1-like receptors. When expressed in COS-7 cells, eel D1A and D1B receptors display affinity profiles for dopaminergic ligands similar to those of other known vertebrate homologues. The D1C receptor exhibits pharmacological characteristics virtually identical to its Xenopus homologue. Functionally, while all eel D1 receptors stimulate adenylate cyclase, the eel D1B receptor exhibits greater constitutive activity than either D1A or D1C receptors. Semiquantitative reverse transcription-polymerase chain reaction reveals the differential distribution of D1A1, D1A2, D1B, and D1C receptor mRNA within the hypothalamic-pituitary axis of the eel brain. Taken together, these data suggest that the D1A, D1B, and D1C receptors arose prior to the evolutionary divergence of fish and tetrapods and exhibit molecular, pharmacological, and functional attributes that unambiguously allow for their classification as distinct D1 receptor subtypes in the vertebrate phylum. PMID:9006917

  18. The multiple roles of light-harvesting chlorophyll a/b-protein complexes define structure and optimize function of Arabidopsis chloroplasts: a study using two chlorophyll b-less mutants.

    PubMed

    Kim, Eun-Ha; Li, Xiao-Ping; Razeghifard, Reza; Anderson, Jan M; Niyogi, Krishna K; Pogson, Barry J; Chow, Wah Soon

    2009-08-01

    The multiple roles of light-harvesting chlorophyll a/b-protein complexes in the structure and function of Arabidopsis chloroplasts were investigated using two chlorophyll b-less mutants grown under metal halide lamps with a significant far-red component. In ch1-3, all six light-harvesting proteins of photosystem (PS) II were greatly decreased; in ch1-3lhcb5, Lhcb5 was completely absent while the other five proteins were further decreased. The thylakoids of ch1-3 were less negatively-charged than the wild type, and those of ch1-3lhcb5 were even less so. Despite the expected weaker electrostatic repulsion, however, thylakoids in leaves of the mutants were not well stacked, an effect we attribute to lower van der Waals attraction, lower electrostatic attraction between opposite charges, and the absence or instability of PSII supercomplexes and peripheral light-harvesting trimers. The quantum yield of oxygen evolution in leaves decreased from 0.109 (wild type) to 0.087 (ch1-3) and 0.081 (ch1-3lhcb5) O(2) (photon absorbed)(-1); we attribute this decrease to an excessive spillover from PSII to PSI, a limited PSII antenna, and increased light-independent thermal dissipation in PSII in the mutants. Destabilization of the donor side of PSII, indicated by slower electron donation to the redox-active tyrosine Y(Z)(*) in ch1-3, probably enhanced PSII susceptibility to photoinactivation, increased the non-functional PSII complexes in vivo, and further inactivated PSII complexes in vitro. The evolution of chlorophyll b-containing chloroplasts seems to fine-tune oxygenic photosynthesis.

  19. Smooth Pursuit of Flicker-Defined Motion

    NASA Technical Reports Server (NTRS)

    Mulligan, Jeffrey B.; Stevenson, Scott B.

    2014-01-01

    We examined the pursuit response to stimuli defined by space-variant flicker of a dense random dot carrier pattern. On each frame, every element of the pattern could change polarity, with a probability given by a two-dimensional Gaussian distribution. A normal distribution produces a circular region of twinkle, while inverting the distribution results in a spot of static texture in a twinkling surround. In this latter case, the carrier texture could be stationary, or could move with the twinkle modulator, thereby producing first-order motion in the region of the spot. While the twinkle-defined spot produces a strong sensation of motion, the complementary stimulus defined by the absence of twinkle does not, when viewed peripherally, it appears to move in steps even when the generating distribution moves smoothly. We examined pursuit responses to these stimuli using two techniques: 1) the eye movement correlogram, obtained by cross-correlating eye velocity with the velocity of a randomly-moving stimulus; and 2) delayed visual feedback, where transient stabilization of a target can produce spontaneous oscillations of the eye, with a period empirically observed to vary linearly with the applied delay. Both techniques provide an estimate of the internal processing time, which can be as short as 100 milliseconds for a first-order target. Assessed by the correlogram method, the response to flicker-defined motion is delayed by more than 100 milliseconds, and significantly weaker (especially in the vertical dimension). When initially presented in the delayed feedback condition, purely saccadic oscillation is observed. One subject eventually developed smooth oscillations (albeit with significant saccadic intrusions), showing a period-versus-delay slope similar to that observed for first-order targets. This result is somewhat surprising, given that we interpret the slope of the period-versus-delay-function as reflecting the balance between position- and velocity

  20. Defining groundwater age: Chapter 3

    USGS Publications Warehouse

    Torgersen, T.; Purtschert, R.; Phillips, F.M.; Plummer, L.N.; Sanford, W.E.; Suckow, A.

