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. Defining functional dyspepsia.

    PubMed

    Mearin, Fermín; Calleja, José Luis

    2011-12-01

    Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand

  3. 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.

  4. 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.

  5. 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.

  6. Localization of functions defined on cantor group

    NASA Astrophysics Data System (ADS)

    Krivoshein, Aleksander V.; Lebedeva, Elena A.

    2013-10-01

    We introduce a notion of localization for dyadic functions, i. e. functions defined on Cantor group. Both non-periodic and periodic cases are discussed. Localization is characterized by functionals UCd and UCdp similar to the Heisenberg (the Breitenberger) uncertainty constants used for real-line (periodic) functions. We are looking for dyadic analogs of uncertainty principles. To justify definition we use some test functions including dyadic scaling and wavelet functions.

  7. 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.

  8. 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

  9. Defining the Orphan Functions of Lysine Acetyltransferases

    PubMed Central

    2016-01-01

    Long known for their role in histone acetylation, recent studies have demonstrated that lysine acetyltransferases also carry out distinct “orphan” functions. These activities impact a wide range of biological phenomena including metabolism, RNA modification, nuclear morphology, and mitochondrial function. Here, we review the discovery and characterization of orphan lysine acetyltransferase functions. In addition to highlighting the evidence and biological role for these functions in human disease, we discuss the part emerging chemical tools may play in investigating this versatile enzyme superfamily. PMID:25591746

  10. 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

  11. 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. PMID:25689187

  12. Considerations and challenges in defining optimal iron utilization in hemodialysis.

    PubMed

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

    2015-06-01

    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

  13. 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

  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. Role of histone modifications in defining chromatin structure and function.

    PubMed

    Gelato, Kathy A; Fischle, Wolfgang

    2008-04-01

    Chromosomes in eukaryotic cell nuclei are not uniformly organized, but rather contain distinct chromatin elements, with each state having a defined biochemical structure and biological function. These are recognizable by their distinct architectures and molecular components, which can change in response to cellular stimuli or metabolic requirements. Chromatin elements are characterized by the fundamental histone and DNA components, as well as other associated non-histone proteins and factors. Post-translational modifications of histone proteins in particular often correlate with a specific chromatin structure and function. Patterns of histone modifications are implicated as having a role in directing the level of chromatin compaction, as well as playing roles in multiple functional pathways directing the readout of distinct regions of the genome. We review the properties of various chromatin elements and the apparent links of histone modifications with chromatin organization and functional output. PMID:18225984

  16. 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

  17. 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

  18. Defining functional DNA elements in the human genome

    PubMed Central

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

    2014-01-01

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

  19. Subnetwork state functions define dysregulated subnetworks in cancer.

    PubMed

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

    2011-03-01

    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 fast 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 existing algorithms. Comprehensive cross-classification experiments show that subnetworks identified by Crane outperform those identified by additive algorithms in predicting metastasis of colorectal cancer (CRC). PMID:21385033

  20. 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

  1. 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. PMID:23574332

  2. 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.

  3. 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

  4. 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…

  5. 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.

  6. Swarm formation control utilizing elliptical surfaces and limiting functions.

    PubMed

    Barnes, Laura E; Fields, Mary Anne; Valavanis, Kimon P

    2009-12-01

    In this paper, we present a strategy for organizing swarms of unmanned vehicles into a formation by utilizing artificial potential fields that were generated from normal and sigmoid functions. These functions construct the surface on which swarm members travel, controlling the overall swarm geometry and the individual member spacing. Nonlinear limiting functions are defined to provide tighter swarm control by modifying and adjusting a set of control variables that force the swarm to behave according to set constraints, formation, and member spacing. The artificial potential functions and limiting functions are combined to control swarm formation, orientation, and swarm movement as a whole. Parameters are chosen based on desired formation and user-defined constraints. This approach is computationally efficient and scales well to different swarm sizes, to heterogeneous systems, and to both centralized and decentralized swarm models. Simulation results are presented for a swarm of 10 and 40 robots that follow circle, ellipse, and wedge formations. Experimental results are included to demonstrate the applicability of the approach on a swarm of four custom-built unmanned ground vehicles (UGVs). PMID:19447722

  7. Functional magnetic resonance imaging for defining the biological target volume

    PubMed Central

    Kauczor, Hans-Ulrich; Zechmann, Christian; Stieltjes, Bram; Weber, Marc-Andre

    2006-01-01

    Morphology as demonstrated by CT is the basis for radiotherapy planning. Intensity-modulated and adaptive radiotherapy techniques would greatly benefit from additional functional information allowing for definition of the biological target volume. MRI techniques include several which can characterize and quantify different tissue properties and their tumour-related changes. Results of perfusion MRI represent microvascular density and permeability; MR spectroscopy depicts particular metabolites; diffusion weighted imaging shows tissue at risk and tumour cellularity; while dynamic 3D acquisition (4D MRI) shows organ motion and the mobility of tumours within them. PMID:16766269

  8. Defining Genome Maintenance Pathways using Functional Genomic Approaches

    PubMed Central

    Bansbach, Carol E.; Cortez, David

    2011-01-01

    Genome maintenance activities including DNA repair, cell division cycle control, and checkpoint signaling pathways preserve genome integrity and prevent disease. Defects in these pathways cause birth defects, neurodegeneration, premature aging, and cancer. Recent technical advances in functional genomic approaches such as expression profiling, proteomics, and RNA interference (RNAi) technologies have rapidly expanded our knowledge of the proteins that work in these pathways. In this review, we examine the use of these high-throughput methodologies in higher eukaryotic organisms for the interrogation of genome maintenance activities. PMID:21787120

  9. Defining functional signatures of dysbiosis in periodontitis progression.

    PubMed

    Wang, Gary P

    2015-01-01

    Periodontitis is a common inflammatory disease that leads to tooth loss and has been linked to cardiovascular disease and diabetes mellitus. The periodontal microbiome is highly diverse, and metatranscriptomic studies have indicated that the genes that are expressed by the microbiota are more relevant than the microbial composition in the pathogenesis of periodontitis. A recent study of early metabolic activities in the dysbiotic microbiome reveals a functional signature that distinguishes periodontal sites that will become inflamed, supporting the idea that microbial communities as a whole drive disease progression. PMID:25926890

  10. Defining the neurocircuitry of borderline personality disorder: functional neuroimaging approaches.

    PubMed

    Brendel, Gary R; Stern, Emily; Silbersweig, David A

    2005-01-01

    Functional neuroimaging recently has been used to localize brain dysfunction in borderline personality disorder (BPD). Initial studies have examined baseline activity or emotional reactivity, and our group has investigated what we consider to be a crucial interaction between negative emotion and behavioral (dys)control. This research is beginning to identify abnormal frontolimbic circuitry likely underlying core clinical features of this condition. We review the evidence for dysfunction in specific frontolimbic regions, leading to a mechanistic model of symptom formation in BPD. In addition, we offer an integration of these neuroimaging findings with developmental perspectives on the emergence of borderline psychopathology, focusing on the ways in which early psychosocial experience may interact with developing brain systems. We also consider possible mechanisms of psychotherapeutic change at the neural systems level in BPD. Finally, we propose that future neuroimaging studies of BPD should integrate multiple levels of observation (structural, functional, neurochemical, genetic, and clinical) in a model-driven fashion to further understand the dynamic relationship between biological and psychological factors in the development and treatment of this difficult condition. PMID:16613437

  11. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

    PubMed Central

    Bidlingmaier, Scott; Zhu, Xiaodong; Liu, Bin

    2008-01-01

    Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is responsible for maintaining the growth of neoplastic tissue. The expression of the CD133 epitopes, AC133 and AC141, has been shown to define a subpopulation of brain tumor cells with significantly increased capacity for tumor initiation in xenograft models. Following the discovery of the AC133/AC141+ population of brain tumor stem cells, the AC133 and AC141 epitopes have been extensively used as markers for purifying CSCs in other solid tumors. There are, however, several issues associated with the use of the AC133 and AC141 CD133 epitopes as markers for CSCs. The antibodies routinely used for purification of AC133 and AC141-positive cells target poorly characterized glycosylated epitopes of uncertain specificity. Discordant expression of the AC133 and AC141 epitopes has been observed, and the epitopes can be absent despite the presence of CD133 protein. In addition, CD133 expression has recently been shown to be modulated by oxygen levels. These factors, in combination with the uncertain biological role of CD133, suggest that the use of CD133 expression as a marker for CSCs should be critically evaluated in each new experimental system and highlight the need for additional CSC surface markers that are directly involved in maintaining CSC properties. PMID:18535813

  12. 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

  13. 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. PMID:27374777

  14. Utility Green-Pricing Programs: What Defines Success? (Topical Issues Brief)

    SciTech Connect

    Swezey, B.; Bird, L.

    2001-09-13

    ''Green pricing'' is an optional service through which customers can support a greater level of investment by their electric utility in renewable energy technologies. Electric utilities in 29 states are now implementing green-pricing programs. This report examines important elements of green-pricing programs, including the different types of programs offered, the premiums charged, customer response, and additional factors that experience indicates are key to the development of successful programs. The best-performing programs tend to share a number of common attributes related to product design, value creation, product pricing, and program implementation. The report ends with a list of ''best practices'' for utilities to follow when developing and implementing programs.

  15. 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...

  16. 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…

  17. 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

  18. 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

  19. Diversity of Pol IV Function Is Defined by Mutations at the Maize rmr7 Locus

    PubMed Central

    Erhard, Karl F.; Hollick, Jay B.

    2009-01-01

    Mutations affecting the heritable maintenance of epigenetic states in maize identify multiple small RNA biogenesis factors including NRPD1, the largest subunit of the presumed maize Pol IV holoenzyme. Here we show that mutations defining the required to maintain repression7 locus identify a second RNA polymerase subunit related to Arabidopsis NRPD2a, the sole second largest subunit shared between Arabidopsis Pol IV and Pol V. A phylogenetic analysis shows that, in contrast to representative eudicots, grasses have retained duplicate loci capable of producing functional NRPD2-like proteins, which is indicative of increased RNA polymerase diversity in grasses relative to eudicots. Together with comparisons of rmr7 mutant plant phenotypes and their effects on the maintenance of epigenetic states with parallel analyses of NRPD1 defects, our results imply that maize utilizes multiple functional NRPD2-like proteins. Despite the observation that RMR7/NRPD2, like NRPD1, is required for the accumulation of most siRNAs, our data indicate that different Pol IV isoforms play distinct roles in the maintenance of meiotically-heritable epigenetic information in the grasses. PMID:19936246

  20. 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…

  1. Chloromethane-Induced Genes Define a Third C1 Utilization Pathway in Methylobacterium chloromethanicum CM4

    PubMed Central

    Studer, Alex; McAnulla, Craig; Büchele, Rainer; Leisinger, Thomas; Vuilleumier, Stéphane

    2002-01-01

    Methylobacterium chloromethanicum CM4 is an aerobic α-proteobacterium capable of growth with chloromethane as the sole carbon and energy source. Two proteins, CmuA and CmuB, were previously purified and shown to catalyze the dehalogenation of chloromethane and the vitamin B12-mediated transfer of the methyl group of chloromethane to tetrahydrofolate. Three genes located near cmuA and cmuB, designated metF, folD and purU and encoding homologs of methylene tetrahydrofolate (methylene-H4folate) reductase, methylene-H4folate dehydrogenase-methenyl-H4folate cyclohydrolase and formyl-H4folate hydrolase, respectively, suggested the existence of a chloromethane-specific oxidation pathway from methyl-tetrahydrofolate to formate in strain CM4. Hybridization and PCR analysis indicated that these genes were absent in Methylobacterium extorquens AM1, which is unable to grow with chloromethane. Studies with transcriptional xylE fusions demonstrated the chloromethane-dependent expression of these genes. Transcriptional start sites were mapped by primer extension and allowed to define three transcriptional units, each likely comprising several genes, that were specifically expressed during growth of strain CM4 with chloromethane. The DNA sequences of the deduced promoters display a high degree of sequence conservation but differ from the Methylobacterium promoters described thus far. As shown previously for purU, inactivation of the metF gene resulted in a CM4 mutant unable to grow with chloromethane. Methylene-H4folate reductase activity was detected in a cell extract of strain CM4 only in the presence of chloromethane but not in the metF mutant. Taken together, these data provide evidence that M. chloromethanicum CM4 requires a specific set of tetrahydrofolate-dependent enzymes for growth with chloromethane. PMID:12057941

  2. 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…

  3. Exploring utility function in utility management: an evaluating method of library preservation.

    PubMed

    Yan, Bin; Shi, Feng; Yu, Rui-Qiang

    2013-12-01

    In order to seek a new method of book evaluation and realize book resources sharing among the regional university libraries, we think that library should collect books of the high utility value in the case of limited funds. We proposed a changing Bellman equation as a utility function and used the explicit functions of the book usage factor and the book usage half-life derived from the utility function as an evaluating method of the collecting books. The results from empirical data given some conclusions such as the varieties diversity, the collected risk, the tendencies of reading varieties, species continuity and so on and a librarian can use the utility management to supplement the collections management. PMID:23607083

  4. 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.