    2013-01-01

    This book investigates applications of selected chemical and isotopic substances that can be used to recognize and interpret age information pertaining to ‘old’ groundwater (defined as water that was recharged on a timescale from approximately 1000 to more than 1 000 000 a). However, as discussed below, only estimates of the ‘age’ of water extracted from wells can be inferred. These groundwater age estimates are interpreted from measured concentrations of chemical and isotopic substances in the groundwater. Even then, there are many complicating factors, as discussed in this book. In spite of these limitations, much can be learned about the physics of groundwater flow and about the temporal aspects of groundwater systems from age interpretations of measured concentrations of environmental tracers in groundwater systems. This chapter puts the concept of ‘age’ into context, including its meaning and interpretation, and attempts to provide a unifying usage for the rest of the book.

  1. Defining biocultural approaches to conservation.

    PubMed

    Gavin, Michael C; McCarter, Joe; Mead, Aroha; Berkes, Fikret; Stepp, John Richard; Peterson, Debora; Tang, Ruifei

    2015-03-01

    We contend that biocultural approaches to conservation can achieve effective and just conservation outcomes while addressing erosion of both cultural and biological diversity. Here, we propose a set of guidelines for the adoption of biocultural approaches to conservation. First, we draw lessons from work on biocultural diversity and heritage, social-ecological systems theory, integrated conservation and development, co-management, and community-based conservation to define biocultural approaches to conservation. Second, we describe eight principles that characterize such approaches. Third, we discuss reasons for adopting biocultural approaches and challenges. If used well, biocultural approaches to conservation can be a powerful tool for reducing the global loss of both biological and cultural diversity.

  2. Factors Determining Roles and Functions of Educational Linking Agents with Implications for Training and Support Systems. Educational Knowledge, Dissemination, and Utilization: Occasional Paper Series.

    ERIC Educational Resources Information Center

    Butler, Matilda; Paisley, William

    Relationships are examined among linking functions and the linking agent role in the context of factors that determine the function and affect the role. The historical context in which educational dissemination has evolved is described, and three major clusters of dissemination concepts that have been identified and analyzed since 1966 are…

  3. Miniature EVA Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  4. Defined Media for H. pylori.

    PubMed

    Reynolds, D J

    1997-01-01

    Helicobacter pylori has been widely studied since its discovery in 1982 by Marshall and Warren (1), but many aspects of its structure, metabolism, and physiology, including its specific growth requirements, are still largely unknown, The organism is generally grown in complex media containing tissue extracts (e.g., of brain or heart) or proteolytic enzyme digests of meat or casein supplemented with blood or serum, which has made the metabolic pathways utilized by the bacterium difficult to determine. For example, although early studies based on acid formation from sugars and detection of preformed enzymes found no evidence of saccharide fermentative pathways (2,3), more recent evidence indicates that H. pylori does indeed catabolize sugars. In a series of studies, Mendz, Hazell, and colleagues found clear evidence for the pentose phosphate pathway (4), glucokinase activity (5), and the fermentation of glucose to lactate (6). PMID:21351021

  5. Using Bayesian Population Viability Analysis to Define Relevant Conservation Objectives.

    PubMed

    Green, Adam W; Bailey, Larissa L

    2015-01-01

    Adaptive management provides a useful framework for managing natural resources in the face of uncertainty. An important component of adaptive management is identifying clear, measurable conservation objectives that reflect the desired outcomes of stakeholders. A common objective is to have a sustainable population, or metapopulation, but it can be difficult to quantify a threshold above which such a population is likely to persist. We performed a Bayesian metapopulation viability analysis (BMPVA) using a dynamic occupancy model to quantify the characteristics of two wood frog (Lithobates sylvatica) metapopulations resulting in sustainable populations, and we demonstrate how the results could be used to define meaningful objectives that serve as the basis of adaptive management. We explored scenarios involving metapopulations with different numbers of patches (pools) using estimates of breeding occurrence and successful metamorphosis from two study areas to estimate the probability of quasi-extinction and calculate the proportion of vernal pools producing metamorphs. Our results suggest that ≥50 pools are required to ensure long-term persistence with approximately 16% of pools producing metamorphs in stable metapopulations. We demonstrate one way to incorporate the BMPVA results into a utility function that balances the trade-offs between ecological and financial objectives, which can be used in an adaptive management framework to make optimal, transparent decisions. Our approach provides a framework for using a standard method (i.e., PVA) and available information to inform a formal decision process to determine optimal and timely management policies.

  6. Using Bayesian Population Viability Analysis to Define Relevant Conservation Objectives

    PubMed Central

    Green, Adam W.; Bailey, Larissa L.

    2015-01-01

    Adaptive management provides a useful framework for managing natural resources in the face of uncertainty. An important component of adaptive management is identifying clear, measurable conservation objectives that reflect the desired outcomes of stakeholders. A common objective is to have a sustainable population, or metapopulation, but it can be difficult to quantify a threshold above which such a population is likely to persist. We performed a Bayesian metapopulation viability analysis (BMPVA) using a dynamic occupancy model to quantify the characteristics of two wood frog (Lithobates sylvatica) metapopulations resulting in sustainable populations, and we demonstrate how the results could be used to define meaningful objectives that serve as the basis of adaptive management. We explored scenarios involving metapopulations with different numbers of patches (pools) using estimates of breeding occurrence and successful metamorphosis from two study areas to estimate the probability of quasi-extinction and calculate the proportion of vernal pools producing metamorphs. Our results suggest that ≥50 pools are required to ensure long-term persistence with approximately 16% of pools producing metamorphs in stable metapopulations. We demonstrate one way to incorporate the BMPVA results into a utility function that balances the trade-offs between ecological and financial objectives, which can be used in an adaptive management framework to make optimal, transparent decisions. Our approach provides a framework for using a standard method (i.e., PVA) and available information to inform a formal decision process to determine optimal and timely management policies. PMID:26658734

  7. Using Bayesian Population Viability Analysis to Define Relevant Conservation Objectives.

    PubMed

    Green, Adam W; Bailey, Larissa L

    2015-01-01

    Adaptive management provides a useful framework for managing natural resources in the face of uncertainty. An important component of adaptive management is identifying clear, measurable conservation objectives that reflect the desired outcomes of stakeholders. A common objective is to have a sustainable population, or metapopulation, but it can be difficult to quantify a threshold above which such a population is likely to persist. We performed a Bayesian metapopulation viability analysis (BMPVA) using a dynamic occupancy model to quantify the characteristics of two wood frog (Lithobates sylvatica) metapopulations resulting in sustainable populations, and we demonstrate how the results could be used to define meaningful objectives that serve as the basis of adaptive management. We explored scenarios involving metapopulations with different numbers of patches (pools) using estimates of breeding occurrence and successful metamorphosis from two study areas to estimate the probability of quasi-extinction and calculate the proportion of vernal pools producing metamorphs. Our results suggest that ≥50 pools are required to ensure long-term persistence with approximately 16% of pools producing metamorphs in stable metapopulations. We demonstrate one way to incorporate the BMPVA results into a utility function that balances the trade-offs between ecological and financial objectives, which can be used in an adaptive management framework to make optimal, transparent decisions. Our approach provides a framework for using a standard method (i.e., PVA) and available information to inform a formal decision process to determine optimal and timely management policies. PMID:26658734

  8. The utility of captive animals in actualistic research: A geometric morphometric exploration of the tooth row of Alligator mississippiensis suggesting ecophenotypic influences and functional constraints.

    PubMed

    Drumheller, Stephanie K; Wilberg, Eric W; Sadleir, Rudyard W

    2016-07-01

    Captive broad snouted crocodylians are generally thought to have wider, shorter rostra than their wild counterparts. Interpreted to reflect morphological change in response to the conditions of captivity, this qualitative pattern could affect the utility of these animals in a variety of fields of research. However, due to relative ease of access and availability of life history data, captive animals are often utilized in actualistic research. Thus, this issue should be addressed in more detail. Here we explore snout shape variation between captive and wild members of Alligator mississippiensis using two-dimensional (2D) morphometric techniques. Several landmark schemesare used to assess the utility of different aspects of morphology in distinguishing the groups. While statistical analyses consistently differentiated between the groups, the area of morphospace occupied by wild members of A. mississippiensis generally overlapped with the larger area encompassing the captive specimens. This indicates that the captive condition is not as uniform as previously thought and instead encompasses a large spectrum of morphologies, ranging from the stereotypical broad, shortened snouts to outlines that are indistinguishable from the wild morphotype. These results align well with the interpretation that this change reflects an extreme example of ecophenotypy, since ranched, farmed, or zoo organisms are held in an array of enclosures, ranging from indoor, climate controlled pens to outdoor, more natural areas. This variation in environments should be reflected in different reactions to the animals' surroundings, resulting in a broad spectrum of morphotypes. While wild specimens are still preferred, especially for fine scale analyses, these results indicate that not all captive members of A. mississippiensis exhibit the extreme morphological alterations often cited in the literature. Weighing the conditions in which the animals are held and exploring the possibility of

  9. Defining a key receptor-CheA kinase contact and elucidating its function in the membrane-bound bacterial chemosensory array: a disulfide mapping and TAM-IDS Study.