  5. 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

  6. [What do functionally defined populations contribute to the explanation of regional differences in medical care?].

    PubMed

    Graf von Stillfried, D; Czihal, T

    2014-02-01

    Geographic variation in health care is increasingly subject to analysis and health policy aiming at the suitable allocation of resources and the reduction of unwarranted variation for the patient populations concerned. As in the case of area-level indicators, in most cases populations are geographically defined. The concept of geographically defined populations, however, may be self-limiting with respect to identifying the potential for improvement. As an alternative, we explored how a functional definition of populations would support defining the scope for reducing unwarranted geographical variations. Given that patients in Germany have virtually no limits in accessing physicians of their choice, we adapted a method that has been developed in the United States to create virtual networks of physicians based on commonly treated patients. Using the physician claims data under statutory insurance, which covers 90% of the population, we defined 43,006 populations-and networks-in 2010. We found that there is considerable variation between the population in terms of their risk structure and the share of the primary care practice in the total services provided. Moreover, there are marked differences in the size and structure of networks between cities, densely populated regions, and rural regions. We analyzed the variation for two area-level indicators: the proportion of diabetics with at least one HbA1c test per year for diabetics, and the proportion of patients with low back pain undergoing computed tomography and/or magnetic resonance imaging. Variation at the level of functionally defined populations proved to be larger than for geographically defined populations. The pattern of distribution gives evidence on the degree to which consensus targets could be reached and which networks need to be addressed in order to reduce unwarranted regional variation. The concept of functionally defined populations needs to be further developed before implementation. PMID:24469283

  7. 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…

  8. 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…

  9. 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…

  10. Defining Functional Gene-Circuit Interfaces in the Mouse Nervous System

    PubMed Central

    Soden, Marta E.; Gore, Bryan B.; Zweifel, Larry S.

    2013-01-01

    Complexity in the nervous system is established by developmental genetic programs, maintained by differential genetic profiles, and sculpted by experiential and environmental influence over gene expression. Determining how specific genes define neuronal phenotypes, shape circuit connectivity, and regulate circuit function is essential for understanding how the brain processes information, directs behavior, and adapts to changing environments. Mouse genetics has contributed greatly to current percepts of gene-circuit interfaces in behavior, but considerable work remains. Large-scale initiatives to map gene expression and connectivity in the brain, together with advanced techniques in molecular genetics, now allow detailed exploration of the genetic basis of nervous system function at the level of specific circuit connections. In this review, we highlight several key advances for defining the function of specific genes within a neural network. PMID:24007626

  11. 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. PMID:23902311

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Loss-of-function analyses defines vital and redundant functions of the Plasmodium rhomboid protease family.

    PubMed

    Lin, Jing-Wen; Meireles, Patrícia; Prudêncio, Miguel; Engelmann, Sabine; Annoura, Takeshi; Sajid, Mohammed; Chevalley-Maurel, Séverine; Ramesar, Jai; Nahar, Carolin; Avramut, Cristina M C; Koster, Abraham J; Matuschewski, Kai; Waters, Andrew P; Janse, Chris J; Mair, Gunnar R; Khan, Shahid M

    2013-04-01

    Rhomboid-like proteases cleave membrane-anchored proteins within their transmembrane domains. In apicomplexan parasites substrates include molecules that function in parasite motility and host cell invasion. While two Plasmodium rhomboids, ROM1 and ROM4, have been examined, the roles of the remaining six rhomboids during the malaria parasite's life cycle are unknown. We present systematic gene deletion analyses of all eight Plasmodium rhomboid-like proteins as a means to discover stage-specific phenotypes and potential functions in the rodent malaria model, P. berghei. Four rhomboids (ROM4, 6, 7 and 8) are refractory to gene deletion, suggesting an essential role during asexual blood stage development. In contrast ROM1, 3, 9 and 10 were dispensable for blood stage development and exhibited no, subtle or severe defects in mosquito or liver development. Parasites lacking ROM9 and ROM10 showed no major phenotypic defects. Parasites lacking ROM1 presented a delay in blood stage patency following liver infection, but in contrast to a previous study blood stage parasites had similar growth and virulence characteristics as wild type parasites. Parasites lacking ROM3 in mosquitoes readily established oocysts but failed to produce sporozoites. ROM3 is the first apicomplexan rhomboid identified to play a vital role in sporogony. PMID:23490234

  17. 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

  18. Assessing the utility of a demand assessment for functional analysis.

    PubMed

    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 compliance or high levels of problem behavior (low-probability demands) and demands associated with high levels of compliance or low levels of problem behavior (high-probability demands). Results showed that clearer functional analysis outcomes were obtained for 3 of the 4 participants when low-probability rather than high-probability demands were used. PMID:20514188

  19. Direct Conversion of Fibroblasts into Functional Astrocytes by Defined Transcription Factors

    PubMed Central

    Caiazzo, Massimiliano; Giannelli, Serena; Valente, Pierluigi; Lignani, Gabriele; Carissimo, Annamaria; Sessa, Alessandro; Colasante, Gaia; Bartolomeo, Rosa; Massimino, Luca; Ferroni, Stefano; Settembre, Carmine; Benfenati, Fabio; Broccoli, Vania

    2014-01-01

    Summary Direct cell reprogramming enables direct conversion of fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell-lineage-specific transcription factors. This approach is rapid and simple, generating the cell types of interest in one step. However, it remains unknown whether this technology can be applied to convert fibroblasts into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis, and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB, and SOX9 to be sufficient to convert with high efficiency embryonic and postnatal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene-expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications. PMID:25556566

  20. Software defined radio based multi-carrier multi-function waveform for cognitive radio

    NASA Astrophysics Data System (ADS)

    Zhou, Ruolin; Li, Xue; Chakravarthy, Vasu; Wu, Zhiqiang

    2010-04-01

    In this paper, we demonstrate an adaptive multicarrier multi-function waveform generator for cognitive radio via software defined radio. Using a USRP (universal software radio peripheral) software defined radio boards and GNU radio software, we implement a multi-carrier waveform generator which can generate multi-function waveforms such as OFDM, NC-OFDM, MC-CDMA, NC-MC-CDMA, CI/MC-CDMA, NCCI/ MC-CDMA, TDCS for cognitive radio. Additionally, we demonstrate a portable overlay cognitive radio using this multicarrier multi-function waveform generator. This cognitive radio is capable of detecting primary users in real time and adaptively adjusting its transmission parameters to avoid interference to primary users. More importantly, this cognitive radio can take advantage of multiple spectrum holes by employing non-contiguous multi-carrier transmission technologies. Additionally, we demonstrate that when the primary user transmission changes, the cognitive radio dynamically adjusts its transmission accordingly. We also demonstrate seamless real time video transmission between two cognitive radio nodes, while avoiding interference from primary users and interference to primary users operating in the same spectrum.

  1. 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

  2. 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

  3. 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

  4. An algorithmic method for functionally defining regions of interest in the ventral visual pathway.

    PubMed

    Julian, J B; Fedorenko, Evelina; Webster, Jason; Kanwisher, Nancy

    2012-05-01

    In a widely used functional magnetic resonance imaging (fMRI) data analysis method, functional regions of interest (fROIs) are handpicked in each participant using macroanatomic landmarks as guides, and the response of these regions to new conditions is then measured. A key limitation of this standard handpicked fROI method is the subjectivity of decisions about which clusters of activated voxels should be treated as the particular fROI in question in each subject. Here we apply the Group-Constrained Subject-Specific (GSS) method for defining fROIs, recently developed for identifying language fROIs (Fedorenko et al., 2010), to algorithmically identify fourteen well-studied category-selective regions of the ventral visual pathway (Kanwisher, 2010). We show that this method retains the benefit of defining fROIs in individual subjects without the subjectivity inherent in the traditional handpicked fROI approach. The tools necessary for using this method are available on our website (http://web.mit.edu/bcs/nklab/GSS.shtml). PMID:22398396

  5. Changes in everyday function among individuals with psychometrically defined Mild Cognitive Impairment in the ACTIVE Study

    PubMed Central

    Wadley, Virginia G.; Crowe, Michael; Marsiske, Michael; Cook, Sarah E.; Unverzagt, Frederick W.; Rosenberg, Adrienne L.; Rexroth, Daniel

    2007-01-01

    Objectives. Because many individuals with Mild Cognitive Impairment (MCI) will progress to a dementia diagnosis, this population is at high risk for losing functional independence. We examine trajectories of change in everyday function for individuals with cognitive deficits suggestive of MCI. Design. We utilized data from the longitudinal, multi-site Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, which allowed for post-hoc classification of MCI status at baseline using psycho metric definitions for amnestic MCI, non-amnestic MCI, multi-domain MCI, and no MCI. Setting. Six U.S. cities. Participants. 2832 volunteers (mean age 74 years; 26% African American) living independently, recruited from senior housing, community centers, and hospitals and clinics. Measurements. Mixed effect models examined changes in self-reported instrumental and basic activities of daily living (IADLs and ADLs) from the MDS Home Care Interview in 2,358 participants over a three-year period. Results. In models for IADL performance, IADL difficulty, and a Daily Functioning Composite, there was a significant time by MCI classification interaction for each MCI subtype, indicating that all MCI groups showed faster rates of decline in everyday function relative to cognitively normal participants with no MCI. Conclusion. Results demonstrate the importance of MCI as a clinical entity that not only predicts progression to dementia but also predicts functional declines in activities that are key to autonomy and quality of life. MCI classification guidelines should allow for functional changes in MCI, and clinicians should monitor for such changes. Preservation of function may serve as a meaningful outcome for intervention efforts. PMID:17661957

  6. The Richness of Task-Evoked Hemodynamic Responses Defines a Pseudohierarchy of Functionally Meaningful Brain Networks.