    PubMed

    Piasta, Kene N; Ulliman, Caleb J; Slivka, Peter F; Crane, Brian R; Falke, Joseph J

    2013-06-01

    The three core components of the ubiquitous bacterial chemosensory array - the transmembrane chemoreceptor, the histidine kinase CheA, and the adaptor protein CheW - assemble to form a membrane-bound, hexagonal lattice in which receptor transmembrane signals regulate kinase activity. Both the regulatory domain of the kinase and the adaptor protein bind to overlapping sites on the cytoplasmic tip of the receptor (termed the protein interaction region). Notably, the kinase regulatory domain and the adaptor protein share the same fold constructed of two SH3-like domains. The present study focuses on the structural interface between the receptor and the kinase regulatory domain. Two models have been proposed for this interface: Model 1 is based on the crystal structure of a homologous Thermotoga complex between a receptor fragment and the CheW adaptor protein. This model has been used in current models of chemosensory array architecture to build the receptor-CheA kinase interface. Model 2 is based on a newly determined crystal structure of a homologous Thermotoga complex between a receptor fragment and the CheA kinase regulatory domain. Both models present unique strengths and weaknesses, and current evidence is unable to resolve which model best describes contacts in the native chemosensory arrays of Escherichia coli, Salmonella typhimurium, and other bacteria. Here we employ disulfide mapping and tryptophan and alanine mutation to identify docking sites (TAM-IDS) to test Models 1 and 2 in well-characterized membrane-bound arrays formed from E. coli and S. typhimurium components. The results reveal that the native array interface between the receptor protein interaction region and the kinase regulatory domain is accurately described by Model 2, but not by Model 1. In addition, the results show that the interface possesses both a structural function that contributes to stable CheA kinase binding in the array and a regulatory function central to transmission of the

  10. Strain energy release rate as a function of temperature and preloading history utilizing the edge delamination fatique test method. Contractor resepor, July 1986-October 1988

    SciTech Connect

    Zimmerman, R.S.; Adams, D.F.

    1989-02-01

    Static laminate and tension-tension fatigue tests of IM7/8551-7 composite materials was performed. The Edge Delamination Test (EDT) was utilized to evaluate the temperature and preloading history effect on the critical strain energy release rate. Static and fatigue testing was performed at room temperature and 180 F (82 C). Three preloading schemes were used to precondition fatigue test specimens prior to performing the normal tension-tension fatigue EDT testing. Computer software was written to perform all fatigue testing while monitoring the dynamic modulus to detect the onset of delamination and record the test information for later retrieval and reduction.

  11. Number series of atoms, interatomic bonds and interface bonds defining zinc-blende nanocrystals as function of size, shape and surface orientation: Analytic tools to interpret solid state spectroscopy data

    NASA Astrophysics Data System (ADS)

    König, Dirk

    2016-08-01

    Semiconductor nanocrystals (NCs) experience stress and charge transfer by embedding materials or ligands and impurity atoms. In return, the environment of NCs experiences a NC stress response which may lead to matrix deformation and propagated strain. Up to now, there is no universal gauge to evaluate the stress impact on NCs and their response as a function of NC size dNC. I deduce geometrical number series as analytical tools to obtain the number of NC atoms NNC(dNC[i]), bonds between NC atoms Nbnd(dNC[i]) and interface bonds NIF(dNC[i]) for seven high symmetry zinc-blende (zb) NCs with low-index faceting: {001} cubes, {111} octahedra, {110} dodecahedra, {001}-{111} pyramids, {111} tetrahedra, {111}-{001} quatrodecahedra and {001}-{111} quadrodecahedra. The fundamental insights into NC structures revealed here allow for major advancements in data interpretation and understanding of zb- and diamond-lattice based nanomaterials. The analytical number series can serve as a standard procedure for stress evaluation in solid state spectroscopy due to their deterministic nature, easy use and general applicability over a wide range of spectroscopy methods as well as NC sizes, forms and materials.

  12. Effect of acid scavengers on electrochemical performance of lithium-sulfur batteries: Functional additives for utilization of LiPF6

    NASA Astrophysics Data System (ADS)

    Yim, Taeeun; Kang, Kyoung Seok; Yu, Ji-Sang; Kim, Ki Jae; Park, Min-Sik; Woo, Sang-Gil; Jeong, Goojin; Jo, Yong Nam; Im, Keun Yung; Kim, Jae-Hun; Kim, Young-Jun

    2014-08-01

    We investigated a novel approach for utilizing LiPF6 as the lithium salt for Li-S batteries and verifying its chemical reactivity with the main solvent. It is found that the main obstacle for the adoption of LiPF6 is the undesired acid-catalyzed, cascade-type polymerization reaction between cyclic ether components in the solvent and LiPF6. Therefore, several kinds of acid scavengers are proposed to enhance the chemical stability between the main solvent and LiPF6. Simple storage tests indicate that polymerization occurred as acid residue is removed from the electrolyte. Consequently, the cell with a modified electrolyte shows excellent discharge capacity and moderate retention based on its improved chemical stability. These results indicate that assuring the chemical stability is the most important factor to utilizing LiPF6 as the main lithium salt for a Li-S cell. Additionally, it is believed that an understanding of the nature of chemical reactivity will be beneficial to constructing more efficient electrolyte systems owing to enhanced electrochemical performance of many kinds of energy storage systems including Li-S, Li-air, and metal-air batteries.