    PubMed

    Orban, Pierre; Doyon, Julien; Petrides, Michael; Mennes, Maarten; Hoge, Richard; Bellec, Pierre

    2015-09-01

    Functional magnetic resonance imaging can measure distributed and subtle variations in brain responses associated with task performance. However, it is unclear whether the rich variety of responses observed across the brain is functionally meaningful and consistent across individuals. Here, we used a multivariate clustering approach that grouped brain regions into clusters based on the similarity of their task-evoked temporal responses at the individual level, and then established the spatial consistency of these individual clusters at the group level. We observed a stable pseudohierarchy of task-evoked networks in the context of a delayed sequential motor task, where the fractionation of networks was driven by a gradient of involvement in motor sequence preparation versus execution. In line with theories about higher-level cognitive functioning, this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition, parcellations in the cerebellum and basal ganglia matched with known anatomical territories and fiber pathways with the cerebral cortex. These findings demonstrate that subtle variations in brain responses associated with task performance are systematic enough across subjects to define a pseudohierarchy of task-evoked networks. Such networks capture meaningful functional features of brain organization as shaped by a given cognitive context. PMID:24729172

  7. Defining recovery from an eating disorder: Conceptualization, validation, and examination of psychosocial functioning and psychiatric comorbidity.

    PubMed

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

    2010-03-01

    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

  8. 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

  9. 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.

  10. 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

  11. Possible role of ceramide in defining structure and function of membrane glycolipids.

    PubMed Central

    Kannagi, R; Nudelman, E; Hakomori, S

    1982-01-01

    A possible role of ceramide in defining the carbohydrate structure of glycolipids and the expression of glycolipid function has been proposed, on the basis of our finding that the ceramide composition of "lacto-series" glycosphingolipid isolated from human erythrocytes shows a remarkable correlation with the terminal carbohydrate structure: (i) The ceramides of three glycosphingolipids with Lex (or x) determinant [Gal beta 1 leads to 4(Fuc alpha 1 leads to 3) GlcNAc] had almost exclusively 16:0 fatty acid; in contrast, the ceramide of its positional isomer H determinant had mainly 20--24:0 fatty acids. (ii) The ceramide of two glycosphingolipids with NeuAc alpha 2 leads to 6GAL structure was predominantly of 16:0 fatty acid, in contrast to that of its positional isomer NeuAc alpha 2 leads to 3Gal residue, in which the ceramide had 20--24:0 fatty acids. These results, together with our previous observation that ceramide composition of mouse lymphoma and myelocytic leukemia MI cells affects their antigenicity, suggest that ceramide structure may define the organization of glycosyltransferase for synthesis of the carbohydrate determinants and may affect the organization and orientation of the carbohydrate chain in membranes, eliciting or suppressing the reactivity to its ligand. Because these glycolipids with Lex and NeuAc alpha 2 leads to 6Gal structures are developmentally regulated and are highly expressed in certain tumors, ceramide composition may affect development, differentiation, and oncogenesis. Images PMID:6954491

  12. 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. PMID:22292616

  13. Genetic lineage tracing defines myofibroblast origin and function in the injured heart.

    PubMed

    Kanisicak, Onur; Khalil, Hadi; Ivey, Malina J; Karch, Jason; Maliken, Bryan D; Correll, Robert N; Brody, Matthew J; J Lin, Suh-Chin; Aronow, Bruce J; Tallquist, Michelle D; Molkentin, Jeffery D

    2016-01-01

    Cardiac fibroblasts convert to myofibroblasts with injury to mediate healing after acute myocardial infarction (MI) and to mediate long-standing fibrosis with chronic disease. Myofibroblasts remain a poorly defined cell type in terms of their origins and functional effects in vivo. Here we generate Postn (periostin) gene-targeted mice containing a tamoxifen-inducible Cre for cellular lineage-tracing analysis. This Postn allele identifies essentially all myofibroblasts within the heart and multiple other tissues. Lineage tracing with four additional Cre-expressing mouse lines shows that periostin-expressing myofibroblasts in the heart derive from tissue-resident fibroblasts of the Tcf21 lineage, but not endothelial, immune/myeloid or smooth muscle cells. Deletion of periostin(+) myofibroblasts reduces collagen production and scar formation after MI. Periostin-traced myofibroblasts also revert back to a less-activated state upon injury resolution. Our results define the myofibroblast as a periostin-expressing cell type necessary for adaptive healing and fibrosis in the heart, which arises from Tcf21(+) tissue-resident fibroblasts. PMID:27447449

  14. 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

  15. FPGA-Based Reconfigurable Measurement Instruments with Functionality Defined by User

    NASA Astrophysics Data System (ADS)

    Tsai, Guo-Ruey; Lin, Min-Chuan

    2006-12-01

    Using the field-programmable gate array (FPGA) with embedded software-core processor and/or digital signal processor cores, we are able to construct a hardware kernel for measurement instruments, which can fit common electronic measurement and test requirements. We call this approach the software-defined instrumentation (SDI). By properly configuring, we have used the hardware kernel to implement an[InlineEquation not available: see fulltext.]-channel arbitrary waveform generator with various add-on functions, a wideband and precise network analyzer, a high-speed signal digitizer, and a real-time sweep spectrum analyzer. With adaptively reconfiguring the hardware kernel, SDI concept can easily respond to the rapidly changing user-application-specified needs in measurement and test markets.

  16. 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

  17. A Constrained Genetic Algorithm with Adaptively Defined Fitness Function in MRS Quantification

    NASA Astrophysics Data System (ADS)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; Graveron-Demilly, D.; van Ormondt, D.

    MRS Signal quantification is a rather involved procedure and has attracted the interest of the medical engineering community, regarding the development of computationally efficient methodologies. Significant contributions based on Computational Intelligence tools, such as Neural Networks (NNs), demonstrated a good performance but not without drawbacks already discussed by the authors. On the other hand preliminary application of Genetic Algorithms (GA) has already been reported in the literature by the authors regarding the peak detection problem encountered in MRS quantification using the Voigt line shape model. This paper investigates a novel constrained genetic algorithm involving a generic and adaptively defined fitness function which extends the simple genetic algorithm methodology in case of noisy signals. The applicability of this new algorithm is scrutinized through experimentation in artificial MRS signals interleaved with noise, regarding its signal fitting capabilities. Although extensive experiments with real world MRS signals are necessary, the herein shown performance illustrates the method's potential to be established as a generic MRS metabolites quantification procedure.

  18. 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,…

  19. 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…

  20. Functional differences between neurochemically defined populations of inhibitory interneurons in the rat spinal dorsal horn☆

    PubMed Central

    Polgár, Erika; Sardella, Thomas C.P.; Tiong, Sheena Y.X.; Locke, Samantha; Watanabe, Masahiko; Todd, Andrew J.

    2013-01-01

    In order to understand how nociceptive information is processed in the spinal dorsal horn we need to unravel the complex synaptic circuits involving interneurons, which constitute the vast majority of the neurons in laminae I–III. The main limitation has been the difficulty in defining functional populations among these cells. We have recently identified 4 non-overlapping classes of inhibitory interneuron, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) and parvalbumin, in the rat spinal cord. In this study we demonstrate that these form distinct functional populations that differ in terms of sst2A receptor expression and in their responses to painful stimulation. The sst2A receptor was expressed by nearly all of the nNOS- and galanin-containing inhibitory interneurons but by few of those with NPY and none of the parvalbumin cells. Many galanin- and NPY-containing cells exhibited phosphorylated extracellular signal-regulated kinases (pERK) after mechanical, thermal or chemical noxious stimuli, but very few nNOS-containing cells expressed pERK after any of these stimuli. However, many nNOS-positive inhibitory interneurons up-regulated Fos after noxious thermal stimulation or injection of formalin, but not after capsaicin injection. Parvalbumin cells did not express either activity-dependent marker following any of these stimuli. These results suggest that interneurons belonging to the NPY, nNOS and galanin populations are involved in attenuating pain, and for NPY and nNOS cells this is likely to result from direct inhibition of nociceptive projection neurons. They also suggest that the nociceptive inputs to the nNOS cells differ from those to the galanin and NPY populations. PMID:23707280

  1. Empirically Defined Patterns of Executive Function Deficits in Schizophrenia and Their Relation to Everyday Functioning: A Person-Centered Approach

    PubMed Central

    Iampietro, Mary; Giovannetti, Tania; Drabick, Deborah A. G.; Kessler, Rachel K.

    2013-01-01

    Executive function (EF) deficits in schizophrenia (SZ) are well documented, although much less is known about patterns of EF deficits and their association to differential impairments in everyday functioning. The present study empirically defined SZ groups based on measures of various EF abilities and then compared these EF groups on everyday action errors. Participants (n=45) completed various subtests from the Delis–Kaplan Executive Function System (D-KEFS) and the Naturalistic Action Test (NAT), a performance-based measure of everyday action that yields scores reflecting total errors and a range of different error types (e.g., omission, perseveration). Results of a latent class analysis revealed three distinct EF groups, characterized by (a) multiple EF deficits, (b) relatively spared EF, and (c) perseverative responding. Follow-up analyses revealed that the classes differed significantly on NAT total errors, total commission errors, and total perseveration errors; the two classes with EF impairment performed comparably on the NAT but performed worse than the class with relatively spared EF. In sum, people with SZ demonstrate variable patterns of EF deficits, and distinct aspects of these EF deficit patterns (i.e., poor mental control abilities) may be associated with everyday functioning capabilities. PMID:23035705

  2. 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

  3. Propagation of mouse and human T cells with defined antigen specificity and function.

    PubMed

    Cohen, P A; Fowler, D H; Kim, H; White, R L; Czerniecki, B J; Carter, C; Gress, R E; Rosenberg, S A

    1994-01-01

    Difficulties maintaining fully functional CD4+ T cells in culture have historically limited the study of their role in tumour rejection as well as other clinical applications. As the therapeutic value of current antitumour CD8+ T cell adoptive therapy becomes better defined, a strong impetus exists to determine optimal conditions for culturing antitumour CD4+ T cells. Our goal is to promote broadly polyclonal, antigen-specific CD4+ T cell responses of either Th1 or Th2 character for use in antitumour therapy or allograft facilitation, respectively. Similar obstacles exist in murine and human cultures: (1) during even brief periods of culture CD4+ T cells develop high 'background' reactivity to class II-positive antigen-presenting cells; (2) maintenance of antigen specificity as evidenced by cytokine secretion and short-term proliferation assays is insufficient to ensure bulk numerical expansion; (3) Th1-type CD4+ T cells often lose their potential for antigen-specific secretion of interleukin 2 on re-stimulation (though remain inducible by 12-O-tetradecanoylphorbol 13-acetate/ionomycin); (4) during prolonged culture selection pressure favours CD4+ subpopulations that recognize artifactual antigens such as culture medium proteins; (5) even with optimal culture conditions, cultured CD4+ T cells may function differently in vivo to uncultured CD4+ T cells. We have devised various strategies to surmount these obstacles by use of selected cytokines, antigen-presenting cells and timely culture manoeuvres. PMID:7540969

  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.

    PubMed

    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

  6. 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.

  7. Defining Staff Roles and Responsibilities with Integration: A Model for Effective Utilization of Special Education Staff in the Regular Classroom.

    ERIC Educational Resources Information Center

    Gallagher, Vicky A.

    This practicum report addressed the problem of role ambiguity in regard to effective utilization of special education staff within the regular fourth grade classroom and the need for support for the regular teacher working with special education students. The researcher, a special educator, conducted the following activities: (1) presented an…

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

    PubMed

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

    2016-06-01

    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 machinery with

  9. 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

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

    PubMed Central

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    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. PMID:23804499

  11. A regulon conserved in monocot and dicot plants defines a functional module in antifungal plant immunity

    PubMed Central

    Humphry, Matt; Bednarek, Paweł; Kemmerling, Birgit; Koh, Serry; Stein, Mónica; Göbel, Ulrike; Stüber, Kurt; Piślewska-Bednarek, Mariola; Loraine, Ann; Schulze-Lefert, Paul; Somerville, Shauna; Panstruga, Ralph

    2010-01-01

    At least two components that modulate plant resistance against the fungal powdery mildew disease are ancient and have been conserved since the time of the monocot–dicot split (≈200 Mya). These components are the seven transmembrane domain containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act antagonistically and have been identified in the monocot barley (Hordeum vulgare) and the dicot Arabidopsis thaliana, respectively. Additionally, syntaxin-interacting N-ethylmaleimide sensitive factor adaptor protein receptor proteins (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis. Here, we show that these genetically defined defense components share a similar set of coexpressed genes in the two plant species, comprising a statistically significant overrepresentation of gene products involved in regulation of transcription, posttranslational modification, and signaling. Most of the coexpressed Arabidopsis genes possess a common cis-regulatory element that may dictate their coordinated expression. We exploited gene coexpression to uncover numerous components in Arabidopsis involved in antifungal defense. Together, our data provide evidence for an evolutionarily conserved regulon composed of core components and clade/species-specific innovations that functions as a module in plant innate immunity. PMID:21098265

  12. Spatially invariant coding of numerical information in functionally defined subregions of human parietal cortex.

    PubMed

    Eger, E; Pinel, P; Dehaene, S; Kleinschmidt, A

    2015-05-01

    Macaque electrophysiology has revealed neurons responsive to number in lateral (LIP) and ventral (VIP) intraparietal areas. Recently, fMRI pattern recognition revealed information discriminative of individual numbers in human parietal cortex but without precisely localizing the relevant sites or testing for subregions with different response profiles. Here, we defined the human functional equivalents of LIP (feLIP) and VIP (feVIP) using neurophysiologically motivated localizers. We applied multivariate pattern recognition to investigate whether both regions represent numerical information and whether number codes are position specific or invariant. In a delayed number comparison paradigm with laterally presented numerosities, parietal cortex discriminated between numerosities better than early visual cortex, and discrimination generalized across hemifields in parietal, but not early visual cortex. Activation patterns in the 2 parietal regions of interest did not differ in the coding of position-specific or position-independent number information, but in the expression of a numerical distance effect which was more pronounced in feLIP. Thus, the representation of number in parietal cortex is at least partially position invariant. Both feLIP and feVIP contain information about individual numerosities in humans, but feLIP hosts a coarser representation of numerosity than feVIP, compatible with either broader tuning or a summation code. PMID:24293562

  13. 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.

  14. Effects function analysis of ELF magnetic field exposure in the electric utility work environment.

    PubMed

    Zhang, J; Nair, I; Sahl, J

    1997-01-01

    The incomplete understanding of the relation between power-frequency fields and biological responses raises problems in defining an appropriate metric for exposure assessment and epidemiological studies. Based on evidence from biological experiments, one can define alternative metrics or effects functions that embody the relationship between field exposure patterns and hypothetical health effects. In this paper, we explore the application of the "effects function" approach to occupational exposure data. Our analysis provides examples of exposure assessments based on a range of plausible effects functions. An EMDEX time series data set of ELF frequency (40-800 Hz) magnetic field exposure measurements for electric utility workers was analyzed with several statistical measures and effects functions: average field strength, combination of threshold and exposure duration, and field strength changes. Results were compared for eight job categories: electrician, substation operator, machinist, welder, plant operator, lineman/splicer, meter reader, and clerical. Average field strength yields a different ranking for these job categories than the ranks obtained using other biologically plausible effects functions. Whereas the group of electricians has the highest exposure by average field strength, the group of substation operators has the highest ranking for most of the other effects functions. Plant operators rank highest in the total number of field strength changes greater than 1 microT per hour. The clerical group remains at the lowest end for all of these effects functions. Our analysis suggests that, although average field strength could be used as a surrogate of field exposure for simply classifying exposure into "low" and "high," this summary measure may be misleading in the relative ranking of job categories in which workers are in "high" fields. These results indicate the relevance of metrics other than average field strength in occupational exposure assessment and

  15. Gross Motor Function Classification System: impact and utility.

    PubMed

    Morris, Christopher; Bartlett, Doreen

    2004-01-01

    In summary, the GMFCS has had, and continues to have, a major effect on the health care of children with CP. The number of citations of the GMFCS has been increasing every year, and the classification system has had good uptake internationally and across the spectrum of health professionals for use in research design and clinical practice by providing a system for clearly communicating about children's gross motor function. The utility of diagnostic labels such as diplegia has been questioned. However, although by definition CP is a disorder of posture and movement, the movement disability is often only one of the neurodevelopmental problems for many children with CP. When a complete description of a child's clinical presentation is required we recommend that the GMFCS be used together with the Surveillance of Cerebral Palsy in Europe classification indicating the type and topography of movement impairment. When appropriate the clinical profile will similarly be enhanced with details of other impairments and disabilities such as epilepsy or sensory, learning, feeding, or emotional disturbance. The observations in this annotation are constrained by the amount of information in the public domain. Although these sources adequately represent the effect of the GMFCS on research design, they are less likely to inform us of how the GMFCS is being used in administration, clinical practice, or education. It is not yet clear whether information is being used for these purposes or in assisting with case load management, as intended by the developers. By its localized nature, such information might remain difficult to gauge. We would therefore be interested to hear from others who are using the system for these or any other purposes. PMID:14974650

  16. 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.

  17. Pulling the [open quotes]reverse trigger[close quotes]: A way to define local competition. [Competition among Public Utilities

    SciTech Connect

    Barnich, T.L.; Clausen, C.L.

    1994-06-15

    The communications convergence, brought about largely by the digitalization revolution, is now moving in a double helix through the horizontal telecommunications hierarchy. Competition for customer premises is aspiring upward toward the competition that is spiraling downward from the long-distance market. The competitive-access market is growing rapidly. MCI Metro, MCI/Nextel, and AT T/McCaw are poised to reach down into the traditionally [open quotes]local[close quotes] markets through wires and airwaves alike. Even the electric utilities are building persuasive business cases and regulatory arguments to transform their erstwhile internal communications systems, conduits, and rights-of-way into commercial networks offering cable TV, multimedia, Personal Communications Service (PCS), and alternative telephony services. The four principles in developing a regulatory standard should be: create standards that ease regulatory babysitting, recognize the relationship between the costs of regulatory compliance and building the networks, minimize transaction costs, and let the networks begin to grow now, without time and energy being spent on gaming the regulatory system.

  18. 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.

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

    DOE PAGESBeta

    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

  20. 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

  1. 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

  2. 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

  3. 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

  4. Functional studies on Calliphora vomitoria haemocyte subpopulations defined by lectin staining and density centrifugation.

    PubMed

    McKenzie, A N; Preston, T M

    1992-01-01

    Haemocyte subpopulations of Calliphora vomitoria have been categorized by their surface staining properties using fluorescently labelled lectins, and their mobilities in Percoll density gradients. These methods of identification were exploited to determine the roles of these cell types in cellular defence reactions. Soybean agglutinin clearly defined the cell subpopulation involved in phagocytosis, while purified thrombocytoid fragments proved to be the main haemocyte population involved in encapsulation and nodule formation. PMID:1377650

  5. 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

  6. A Method of Defining "Packages" of Maternal Stimulation and Their Functional Significance for the Infant with Mother and Stranger.

    ERIC Educational Resources Information Center

    Beebe, Beatrice; Gerstman, Louis

    1984-01-01

    Presents a method of defining cooccurring constellations or "packages" of maternal facial-visual engagement and head or hand stimulation during face-to-face play with an infant. The functional relevance of these packages is documented in case studies of one four-month-old infant playing with his mother and a stranger. (Author/CB)

  7. 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...

  8. Performance evaluation of multi-stratum resources integration based on network function virtualization in software defined elastic data center optical interconnect.

    PubMed

    Yang, Hui; Zhang, Jie; Ji, Yuefeng; Tian, Rui; Han, Jianrui; Lee, Young

    2015-11-30

    Data center interconnect with elastic optical network is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented multi-stratum resilience between IP and elastic optical networks that allows to accommodate data center services. In view of this, this study extends to consider the resource integration by breaking the limit of network device, which can enhance the resource utilization. We propose a novel multi-stratum resources integration (MSRI) architecture based on network function virtualization in software defined elastic data center optical interconnect. A resource integrated mapping (RIM) scheme for MSRI is introduced in the proposed architecture. The MSRI can accommodate the data center services with resources integration when the single function or resource is relatively scarce to provision the services, and enhance globally integrated optimization of optical network and application resources. The overall feasibility and efficiency of the proposed architecture are experimentally verified on the control plane of OpenFlow-based enhanced software defined networking (eSDN) testbed. The performance of RIM scheme under heavy traffic load scenario is also quantitatively evaluated based on MSRI architecture in terms of path blocking probability, provisioning latency and resource utilization, compared with other provisioning schemes. PMID:26698748

  9. Effectiveness of interruptive alerts in increasing application functionality utilization: a controlled trial.

    PubMed

    Turchin, Alexander; James, Oliver D; Godlewski, Eric D; Shubina, Maria; Coley, Christopher M; Gandhi, Tejal K; Broverman, Carol

    2011-06-01

    Medical applications frequently contain a wide range of functionalities. Users are often unaware of all of the functionalities available. More effective ways of delivering information about available functionalities to the users are needed. We conducted a pseudo-randomized controlled trial to determine whether interruptive alerts will increase utilization of several functionalities by the users of the Pre-Admission Medication List (PAML) Builder application at two academic medical centers. In a log-linear model, alerts increased total utilization of the promoted functionalities per PAML built by 70% compared to the controls at the site level (p<0.0001). At the user level, frequency of utilization of the PAML Builder functionalities by individual users increased by 0.03 for every extra alert shown to the user (p<0.0001). Alerts led to a nearly 2-fold increase in utilization of the promoted functionalities. Interruptive alerts are an effective method of delivering information about application functionalities to users. PMID:20637899

  10. Scaling of topologically similar functional modules defines mouse primary auditory and somatosensory microcircuitry.

    PubMed

    Sadovsky, Alexander J; MacLean, Jason N

    2013-08-28

    Mapping the flow of activity through neocortical microcircuits provides key insights into the underlying circuit architecture. Using a comparative analysis we determined the extent to which the dynamics of microcircuits in mouse primary somatosensory barrel field (S1BF) and auditory (A1) neocortex generalize. We imaged the simultaneous dynamics of up to 1126 neurons spanning multiple columns and layers using high-speed multiphoton imaging. The temporal progression and reliability of reactivation of circuit events in both regions suggested common underlying cortical design features. We used circuit activity flow to generate functional connectivity maps, or graphs, to test the microcircuit hypothesis within a functional framework. S1BF and A1 present a useful test of the postulate as both regions map sensory input anatomically, but each area appears organized according to different design principles. We projected the functional topologies into anatomical space and found benchmarks of organization that had been previously described using physiology and anatomical methods, consistent with a close mapping between anatomy and functional dynamics. By comparing graphs representing activity flow we found that each region is similarly organized as highlighted by hallmarks of small world, scale free, and hierarchical modular topologies. Models of prototypical functional circuits from each area of cortex were sufficient to recapitulate experimentally observed circuit activity. Convergence to common behavior by these models was accomplished using preferential attachment to scale from an auditory up to a somatosensory circuit. These functional data imply that the microcircuit hypothesis be framed as scalable principles of neocortical circuit design. PMID:23986241

  11. 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

  12. 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

  13. The Role of the Functionality Rule in the Categorization of Well-Defined Concepts.

    ERIC Educational Resources Information Center

    Richards, D. Dean; And Others

    1989-01-01

    Findings of two experiments support the contention that children and adults are capable of using both hypothetical counter-exemplar reasoning and functionality to make definitional category judgments. Results are discussed in terms of Richards and Goldfarb's (1986) model of episodic memory and are related to other evidence that children possess…