  13. A comparative study of family functioning, health, and mental health awareness and utilization among female Bedouin-Arabs from recognized and unrecognized villages in the Negev.

    PubMed

    Al-Krenawi, Alean; Graham, John R

    2006-02-01

    A good portion of geography is contested by the Israeli state and the country's Bedouin-Arab population. There are two categories of Bedouin villages: those areas that are "officially" recognized by the state and those that are not. In this article we determine utilization and awareness of health and mental health services among 376 Bedouin-Arab women in recognized and unrecognized villages in the Negev. Although there are differences between them, primary health care (PHC) services usually are available within recognized villages, accessible to those from unrecognized villages, and tend to precipitate user satisfaction. We conclude with various suggestions for improving health service delivery and making PHC and mental health delivery more accessible. Through this article we intend to help mental health practitioners on two levels: the policy level, regarding the design of mental health services for societies in transition, such as the Bedouin Arab, and the practical level by helping practitioners better appreciate the psychosocial status of women in Bedouin-Arab societies and the factors associated with Bedouin-Arab PHC utilization.

  14. Benthic Habitat-Based Framework for Ecological Production Functions: Case Study for Utilization by Estuarine Birds in a Northeast Pacific Estuary

    EPA Science Inventory

    Habitat-based frameworks have been proposed for developing Ecological Production Functions (EPFs) to describe the spatial distribution of ecosystem services. As proof of concept, we generated EPFs that compared bird use patterns among intertidal benthic habitats for Yaquina estu...

  15. Continuous utility factor in segregation models

    NASA Astrophysics Data System (ADS)

    Roy, Parna; Sen, Parongama

    2016-02-01

    We consider the constrained Schelling model of social segregation in which the utility factor of agents strictly increases and nonlocal jumps of the agents are allowed. In the present study, the utility factor u is defined in a way such that it can take continuous values and depends on the tolerance threshold as well as the fraction of unlike neighbors. Two models are proposed: in model A the jump probability is determined by the sign of u only, which makes it equivalent to the discrete model. In model B the actual values of u are considered. Model A and model B are shown to differ drastically as far as segregation behavior and phase transitions are concerned. In model A, although segregation can be achieved, the cluster sizes are rather small. Also, a frozen state is obtained in which steady states comprise many unsatisfied agents. In model B, segregated states with much larger cluster sizes are obtained. The correlation function is calculated to show quantitatively that larger clusters occur in model B. Moreover for model B, no frozen states exist even for very low dilution and small tolerance parameter. This is in contrast to the unconstrained discrete model considered earlier where agents can move even when utility remains the same. In addition, we also consider a few other dynamical aspects which have not been studied in segregation models earlier.

  16. Defining the Stimulus - A Memoir

    PubMed Central

    Terrace, Herbert

    2010-01-01

    The eminent psychophysicist, S. S. Stevens, once remarked that, “the basic problem of psychology was the definition of the stimulus” (Stevens, 1951, p. 46). By expanding the traditional definition of the stimulus, the study of animal learning has metamorphosed into animal cognition. The main impetus for that change was the recognition that it is often necessary to postulate a representation between the traditional S and R of learning theory. Representations allow a subject to re-present a stimulus it learned previously that is currently absent. Thus, in delayed-matching-to-sample, one has to assume that a subject responds to a representation of the sample during test if it responds correctly. Other examples, to name but a few, include concept formation, spatial memory, serial memory, learning a numerical rule, imitation and metacognition. Whereas a representation used to be regarded as a mentalistic phenomenon that was unworthy of scientific inquiry, it can now be operationally defined. To accommodate representations, the traditional discriminative stimulus has to be expanded to allow for the role of representations. The resulting composite can account for a significantly larger portion of the variance of performance measures than the exteroceptive stimulus could by itself. PMID:19969047

  17. Defining, Navigating, and Negotiating Success

    PubMed Central

    Kalet, Adina L; Fletcher, Kathlyn E; Ferdman, Dina J; Bickell, Nina A

    2006-01-01

    BACKGROUND We studied female graduates of the Robert Wood Johnson Clinical Scholars Program (CSP, Class of 1984 to 1989) to explore and describe the complexity of creating balance in the life of mid-career academic woman physicians. METHODS We conducted and qualitatively analyzed (κ 0.35 to 1.0 for theme identification among rater pairs) data from a semi-structured survey of 21 women and obtained their curricula vitae to quantify publications and grant support, measures of academic productivity. RESULTS Sixteen of 21 (76%) women completed the survey. Mean age was 48 (range: 45 to 56). Three were full professors, 10 were associate professors, and 3 had left academic medicine. Eleven women had had children (mean 2.4; range: 1 to 3) and 3 worked part-time. From these data, the conceptual model expands on 3 key themes: (1) defining, navigating, and negotiating success, (2) making life work, and (3) making work work. The women who described themselves as satisfied with their careers (10/16) had clarity of values and goals and a sense of control over their time. Those less satisfied with their careers (6/16) emphasized the personal and professional costs of the struggle to balance their lives and described explicit institutional barriers to fulfillment of their potential. CONCLUSION For this group of fellowship-prepared academic women physicians satisfaction is achieving professional and personal balance. PMID:16918735