  14. Functionally associated targets in mantle cell lymphoma as defined by DNA microarrays and RNA interference.

    PubMed

    Ortega-Paino, Eva; Fransson, Johan; Ek, Sara; Borrebaeck, Carl A K

    2008-02-01

    Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with poor prognosis. Its hallmark is the translocation t(11:14)q (13;32), leading to overexpression of cyclin D1, a positive regulator of the cell cycle. As cyclin D1 up-regulation is not sufficient for inducing malignant transformation, we combined DNA microarray and RNA interference (RNAi) approaches to identify novel deregulated genes involved in the progression of MCL. DNA microarray analysis identified 46 genes specifically up-regulated in MCL compared with normal B cells; 20 of these were chosen for further studies based on their cellular functions, such as growth and proliferation. The Granta 519 cell line was selected as an MCL in vitro model, to set up the RNAi protocol. To confirm the functionality of overexpression of the 20 disease-associated genes, they were knocked down using small interfering RNAs (siRNAs). In particular, knockdown of 3 genes, encoding the hepatoma-derived growth factor related protein 3 (HDGFRP3), the frizzled homolog 2 (FZD2), and the dual specificity phosphatase 5 (DUSP5), induced proliferative arrest in Granta 519 MCL cells. These genes emerged as functionally associated in MCL, in relation to growth and survival, and interfering with their function would increase insight into lymphoma growth regulation, potentially leading to novel clinical intervention modalities. PMID:18024791

  15. 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

  16. 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

  17. Structural Waters Define a Functional Channel Mediating Activation of the GPCR, rhodopsin

    SciTech Connect

    Angel, T.; Gupta, S; Jastrzebska, B; Palczewski, K; Chance, M

    2009-01-01

    Structural water molecules may act as prosthetic groups indispensable for proper protein function. In the case of allosteric activation of G protein-coupled receptors (GPCRs), water likely imparts structural plasticity required for agonist-induced signal transmission. Inspection of structures of GPCR superfamily members reveals the presence of conserved embedded water molecules likely important to GPCR function. Coupling radiolytic hydroxyl radical labeling with rapid H2O18 solvent mixing, we observed no exchange of these structural waters with bulk solvent in either ground state or for the Meta II or opsin states. However, the radiolysis approach permitted labeling of selected side chain residues within the transmembrane helices and revealed activation-induced changes in local structural constraints likely mediated by dynamics of both water and protein. These results suggest both a possible general mechanism for water-dependent communication in family A GPCRs based on structural conservation, and a strategy for probing membrane protein structure.

  18. 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

  19. 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

  20. 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

  1. Estimating Moho depth utilizing S-wave receiver functions

    NASA Astrophysics Data System (ADS)

    Ceylan, S.; Rychert, C.; Harmon, N.

    2014-12-01

    H-k stacking method [Zhu and Kanamori, 2000] is a widely used grid search technique for estimating the Moho depth (H) and Vp/Vs (k) beneath a given station. The H-k surface reaches a maximum when the optimum H and k values are used, which is assumed to be the average crustal structure beneath the seismic station. In general, the method is employed in conjunction with P-wave receiver functions. Here, we investigate the usability of H-k stacking method with S-to-P (Sp) conversions and S-wave reverberations within the crust, employing an extended multi-taper deconvolution. We apply the method to southern California, using data recorded between 1990-2011. We compare results with those of prior studies that used P-to-S (Ps) conversions [Zhu and Kanamori, 2000; Yan and Clayton, 2007], applying a smoothing length of 0.5 degrees to reflect lateral Sp sensitivity. P-waves have better potential to resolve lateral variations in Moho depth owing to the higher frequency content and the geometry of Ps ray path. Our results from Sp conversions are in broad agreement with those from Ps, affirming that S-wave receiver functions can be used in conjunction with the H-k stacking method. Consistent with the P-wave receiver function results, crust is thinner beneath the central Transverse Range (30 km) with respect to eastern Transverse Range (33 km) and Peninsular Region (35 km). Our Moho depth observations (35 km) are more compatible with those of Yan and Clayton [2007] (~35 km) than Zhu and Kanamori [2000] (~30 km) beneath Sierra Nevada, most probably due to a larger data set this study and Yan and Clayton [2007] use. Also, results from this study are deeper than those from Ps for the Salton Trough (30-35 km vs. 25 km). In this case, broad receiver function waveform characteristics suggest a more gradual impedance change across the Moho discontinuity and/or a multi-layered crust. We suggest that a combination of P- and S-wave receiver functions can yield more robust crustal thickness

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

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

    PubMed Central

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

    2015-01-01

    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 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. PMID:18661501

  9. 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

  10. Defining the functional domains in the control region of the adenovirus type 2 specific VARNA1 gene.

    PubMed

    Wu, G J; Railey, J F; Cannon, R E

    1987-04-01

    The outer boundaries of the internal transcriptional control region in the VARNA1 gene have been located from positions +10 to +69. To further define the detailed organization of the functional domains in this region and the function(s) of the 5' flanking sequence, and to obtain a more detailed insight into other transcriptionally important sequences, we have constructed 77 mutants with deletion endpoints at almost every one to five base-pairs in the entire region from -30 to +160 for transcriptional studies. Using our highly active crude extract under our assay conditions, and quantitatively measuring the transcriptional efficiency and competing strength of each mutant, we have revealed new features of important transcriptional control sequences and defined the transcriptional functions of several functional domains in this gene. The essential domain is from +59/+63 to +66/+68, which corresponds to the B block sequence. This is smaller than that defined previously. The second most important domain is the region from +12/14 to +40, which includes the A block sequence that dictates the wild-type major start site and amplifies the events started by the B block region, mediated through factors and RNA polymerase III. Furthermore, the domain from -5 to +11 affects the use of certain start site(s). Moreover, the 5' flanking region from -30 to +1 contributes 80 to 90% of the overall transcriptional efficiency of the gene. Finally, our transcriptional studies of mutants deleted of the A block sequence and all of the upstream sequence indicated that an intimate interaction between the two blocks is essential for initiation of transcription. Furthermore, the B block sequence is more important than the A block sequence in the transcription reaction. The mechanism and control of transcriptional initiation in the VARNA1 gene is similar to that in some tRNA genes, but differs from that in others. PMID:3625769

  11. CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages

    PubMed Central

    Fergusson, Joannah R.; Smith, Kira E.; Fleming, Vicki M.; Rajoriya, Neil; Newell, Evan W.; Simmons, Ruth; Marchi, Emanuele; Björkander, Sophia; Kang, Yu-Hoi; Swadling, Leo; Kurioka, Ayako; Sahgal, Natasha; Lockstone, Helen; Baban, Dilair; Freeman, Gordon J.; Sverremark-Ekström, Eva; Davis, Mark M.; Davenport, Miles P.; Venturi, Vanessa; Ussher, James E.; Willberg, Christian B.; Klenerman, Paul

    2014-01-01

    The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a novel population known as Mucosal Associated Invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, that can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Further, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161 expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both TCR expression and cell lineage. PMID:25437561

  12. 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

  13. 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

  14. The ECOMAN project: A novel approach to defining sustainable ecosystem function.

    PubMed

    Galloway, Tamara S; Brown, Rebecca J; Browne, Mark A; Dissanayake, Awantha; Lowe, David; Depledge, Michael H; Jones, Malcolm B

    2006-01-01

    The ECOMAN was initiated in 2001 by the University of Plymouth, UK, Plymouth Marine Laboratory and the Department of the Environment, Fisheries and Rural Affairs (DEFRA) to address the need for more pragmatic assessment techniques linking environmental degradation with its causes. The primary aim of the project was to develop an evidence-based approach in which suites of easy-to-use, cost-effective and environmentally valid biological responses (biomarkers) could be used together to assess the health of coastal systems through the general condition of individuals. A range of sub-lethal endpoints, chosen to reflect successive levels of biological organisation (molecular, cellular, physiological), was evaluated in common coastal organisms showing different feeding types (filter feeding, grazing, predation) and habitat requirements (estuary, rocky shore). Initially, the suite of biomarkers was used in laboratory studies to determine the relative sensitivities of key species within different functional groups to common contaminants. These results were then validated in field studies performed in a range of ecosystems exhibiting different degrees/signatures of contamination. Here, an example is provided of a field study in the Humber Estuary, UK, which illustrates how multivariate statistical analysis can be used to identify patterns of response to discriminate between contaminated and clean sites. The use of a holistic, integrated approach of this kind is advocated as a practical means of assessing the impact of chemical contamination on organismal health and of ranking the status of marine ecosystems. PMID:16271731

  15. 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

  16. Dual Functions, Clamp Opening and Primer-Template Recognition, Define a Key Clamp Loader Subunit

    PubMed Central

    Coman, Maria Magdalena; Jin, Mi; Ceapa, Razvan; Finkelstein, Jeff; O'Donnell, Michael; Chait, Brian T.; Hingorani, Manju M.

    2010-01-01

    Clamp loader proteins catalyze assembly of circular sliding clamps on DNA to enable processive DNA replication. During the reaction, the clamp loader binds primer-template DNA and positions it in the center of a clamp to form a topological link between the two. Clamp loaders are multi-protein complexes, such as the five protein Escherichia coli, Saccharomyces cerevisiae, and human clamp loaders, and the two protein Pyrococcus furiosus and Methanobacterium thermoautotrophicum clamp loaders, and thus far the site(s) responsible for binding and selecting primer-template DNA as the target for clamp assembly remain unknown. To address this issue, we analyzed the interaction between the E. coli γ complex clamp loader and DNA using UV-induced protein–DNA cross-linking and mass spectrometry. The results show that the δ subunit in the γ complex makes close contact with the primer-template junction. Tryptophan 279 in the δ C-terminal domain lies near the 3′-OH primer end and may play a key role in primer-template recognition. Previous studies have shown that δ also binds and opens the β clamp (hydrophobic residues in the N-terminal domain of δ contact β. The clamp-binding and DNA-binding sites on δ appear positioned for facile entry of primer-template into the center of the clamp and exit of the template strand from the complex. A similar analysis of the S. cerevisiae RFC complex suggests that the dual functionality observed for δ in the γ complex may be true also for clamp loaders from other organisms. PMID:15364574

  17. 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. PMID:24656047

  18. 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

  19. 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.

  20. 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

  1. 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

  2. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus

    PubMed Central

    Graham, Robert R.; Kyogoku, Chieko; Sigurdsson, Snaevar; Vlasova, Irina A.; Davies, Leela R. L.; Baechler, Emily C.; Plenge, Robert M.; Koeuth, Thearith; Ortmann, Ward A.; Hom, Geoffrey; Bauer, Jason W.; Gillett, Clarence; Burtt, Noel; Cunninghame Graham, Deborah S.; Onofrio, Robert; Petri, Michelle; Gunnarsson, Iva; Svenungsson, Elisabet; Rönnblom, Lars; Nordmark, Gunnel; Gregersen, Peter K.; Moser, Kathy; Gaffney, Patrick M.; Criswell, Lindsey A.; Vyse, Timothy J.; Syvänen, Ann-Christine; Bohjanen, Paul R.; Daly, Mark J.; Behrens, Timothy W.; Altshuler, David

    2007-01-01

    Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3′ UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease. PMID:17412832

  3. 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.

  4. Defining an abrasion index for lunar surface systems as a function of dust interaction modes and variable concentration zones

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    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 sub-categorically 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.