  18. Glutathione Utilization by Candida albicans Requires a Functional Glutathione Degradation (DUG) Pathway and OPT7, an Unusual Member of the Oligopeptide Transporter Family

    PubMed Central

    Desai, Prashant Ramesh; Thakur, Anil; Ganguli, Dwaipayan; Paul, Sanjoy; Morschhäuser, Joachim; Bachhawat, Anand K.

    2011-01-01

    Candida albicans lacks the ability to survive within its mammalian host in the absence of endogenous glutathione biosynthesis. To examine the ability of this yeast to utilize exogenous glutathione, we exploited the organic sulfur auxotrophy of C. albicans met15Δ strains. We observed that glutathione is utilized efficiently by the alternative pathway of glutathione degradation (DUG pathway). The major oligopeptide transporters OPT1–OPT5 of C. albicans that were most similar to the known yeast glutathione transporters were not found to contribute to glutathione transport to any significant extent. A genomic library approach to identify the glutathione transporter of C. albicans yielded OPT7 as the primary glutathione transporter. Biochemical studies on OPT7 using radiolabeled GSH uptake revealed a Km of 205 μm, indicating that it was a high affinity glutathione transporter. OPT7 is unusual in several aspects. It is the most remote member to known yeast glutathione transporters, lacks the two highly conserved cysteines in the family that are known to be crucial in trafficking, and also has the ability to take up tripeptides. The transporter was regulated by sulfur sources in the medium. OPT7 orthologues were prevalent among many pathogenic yeasts and fungi and formed a distinct cluster quite remote from the Saccharomyces cerevisiae HGT1 glutathione transporter cluster. In vivo experiments using a systemic model of candidiasis failed to detect expression of OPT7 in vivo, and strains disrupted either in the degradation (dug3Δ) or transport (opt7Δ) of glutathione failed to show a defect in virulence. PMID:21994941

  19. Functional Analysis of Two l-Arabinose Transporters from Filamentous Fungi Reveals Promising Characteristics for Improved Pentose Utilization in Saccharomyces cerevisiae.

    PubMed

    Li, Jingen; Xu, Jing; Cai, Pengli; Wang, Bang; Ma, Yanhe; Benz, J Philipp; Tian, Chaoguang

    2015-06-15

    Limited uptake is one of the bottlenecks for l-arabinose fermentation from lignocellulosic hydrolysates in engineered Saccharomyces cerevisiae. This study characterized two novel l-arabinose transporters, LAT-1 from Neurospora crassa and MtLAT-1 from Myceliophthora thermophila. Although the two proteins share high identity (about 83%), they display different substrate specificities. Sugar transport assays using the S. cerevisiae strain EBY.VW4000 indicated that LAT-1 accepts a broad substrate spectrum. In contrast, MtLAT-1 appeared much more specific for l-arabinose. Determination of the kinetic properties of both transporters revealed that the Km values of LAT-1 and MtLAT-1 for l-arabinose were 58.12 ± 4.06 mM and 29.39 ± 3.60 mM, respectively, with corresponding Vmax values of 116.7 ± 3.0 mmol/h/g dry cell weight (DCW) and 10.29 ± 0.35 mmol/h/g DCW, respectively. In addition, both transporters were found to use a proton-coupled symport mechanism and showed only partial inhibition by d-glucose during l-arabinose uptake. Moreover, LAT-1 and MtLAT-1 were expressed in the S. cerevisiae strain BSW2AP containing an l-arabinose metabolic pathway. Both recombinant strains exhibited much faster l-arabinose utilization, greater biomass accumulation, and higher ethanol production than the control strain. In conclusion, because of higher maximum velocities and reduced inhibition by d-glucose, the genes for the two characterized transporters are promising targets for improved l-arabinose utilization and fermentation in S. cerevisiae.

  20. Defining disability: metaphysical not political.

    PubMed

    Riddle, Christopher A

    2013-08-01

    social model, unlike an interactional approach, is unable to provide a realistic account of the experience of disability, and subsequently, unable to be properly utilized to ensure justice for people with disabilities.