  5. 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

  6. 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

  7. 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

    2016-01-01

    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. PMID:26785759

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

    PubMed Central

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

    2016-01-01

    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. PMID:26785759

  9. A Comparative Structure/Function Analysis of Two Type IV Pilin DNA Receptors Defines a Novel Mode of DNA Binding.

    PubMed

    Berry, Jamie-Lee; Xu, Yingqi; Ward, Philip N; Lea, Susan M; Matthews, Stephen J; Pelicic, Vladimir

    2016-06-01

    DNA transformation is a widespread process allowing bacteria to capture free DNA by using filamentous nano-machines composed of type IV pilins. These proteins can act as DNA receptors as demonstrated by the finding that Neisseria meningitidis ComP minor pilin has intrinsic DNA-binding ability. ComP binds DNA better when it contains the DNA-uptake sequence (DUS) motif abundant in this species genome, playing a role in its trademark ability to selectively take up its own DNA. Here, we report high-resolution structures for meningococcal ComP and Neisseria subflava ComPsub, which recognize different DUS motifs. We show that they are structurally identical type IV pilins that pack readily into filament models and display a unique DD region delimited by two disulfide bonds. Functional analysis of ComPsub defines a new mode of DNA binding involving the DD region, adapted for exported DNA receptors. PMID:27161979

  10. Recovering functions defined on the unit sphere by integration on a special family of sub-spheres

    NASA Astrophysics Data System (ADS)

    Salman, Yehonatan

    2016-05-01

    The aim of this article is to derive a reconstruction formula for the recovery of C1 functions, defined on the unit sphere {{{S}}}^{n - 1} , given their integrals on a special family of n - 2 dimensional sub-spheres. For a fixed point overline{a} strictly inside {{{S}}}^{n - 1} , each sub-sphere in this special family is obtained by intersection of {{{S}}}^{n - 1} with a hyperplane passing through overline{a} . The case overline{a} = 0 results in an inversion formula for the special case of integration on great spheres (i.e., Funk transform). The limiting case where pin {{{S}}}^{n - 1} and overline{a}→ p results in an inversion formula for the special case of integration on spheres passing through a common point in {{{S}}}^{n - 1}.

  11. 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

  12. Comparative genomics using teleost fish helps to systematically identify target gene bodies of functionally defined human enhancers

    PubMed Central

    2013-01-01

    Background Human genome is enriched with thousands of conserved non-coding elements (CNEs). Recently, a medium throughput strategy was employed to analyze the ability of human CNEs to drive tissue specific expression during mouse embryogenesis. These data led to the establishment of publicly available genome wide catalog of functionally defined human enhancers. Scattering of enhancers over larger regions in vertebrate genomes seriously impede attempts to pinpoint their precise target genes. Such associations are prerequisite to explore the significance of this in vivo characterized catalog of human enhancers in development, disease and evolution. Results This study is an attempt to systematically identify the target gene-bodies for functionally defined human CNE-enhancers. For the purpose we adopted the orthology/paralogy mapping approach and compared the CNE induced reporter expression with reported endogenous expression pattern of neighboring genes. This procedure pinpointed specific target gene-bodies for the total of 192 human CNE-enhancers. This enables us to gauge the maximum genomic search space for enhancer hunting: 4 Mb of genomic sequence around the gene of interest (2 Mb on either side). Furthermore, we used human-rodent comparison for a set of 159 orthologous enhancer pairs to infer that the central nervous system (CNS) specific gene expression is closely associated with the cooperative interaction among at least eight distinct transcription factors: SOX5, HFH, SOX17, HNF3β, c-FOS, Tal1beta-E47S, MEF and FREAC. Conclusions In conclusion, the systematic wiring of cis-acting sites and their target gene bodies is an important step to unravel the role of in vivo characterized catalog of human enhancers in development, physiology and medicine. PMID:23432897

  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. A Diagrammatic Proof That Indirect Utility Functions Are Quasi-Convex.

    ERIC Educational Resources Information Center

    Suen, Wing

    1992-01-01

    Presents a diagrammatic proof for classroom use to demonstrate the quasi-convexity of the indirect utility function. Includes a variation of the price indifference curve. Suggests an exercise in which the student is asked to show that the tangency condition is a restatement of Roy's identity. (DK)

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

    DOE PAGESBeta

    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

  16. 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.

  17. 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.

  18. 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

  19. How to use individual differences to isolate functional organization, biology, and utility of visual functions; with illustrative proposals for stereopsis

    PubMed Central

    Wilmer, Jeremy B.

    2008-01-01

    This paper is a call for greater use of individual differences in the basic science of visual perception. Individual differences yield insights into visual perception’s functional organization, underlying biological/environmental mechanisms, and utility. I first explain the general approach advocated and where it comes from. Second, I describe five principles central to learning about the nature of visual perception through individual differences. Third, I elaborate on the use of individual differences to gain insights into the three areas mentioned above (function, biology/environment, utility), in each case describing the approach advocated, presenting model examples from the literature, and laying out illustrative research proposals for the case of stereopsis. PMID:19017483

  20. High-functioning autism and Asperger's disorder: utility and meaning for families.

    PubMed

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

    2012-02-01

    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 advantages of AD and AsD diagnosis were increased understanding and practical support, and parental empowerment. Disadvantages included the effects of stigma and concerns about validity. Participants tended to consider AsD and AD as interchangeable terms. Findings suggest that the utility of AD and AsD depends upon both their validity and how these diagnoses are received in their cultural, economic and legislative context. Improvement of post-diagnostic services will improve the utility of AD and AsD. PMID:21472359

  1. 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

  2. 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…

  3. 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

  4. Utility of the International Classification of Functioning, Disability and Health (ICF) for educational psychologists’ work

    PubMed Central

    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 with children who have Autism Spectrum Disorders (ASD). Mothers of 40 children with ASD aged eight to 12 years were interviewed using a structured protocol based on the ICF framework. The Diagnostic Interview for Social and Communication Disorder (DISCO) was completed with a subset of 19 mothers. Internal consistency and inter-rater reliability of the interview assessments were found to be acceptable and there was evidence for concurrent and discriminant validity. Despite some limitations, initial support for the utility of the ICF model suggests its potential value across educational, health and care fields. Further consideration of its relevance to educational psychologists in new areas of multi-agency working is warranted. PMID:26157197

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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

  10. Wound Tissue Can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin

    NASA Astrophysics Data System (ADS)

    Yannas, I. V.; Burke, J. F.; Orgill, D. P.; Skrabut, E. M.

    1982-01-01

    Prompt and long-term closure of full-thickness skin wounds in guinea pigs and humans is achieved by applying a bilayer polymeric membrane. The membrane comprises a top layer of a silicone elastomer and a bottom layer of a porous cross-linked network of collagen and glycosaminoglycan. The bottom layer can be seeded with a small number of autologous basal cells before grafting. No immunosuppression is used and infection, exudation, and rejection are absent. Host tissue utilizes the sterile membrane as a culture medium to synthesize neoepidermal and neodermal tissue. A functional extension of skin over the entire wound area is formed in about 4 weeks.

  11. 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. PMID:26969977

  12. Functional characterization of polysaccharide utilization loci in the marine Bacteroidetes 'Gramella forsetii' KT0803.

    PubMed

    Kabisch, Antje; Otto, Andreas; König, Sten; Becher, Dörte; Albrecht, Dirk; Schüler, Margarete; Teeling, Hanno; Amann, Rudolf I; Schweder, Thomas

    2014-07-01

    Members of the phylum Bacteroidetes are abundant in many marine ecosystems and are known to have a pivotal role in the mineralization of complex organic substrates such as polysaccharides and proteins. We studied the decomposition of the algal glycans laminarin and alginate by 'Gramella forsetii' KT0803, a bacteroidetal isolate from North Sea surface waters. A combined application of isotope labeling, subcellular protein fractionation and quantitative proteomics revealed two large polysaccharide utilization loci (PULs) that were specifically induced, one by alginate and the other by laminarin. These regulons comprised genes of surface-exposed proteins such as oligomer transporters, substrate-binding proteins, carbohydrate-active enzymes and hypothetical proteins. Besides, several glycan-specific TonB-dependent receptors and SusD-like substrate-binding proteins were expressed also in the absence of polysaccharide substrates, suggesting an anticipatory sensing function. Genes for the utilization of the beta-1,3-glucan laminarin were found to be co-regulated with genes for glucose and alpha-1,4-glucan utilization, which was not the case for the non-glucan alginate. Strong syntenies of the PULs of 'G. forsetii' with similar loci in other Bacteroidetes indicate that the specific response mechanisms of 'G. forsetii' to changes in polysaccharide availability likely apply to other Bacteroidetes. Our results can thus contribute to an improved understanding of the ecological niches of marine Bacteroidetes and their roles in the polysaccharide decomposition part of carbon cycling in marine ecosystems. PMID:24522261

  13. 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.

  14. 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% ...

  15. Defining Risk.

    ERIC Educational Resources Information Center

    Tholkes, Ben F.

    1998-01-01

    Defines camping risks and lists types and examples: (1) objective risk beyond control; (2) calculated risk based on personal choice; (3) perceived risk; and (4) reckless risk. Describes campers to watch ("immortals" and abdicators), and several "treatments" of risk: avoidance, safety procedures and well-trained staff, adequate insurance, and a…

  16. DSM-IV-Defined Asperger Syndrome: Cognitive, Behavioral and Early History Differentiation from High-Functioning Autism.

    ERIC Educational Resources Information Center

    Ozonoff, Sally; South, Mikle; Miller, Judith N.

    2000-01-01

    This study compared 23 children with high-functioning autism with 12 children with Asperger syndrome using DSM-IV diagnostic criteria. Findings indicated few group differences in current functioning but many early history differences. The Asperger syndrome group generally demonstrated less severe early symptoms, a milder developmental course, and…

  17. 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. PMID:21661023

  18. 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

  19. Structure, function, and regulation of the aldouronate utilization gene cluster from Paenibacillus sp. strain JDR-2.

    PubMed

    Chow, Virginia; Nong, Guang; Preston, James F

    2007-12-01

    Direct bacterial conversion of the hemicellulose fraction of hardwoods and crop residues to biobased products depends upon extracellular depolymerization of methylglucuronoxylan (MeGAX(n)), followed by assimilation and intracellular conversion of aldouronates and xylooligosaccharides to fermentable xylose. Paenibacillus sp. strain JDR-2, an aggressively xylanolytic bacterium, secretes a multimodular cell-associated GH10 endoxylanase (XynA1) that catalyzes depolymerization of MeGAX(n) and rapidly assimilates the principal products, beta-1,4-xylobiose, beta-1,4-xylotriose, and MeGAX(3), the aldotetrauronate 4-O-methylglucuronosyl-alpha-1,2-xylotriose. Genomic libraries derived from this bacterium have now allowed cloning and sequencing of a unique aldouronate utilization gene cluster comprised of genes encoding signal transduction regulatory proteins, ABC transporter proteins, and the enzymes AguA (GH67 alpha-glucuronidase), XynA2 (GH10 endoxylanase), and XynB (GH43 beta-xylosidase/alpha-arabinofuranosidase). Expression of these genes, as well as xynA1 encoding the secreted GH10 endoxylanase, is induced by growth on MeGAX(n) and repressed by glucose. Sequences in the yesN, lplA, and xynA2 genes within the cluster and in the distal xynA1 gene show significant similarity to catabolite responsive element (cre) defined in Bacillus subtilis for recognition of the catabolite control protein (CcpA) and consequential repression of catabolic regulons. The aldouronate utilization gene cluster in Paenibacillus sp. strain JDR-2 operates as a regulon, coregulated with the expression of xynA1, conferring the ability for efficient assimilation and catabolism of the aldouronate product generated by a multimodular cell surface-anchored GH10 endoxylanase. This cluster offers a desirable metabolic potential for bacterial conversion of hemicellulose fractions of hardwood and crop residues to biobased products. PMID:17921311

  20. 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. PMID:26102555

  1. Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing.

    PubMed

    Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

    2015-01-01

    It is unknown if the white-matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white-matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white-matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white-matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

  2. Functionally defined white matter reveals segregated pathways in human ventral temporal cortex associated with category-specific processing

    PubMed Central

    Gomez, Jesse; Pestilli, Franco; Witthoft, Nathan; Golarai, Golijeh; Liberman, Alina; Poltoratski, Sonia; Yoon, Jennifer; Grill-Spector, Kalanit

    2014-01-01

    Summary It is unknown if the white matter properties associated with specific visual networks selectively affect category-specific processing. In a novel protocol we combined measurements of white matter structure, functional selectivity, and behavior in the same subjects. We find two parallel white matter pathways along the ventral temporal lobe connecting to either face-selective or place-selective regions. Diffusion properties of portions of these tracts adjacent to face- and place-selective regions of ventral temporal cortex correlate with behavioral performance for face or place processing, respectively. Strikingly, adults with developmental prosopagnosia (face blindness) express an atypical structure-behavior relationship near face-selective cortex, suggesting that white matter atypicalities in this region may have behavioral consequences. These data suggest that examining the interplay between cortical function, anatomical connectivity, and visual behavior is integral to understanding functional networks and their role in producing visual abilities and deficits. PMID:25569351

  3. 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

  4. 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.

  5. 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

  6. Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils

    PubMed Central

    Zhang, Mai; Angata, Takashi; Cho, Jae Youn; Miller, Marina; Broide, David H.

    2007-01-01

    CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4+ cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F–null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti–Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders. PMID:17272508

  7. 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

  8. 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.

  9. 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. PMID:27193299

  10. The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease.

    PubMed

    Reijns, Martin A M; Bubeck, Doryen; Gibson, Lucien C D; Graham, Stephen C; Baillie, George S; Jones, E Yvonne; Jackson, Andrew P

    2011-03-25

    Ribonuclease H2 (RNase H2) is the major nuclear enzyme involved in the degradation of RNA/DNA hybrids and removal of ribonucleotides misincorporated in genomic DNA. Mutations in each of the three RNase H2 subunits have been implicated in a human auto-inflammatory disorder, Aicardi-Goutières Syndrome (AGS). To understand how mutations impact on RNase H2 function we determined the crystal structure of the human heterotrimer. In doing so, we correct several key regions of the previously reported murine RNase H2 atomic model and provide biochemical validation for our structural model. Our results provide new insights into how the subunits are arranged to form an enzymatically active complex. In particular, we establish that the RNASEH2A C terminus is a eukaryotic adaptation for binding the two accessory subunits, with residues within it required for enzymatic activity. This C-terminal extension interacts with the RNASEH2C C terminus and both are necessary to form a stable, enzymatically active heterotrimer. Disease mutations cluster at this interface between all three subunits, destabilizing the complex and/or impairing enzyme activity. Altogether, we locate 25 out of 29 residues mutated in AGS patients, establishing a firm basis for future investigations into disease pathogenesis and function of the RNase H2 enzyme. PMID:21177854

  11. 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

  12. Utilization of Substrate Intrinsic Binding Energy for Conformational Change and Catalytic Function in Phosphoenolpyruvate Carboxykinase.

    PubMed

    Johnson, Troy A; Mcleod, Matthew J; Holyoak, Todd

    2016-01-26

    Phosphoenolpyruvate carboxykinase (PEPCK) is an essential metabolic enzyme operating in the gluconeogenesis and glyceroneogenesis pathways. Previous work has demonstrated that the enzyme cycles between a catalytically inactive open state and a catalytically active closed state. The transition of the enzyme between these states requires the transition of several active site loops to shift from mobile, disordered structural elements to stable ordered states. The mechanism by which these disorder-order transitions are coupled to the ligation state of the active site however is not fully understood. To further investigate the mechanisms by which the mobility of the active site loops is coupled to enzymatic function and the transitioning of the enzyme between the two conformational states, we have conducted structural and functional studies of point mutants of E89. E89 is a proposed key member of the interaction network of mobile elements as it resides in the R-loop region of the enzyme active site. These new data demonstrate the importance of the R-loop in coordinating interactions between substrates at the OAA/PEP binding site and the mobile R- and Ω-loop domains. In turn, the studies more generally demonstrate the mechanisms by which the intrinsic ligand binding energy can be utilized in catalysis to drive unfavorable conformational changes, changes that are subsequently required for both optimal catalytic activity and fidelity. PMID:26709450

  13. Relations between Brain Structure and Attentional Function in Spina Bifida: Utilization of Robust Statistical Approaches

    PubMed Central

    Kulesz, Paulina A.; Tian, Siva; Juranek, Jenifer; Fletcher, Jack M.; Francis, David J.

    2015-01-01

    Objective Weak structure-function relations for brain and behavior may stem from problems in estimating these relations in small clinical samples with frequently occurring outliers. In the current project, we focused on the utility of using alternative statistics to estimate these relations. Method Fifty-four children with spina bifida meningomyelocele performed attention tasks and received MRI of the brain. Using a bootstrap sampling process, the Pearson product moment correlation was compared with four robust correlations: the percentage bend correlation, the Winsorized correlation, the skipped correlation using the Donoho-Gasko median, and the skipped correlation using the minimum volume ellipsoid estimator Results All methods yielded similar estimates of the relations between measures of brain volume and attention performance. The similarity of estimates across correlation methods suggested that the weak structure-function relations previously found in many studies are not readily attributable to the presence of outlying observations and other factors that violate the assumptions behind the Pearson correlation. Conclusions Given the difficulty of assembling large samples for brain-behavior studies, estimating correlations using multiple, robust methods may enhance the statistical conclusion validity of studies yielding small, but often clinically significant, correlations. PMID:25495830

  14. 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.

  15. 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

  16. 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.

  17. 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…

  18. 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

  19. Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging

    PubMed Central

    Mayka, Mary A.; Corcos, Daniel M.; Leurgans, Sue E.; Vaillancourt, David E.

    2007-01-01

    The mesial premotor cortex (pre-supplementary motor area and supplementary motor area proper), lateral premotor cortex (dorsal premotor cortex and ventral premotor cortex), and primary sensorimotor cortex (primary motor cortex and primary somatosensory cortex) have been identified as key cortical areas for sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries between these regions remain unclear. In order to clarify the locations and boundaries for these six sensorimotor regions, we surveyed 126 articles describing pre-supplementary motor area, supplementary motor area proper, dorsal premotor cortex, ventral premotor cortex, primary motor cortex, and primary somatosensory cortex. Using strict inclusion criteria, we recorded the reported normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each experiment. We then computed the probability distributions describing the likelihood of activation, and characterized the shape, extent, and area of each sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap between the six sensorimotor regions. Using the findings from this meta-analysis, along with suggestions and guidelines of previous researchers, we developed the Human Motor Area Template (HMAT) that can be used for ROI analysis. PMID:16571375

  20. The Utilization of Amide Groups To Expand and Functionalize Metal-Organic Frameworks Simultaneously.

    PubMed

    Lu, Zhiyong; Bai, Junfeng; Hang, Cheng; Meng, Fei; Liu, Wenlong; Pan, Yi; You, Xiaozeng

    2016-04-25

    A new stepwise ligand-elongation strategy by amide spacers is utilized to prepare isoreticularly high-porous metal-organic frameworks (MOFs), namely, quasi-mesoporous [Cu2 (PDBAD)(H2 O)]n (H4 PDBAD=5,5'-((4,4'-((pyridine-3,5-dicarbonyl)bis(azanediyl))bis(benzoyl))bis(azanediyl))diisophthalic acid; NJU-Bai22: NJU-Bai for Nanjing University Bai's group), and mesoporous [Cu2 (PABAD)(H2 O)]n (H4 PABAD=5,5'-((4,4'-((4,4'-((pyridine-3,5-dicarbonyl)bis(azanediyl))bis(benzoyl))bis (azanediyl))bis(benzoyl))bis(azanediyl))diisophthalic acid; NJU-Bai23). Compared with the prototypical MOF of [Cu2 (PDAD)(H2 O)]n (H4 PDAD=5,5'-(pyridine-3,5-dicarbonyl)bis(azanediyl)diisophthalic acid; NJU-Bai21, also termed as PCN-124), both MOFs exhibit almost the same CO2 adsorption enthalpy and CO2 selectivity values, and better capacity for CO2 storage under high pressure; these results make them promising candidate materials for CO2 capture and sequestration. Interestingly, this new method, in comparison with traditional strategies of using phenyl or triple-bond spacers, is easier and cheaper, resulting in a better ability to retain high CO2 affinity and selectivity in MOFs with large pores and high CO2 storage capacity. Additionally, it may lead to the high thermal stability of the MOFs and also their tolerance to water, which is related to the balance between the density of functional groups and pore sizes. Therefore, this strategy could provide new opportunities to explore more functionalized mesoporous MOFs with high performance. PMID:27031809

  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. PMID:27061212

  2. 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.

  3. 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.

  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. 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.

  6. Social Service Utilization, Sense of Community, Family Functioning and the Mental Health of New Immigrant Women in Hong Kong

    PubMed Central

    Wu, Qiaobing; Chow, Julian Chun-Chung

    2013-01-01

    Drawing upon a sample of 296 new immigrant women in Hong Kong, this study investigated how social service utilization, family functioning, and sense of community influenced the depressive symptoms of new immigrant women. Results of the structural equation modeling suggested that family functioning and sense of community were both significantly and negatively associated with the depression of new immigrant women. Utilization of community services also influenced the depression of immigrant women indirectly through the mediating effect of sense of community. Implications of the research findings for mental health intervention were discussed. PMID:23629592

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

    PubMed Central

    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

    2015-01-01

    Summary 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

  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. The utility of pulmonary function testing in predicting outcomes following liver transplantation.

    PubMed

    Kia, Leila; Cuttica, Michael J; Yang, Amy; Donnan, Erica N; Whitsett, Maureen; Singhvi, Ajay; Lemmer, Alexander; Levitsky, Josh

    2016-06-01

    Although pulmonary function tests (PFTs) are routinely performed in patients during the evaluation period before liver transplantation (LT), their utility in predicting post-LT mortality and morbidity outcomes is not known. The aim of this study was to determine the impact of obstructive and/or restrictive lung disease on post-LT outcomes. We conducted a retrospective analysis of patients who had pre-LT PFTs and underwent a subsequent LT (2007-2013). We used statistical analyses to determine independent associations between PFT parameters and outcomes (graft/patient survival, time on ventilator, and hospital/intensive care unit [ICU] length of stay [LOS]). A total of 415 LT recipients with available PFT data were included: 65% of patients had normal PFTs; 8% had obstructive lung disease; and 27% had restrictive lung disease. There was no difference in patient and graft survival between patients with normal, obstructive, and restrictive lung disease. However, restrictive lung disease was associated with longer post-LT time on ventilator and both ICU and hospital LOS (P < 0.05). More specific PFT parameters (diffusing capacity of the lungs for carbon monoxide, total lung capacity, and residual volume) were all significant predictors of ventilator time and both ICU and hospital LOS (P < 0.05). Although pre-LT PFT parameters may not predict post-LT mortality, restrictive abnormalities correlate with prolonged post-LT ventilation and LOS. Efforts to identify and minimize the impact of restrictive abnormalities on PFTs might improve such outcomes. Liver Transplantation 22 805-811 2016 AASLD. PMID:26929108

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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…

  17. 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…

  18. 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

  19. Labview utilities

    Energy Science and Technology Software Center (ESTSC)

    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.

  20. Evaluation of the utility of a discrete-trial functional analysis in early intervention classrooms.

    PubMed

    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. PMID:24114103

  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. Benchmarking the performance of density functional theory based Green's function formalism utilizing different self-energy models in calculating electronic transmission through molecular systems.