  1. Defining disability: metaphysical not political.

    PubMed

    Riddle, Christopher A

    2013-08-01

    social model, unlike an interactional approach, is unable to provide a realistic account of the experience of disability, and subsequently, unable to be properly utilized to ensure justice for people with disabilities. PMID:22481609

  2. Health-Related Quality of Life and Cognitive Functioning from the Perspective of Parents of School-Aged Children with Asperger's Syndrome Utilizing the PedsQL[TM

    ERIC Educational Resources Information Center

    Limbers, Christine A.; Heffer, Robert W.; Varni, James W.

    2009-01-01

    HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL[TM] 4.0 Generic Core Scales and PedsQL[TM] Cognitive Functioning Scale parent proxy-report versions in school-aged…

  3. Preservice Teachers' View on y = x + 5 and y= [pi]x[squared] Expressed through the Utilization of Concept Maps: A Study of the Concept of Function

    ERIC Educational Resources Information Center

    Hansson, Orjan

    2005-01-01

    This paper considers a group of preservice teachers' construction of concept maps derived from y = x + 5 and y = [pi]x[squared] with emphasis on their conceptual understanding of function. The two statements are perceived to represent a number of different concepts with indications of compartmentalized knowledge structures that might prevent the…

  4. Exploring the Utility of Background and Cognitive Variables in Explaining Latent Differential Item Functioning: An Example of the PISA 2009 Reading Assessment

    ERIC Educational Resources Information Center

    Chen, Ying-Fang; Jiao, Hong

    2014-01-01

    Differential item functioning (DIF) may be caused by an interaction of multiple manifest grouping variables or unexplored manifest variables, which cannot be detected by conventional DIF detection methods that are based on a single manifest grouping variable. Such DIF may be detected by a latent approach using the mixture item response theory…

  5. Utility of Language Comprehension Tests for Unintelligible or Non-Speaking Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

    Geytenbeek, Joke; Harlaar, Laurike; Stam, Marloes; Ket, Hans; Becher, Jules G.; Oostrom, Kim; Vermeulen, Jeroen

    2010-01-01

    Aim: To identify the use and utility of language comprehension tests for unintelligible or non-speaking children with severe cerebral palsy (CP). Method: Severe CP was defined as severe dysarthria (unintelligible speech) or anarthria (absence of speech) combined with severe limited mobility, corresponding to Gross Motor Function Classification…

  6. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

    PubMed Central

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

    2015-01-01

    Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

  7. Defining a Standard Metric for Electricity Savings

    SciTech Connect

    Brown, Marilyn; Akbari, Hashem; Blumstein, Carl; Koomey, Jonathan; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H.; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B.; Greenberg, Steve; Hafemeister, David; Harris, Jeff; Harvey, Hal; Heitz, Eric; Hirst, Eric; Hummel, Holmes; Kammen, Dan; Kelly, Henry; Laitner, Skip; Levine, Mark; Lovins, Amory; Masters, Gil; McMahon, James E.; Meier, Alan; Messenger, Michael; Millhone, John; Mills, Evan; Nadel, Steve; Nordman, Bruce; Price, Lynn; Romm, Joe; Ross, Marc; Rufo, Michael; Sathaye, Jayant; Schipper, Lee; Schneider, Stephen H; Sweeney, James L; Verdict, Malcolm; Vorsatz, Diana; Wang, Devra; Weinberg, Carl; Wilk, Richard; Wilson, John; Worrell, Ernst

    2009-03-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70percent capacity factor with 7percent T&D losses. Displacing such a plant for one year would save 3 billion kW h per year at the meter and reduce emissions by 3 million metric tons of CO2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question--Dr. Arthur H. Rosenfeld.

  8. Defining Neighborhood Boundaries for Urban Health Research

    PubMed Central

    Weiss, Linda; Ompad, Danielle; Galea, Sandro; Vlahov, David

    2008-01-01

    The body of literature exploring neighborhood effects on health has increased rapidly in recent years, yet a number of methodological concerns remain, including preferred methods for identification and delineation of study neighborhoods. In research combining census or other publicly available data with surveys of residents and/or street-level observations, questions regarding neighborhood definition take on added significance. Neighborhoods must be identified and delineated in such a way as to optimize quality and availability of data from each of these sources. IMPACT, a multi-level study examining associations between features of the urban environment and mental health, drug use, and sexual behavior, utilized a multi-step neighborhood definition process including development of census block group maps, review of land use and census tract data, and field visits and observation in each of the targeted communities. Field observations were guided by a pre-identified list of environmental features focused on the potential for recruitment (e.g. pedestrian volume); characteristics commonly used to define neighborhood boundaries (e.g. obstructions to pedestrian traffic, changes in land use), and characteristics that have been associated in the literature with health behaviors and health outcomes (such as housing type, maintenance and use of open spaces). This process, implemented in February through July 2005, proved feasible and offered the opportunity to identify neighborhoods appropriate to study objectives and to collect descriptive information that can be used as a context for understanding study results. PMID:17543706

  9. Evolutionary Conserved Positions Define Protein Conformational Diversity.

    PubMed

    Saldaño, Tadeo E; Monzon, Alexander M; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-03-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  10. Evolutionary Conserved Positions Define Protein Conformational Diversity

    PubMed Central

    Saldaño, Tadeo E.; Monzon, Alexander M.; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-01-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  11. Locally adaptive method to define coordination shell

    NASA Astrophysics Data System (ADS)

    Higham, Jonathan; Henchman, Richard H.

    2016-08-01

    An algorithm is presented to define a particle's coordination shell for any collection of particles. It requires only the particles' positions and no pre-existing knowledge or parameters beyond those already in the force field. A particle's shell is taken to be all particles that are not blocked by any other particle and not further away than a blocked particle. Because blocking is based on two distances and an angle for triplets of particles, it is called the relative angular distance (RAD) algorithm. RAD is applied to Lennard-Jones particles in molecular dynamics simulations of crystalline, liquid, and gaseous phases at various temperatures and densities. RAD coordination shells agree well with those from a cut-off in the radial distribution function for the crystals and liquids and are slightly higher for the gas.

  12. Locally adaptive method to define coordination shell.

    PubMed

    Higham, Jonathan; Henchman, Richard H

    2016-08-28

    An algorithm is presented to define a particle's coordination shell for any collection of particles. It requires only the particles' positions and no pre-existing knowledge or parameters beyond those already in the force field. A particle's shell is taken to be all particles that are not blocked by any other particle and not further away than a blocked particle. Because blocking is based on two distances and an angle for triplets of particles, it is called the relative angular distance (RAD) algorithm. RAD is applied to Lennard-Jones particles in molecular dynamics simulations of crystalline, liquid, and gaseous phases at various temperatures and densities. RAD coordination shells agree well with those from a cut-off in the radial distribution function for the crystals and liquids and are slightly higher for the gas. PMID:27586905

  13. Reconfigurable, Cognitive Software-Defined Radio

    NASA Technical Reports Server (NTRS)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  14. The Library Space Utilization Methodology.

    ERIC Educational Resources Information Center

    Hall, Richard B.

    1978-01-01

    Describes the Library Space Utilization (LSU) methodology, which demonstrates that significant information about the functional requirements of a library can be measured and displayed in a quantitative and graphic form. It measures "spatial" relationships between selected functional divisions; it also determines how many people--staff and…

  15. Health-related quality of life and cognitive functioning from the perspective of parents of school-aged children with Asperger's Syndrome utilizing the PedsQL.

    PubMed

    Limbers, Christine A; Heffer, Robert W; Varni, James W

    2009-11-01

    HRQOL as a multidimensional construct has not been previously investigated in children with Asperger's Syndrome. The objective of the present study was to examine the initial feasibility, reliability, and validity of the PedsQL 4.0 Generic Core Scales and PedsQL Cognitive Functioning Scale parent proxy-report versions in school-aged children with Asperger's Syndrome. The PedsQL evidenced no missing responses (0.0%), achieved excellent reliability for the Generic Core Total Scale score (alpha = 0.82) and Cognitive Functioning Scale (alpha = 0.92), distinguished between children with Asperger's Syndrome and a matched sample of healthy children, and was related to similar constructs on the Asperger Syndrome Diagnostic Scale. The results demonstrate the initial measurement properties of the PedsQL in school-aged children with Asperger's Syndrome.

  16. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    SciTech Connect

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.

  17. Structure-Function Analysis of Mammalian CYP2B Enzymes Using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism.

    PubMed

    Shah, Manish B; Liu, Jingbao; Huo, Lu; Zhang, Qinghai; Dearing, M Denise; Wilderman, P Ross; Szklarz, Grazyna D; Stout, C David; Halpert, James R

    2016-04-01

    Crystal structures of CYP2B35 and CYP2B37 from the desert woodrat were solved in complex with 4-(4-chlorophenyl)imidazole (4-CPI). The closed conformation of CYP2B35 contained two molecules of 4-CPI within the active site, whereas the CYP2B37 structure demonstrated an open conformation with three 4-CPI molecules, one within the active site and the other two in the substrate access channel. To probe structure-function relationships of CYP2B35, CYP2B37, and the related CYP2B36, we tested the O-dealkylation of three series of related substrates-namely, 7-alkoxycoumarins, 7-alkoxy-4-(trifluoromethyl)coumarins, and 7-alkoxy-4-methylcoumarins-with a C1-C7 side chain. CYP2B35 showed the highest catalytic efficiency (kcat/KM) with 7-heptoxycoumarin as a substrate, followed by 7-hexoxycoumarin. In contrast, CYP2B37 showed the highest catalytic efficiency with 7-ethoxy-4-(trifluoromethyl)coumarin (7-EFC), followed by