    PubMed

    Prociuk, Alexander; Van Kuiken, Ben; Dunietz, Barry D

    2006-11-28

    Electronic transmission through a metal-molecule-metal system is calculated by employing a Green's function formalism in the scattering based scheme. Self-energy models representing the bulk and the potential bias are used to describe electron transport through the molecular system. Different self-energies can be defined by varying the partition between device and bulk regions of the metal-molecule-metal model system. In addition, the self-energies are calculated with different representations of the bulk through its Green's function. In this work, the dependence of the calculated transmission on varying the self-energy subspaces is benchmarked. The calculated transmission is monitored with respect to the different choices defining the self-energy model. In this report, we focus on one-dimensional model systems with electronic structures calculated at the density functional level of theory. PMID:17144733

  3. Strategy Development and Utilization in Concept Identification as a Function of an Individual's Cognitive Style.

    ERIC Educational Resources Information Center

    Davis, J. Kent

    Reported is an experiment undertaken to determine the extent to which analytic and global cognitive styles differed in developing or utilizing a selection type strategy in concept identification. Using the Hidden Figures Test (HFT) in five sections of an introductory psychology class, two groups of students, one analytical and one global, were…

  4. Increasing the Utility of EF Assessment of Executive Function in Children

    ERIC Educational Resources Information Center

    Salimpoor, Valorie Niloufar; Desrocher, Mary

    2006-01-01

    Executive functions (EF) are a group of interrelated complex mental abilities that are involved in planning and initiating goals and carrying them through despite interruptions. As these functions are typically higher-order and involved in integrating other, more basic, lower-order functions, they are difficult to assess directly, and executive…

  5. 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

  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. 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

  8. A functional myo-inositol catabolism pathway is essential for rhizopine utilization by Sinorhizobium meliloti.

    PubMed

    Galbraith, M P; Feng, S F; Borneman, J; Triplett, E W; de Bruijn, F J; Rossbach, S

    1998-10-01

    Rhizopine (L-3-O-methyl-scyllo-inosamine) is a symbiosis-specific compound found in alfalfa nodules induced by specific Sinorhizobium meliloti strains. It has been postulated that rhizobial strains able to synthesize and catabolize rhizopine gain a competitive advantage in the rhizosphere. The pathway of rhizopine degradation is analysed here. Since rhizopine is an inositol derivative, it was tested whether inositol catabolism is involved in rhizopine utilization. A genetic locus required for the catabolism of inositol as sole carbon source was cloned from S. meliloti. This locus was delimited by transposon Tn5 mutagenesis and its DNA sequence was determined. Based on DNA similarity studies and enzyme assays, this genetic region was shown to encode an S. meliloti myo-inositol dehydrogenase. Strains that harboured a mutation in the myo-inositol dehydrogenase gene (idhA) did not display myo-inositol dehydrogenase activity, were unable to utilize myo-inositol as sole carbon/energy source, and were unable to catabolize rhizopine. Thus, myo-inositol dehydrogenase activity is essential for rhizopine utilization in S. meliloti. PMID:9802033

  9. Gigantic enhancement in response and reset time of ZnO UV nanosensor by utilizing Schottky contact and surface functionalization

    PubMed Central

    Zhou, Jun; Gu, Yudong; Hu, Youfan; Mai, Wenjie; Yeh, Ping-Hung; Bao, Gang; Sood, Ashok K.; Polla, Dennis L.; Wang, Zhong Lin

    2009-01-01

    UV response of ZnO nanowire nanosensor has been studied under ambient condition. By utilizing Schottky contact instead of Ohmic contact in device fabrication, the UV sensitivity of the nanosensor has been improved by four orders of magnitude, and the reset time has been drastically reduced from ∼417 to ∼0.8 s. By further surface functionalization with function polymers, the reset time has been reduced to ∼20 ms even without correcting the electronic response of the measurement system. These results demonstrate an effective approach for building high response and fast reset UV detectors. PMID:19654881

  10. 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.

  11. Treatment Utility of Functional versus Empiric Assessment within Consultation for Reading Problems

    ERIC Educational Resources Information Center

    Beavers, Karen F.; Kratochwill, Thomas R.; Braden, Jeffery P.

    2004-01-01

    In this study, 18 teachers and 32 of their students who had reading difficulties were randomly assigned to one of two assessment conditions. In the functional assessment condition, consultants identified functional relationships among environmental events and targeted reading behaviors to develop an intervention plan. In the empiric condition,…

  12. nanoCAGE reveals 5′ UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs

    PubMed Central

    Gandin, Valentina; Masvidal, Laia; Hulea, Laura; Gravel, Simon-Pierre; Cargnello, Marie; McLaughlan, Shannon; Cai, Yutian; Balanathan, Preetika; Morita, Masahiro; Rajakumar, Arjuna; Furic, Luc; Pollak, Michael; Porco, John A.; St-Pierre, Julie; Pelletier, Jerry; Larsson, Ola; Topisirovic, Ivan

    2016-01-01

    The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5′ TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5′ TOP motif but that 5′ UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5′ UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5′ UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5′ UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5′ UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5′ UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells. PMID:26984228

  13. 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

  14. nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.

    PubMed

    Gandin, Valentina; Masvidal, Laia; Hulea, Laura; Gravel, Simon-Pierre; Cargnello, Marie; McLaughlan, Shannon; Cai, Yutian; Balanathan, Preetika; Morita, Masahiro; Rajakumar, Arjuna; Furic, Luc; Pollak, Michael; Porco, John A; St-Pierre, Julie; Pelletier, Jerry; Larsson, Ola; Topisirovic, Ivan

    2016-05-01

    The diversity of MTOR-regulated mRNA translation remains unresolved. Whereas ribosome-profiling suggested that MTOR almost exclusively stimulates translation of the TOP (terminal oligopyrimidine motif) and TOP-like mRNAs, polysome-profiling indicated that MTOR also modulates translation of mRNAs without the 5' TOP motif (non-TOP mRNAs). We demonstrate that in ribosome-profiling studies, detection of MTOR-dependent changes in non-TOP mRNA translation was obscured by low sensitivity and methodology biases. Transcription start site profiling using nano-cap analysis of gene expression (nanoCAGE) revealed that not only do many MTOR-sensitive mRNAs lack the 5' TOP motif but that 5' UTR features distinguish two functionally and translationally distinct subsets of MTOR-sensitive mRNAs: (1) mRNAs with short 5' UTRs enriched for mitochondrial functions, which require EIF4E but are less EIF4A1-sensitive; and (2) long 5' UTR mRNAs encoding proliferation- and survival-promoting proteins, which are both EIF4E- and EIF4A1-sensitive. Selective inhibition of translation of mRNAs harboring long 5' UTRs via EIF4A1 suppression leads to sustained expression of proteins involved in respiration but concomitant loss of those protecting mitochondrial structural integrity, resulting in apoptosis. Conversely, simultaneous suppression of translation of both long and short 5' UTR mRNAs by MTOR inhibitors results in metabolic dormancy and a predominantly cytostatic effect. Thus, 5' UTR features define different modes of MTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells. PMID:26984228

  15. The Utility of the HSAB Principle via the Fukui Function in Biological Systems

    PubMed Central

    Faver, John; Merz, Kenneth M.

    2010-01-01

    The hard/soft acid-base principle has long been known to be an excellent predictor of chemical reactivity. The Fukui function, a reactivity descriptor from conceptual density functional theory, has been shown to be related to the local softness of a system. The usefulness of the Fukui function is explored and demonstrated herein for three common biological problems: ligand docking, active site detection, and protein folding. In each type of study, a scoring function is developed based on the local HSAB principle using atomic Fukui indices. Even with necessary approximations for its use in large systems, the Fukui function remains a useful descriptor for predicting chemical reactivity and understanding chemical systems. PMID:20369029

  16. 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.

  17. 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

  18. 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.

  19. Three years of antibacterial consumption in Indonesian Community Health Centers: The application of anatomical therapeutic chemical/defined daily doses and drug utilization 90% method to monitor antibacterial use

    PubMed Central

    Pradipta, Ivan S.; Ronasih, Elis; Kartikawati, Arrum D.; Hartanto, Hartanto; Amelia, Rizki; Febrina, Ellin; Abdulah, Rizky

    2015-01-01

    Context: Irrational use of antibacterial drugs in Community Health-Care Centers (CHCs) may lead to increased resistance, morbidity, and mortality. Aims: The aim of this study was to determine patterns of antibacterial use at CHCs in a district of Indonesia and use this as data for an antibiotic policy. Settings and Design: The observational-descriptive study was conducted in a district of Indonesia to obtain antibacterial use from 2008 to 2010. Subjects and Methods: The data obtained from the report on the use of medicines were classified and processed using the anatomical therapeutic chemical (ATC) and defined daily doses (DDD) method, with DDD/1000 patients as a unit measurement. The number of patients was obtained from attending patients in that research period. The most abundant antibacterial drugs use segment was identified by the drug utilization 90% (DU90%) method. Statistical Analysis Used: Descriptive analysis were performed in this study. Results: Fourteen kinds of antibacterial drugs were used in 61 CHCs. The total of antibacterial drug use during the period 2008–2010 was 871.36 DDD/1000 patients/day. Declining antibacterial use was observed between 2008 and 2010. Six kinds of antibacterial drugs were the most commonly used. The data show that the average use per visit was as high as 24.41 DDD. Conclusions: Amoxicillin, sulfamethoxazole and trimethoprim are antibacterials that have to be reconsidered by physicians for use in the Bandung CHC. The high use of antibacterial drugs, as described in the study, can be used as reference to develop an antimicrobial stewardship program and increase awareness of resistance, adverse drug reaction and drug interaction of antibacterial drugs. PMID:25983606

  20. Supraspliceosomes at Defined Functional States Portray the Pre-Assembled Nature of the Pre-mRNA Processing Machine in the Cell Nucleus

    PubMed Central

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

    2014-01-01

    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. PMID:24983480

  1. 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

  2. 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.

  3. 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

  4. Dimensional feature weighting utilizing multiple kernel learning for single-channel talker location discrimination using the acoustic transfer function.

    PubMed

    Takashima, Ryoichi; Takiguchi, Tetsuya; Ariki, Yasuo

    2013-02-01

    This paper presents a method for discriminating the location of the sound source (talker) using only a single microphone. In a previous work, the single-channel approach for discriminating the location of the sound source was discussed, where the acoustic transfer function from a user's position is estimated by using a hidden Markov model of clean speech in the cepstral domain. In this paper, each cepstral dimension of the acoustic transfer function is newly weighted, in order to obtain the cepstral dimensions having information that is useful for classifying the user's position. Then, this paper proposes a feature-weighting method for the cepstral parameter using multiple kernel learning, defining the base kernels for each cepstral dimension of the acoustic transfer function. The user's position is trained and classified by support vector machine. The effectiveness of this method has been confirmed by sound source (talker) localization experiments performed in different room environments. PMID:23363107

  5. Tumor Functional and Molecular Imaging Utilizing Ultrasound and Ultrasound-Mediated Optical Techniques

    PubMed Central

    Yuan, Baohong; Rychak, Joshua

    2014-01-01

    Tumor functional and molecular imaging has significantly contributed to cancer preclinical research and clinical applications. Among typical imaging modalities, ultrasonic and optical techniques are two commonly used methods; both share several common features such as cost efficiency, absence of ionizing radiation, relatively inexpensive contrast agents, and comparable maximum-imaging depth. Ultrasonic and optical techniques are also complementary in imaging resolution, molecular sensitivity, and imaging space (vascular and extravascular). The marriage between ultrasonic and optical techniques takes advantages of both techniques. This review introduces tumor functional and molecular imaging using microbubble-based ultrasound and ultrasound-mediated optical imaging techniques. PMID:23219728

  6. 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

  7. 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.

  8. Utility of the Mantel-Haenszel Procedure for Detecting Differential Item Functioning in Small Samples

    ERIC Educational Resources Information Center

    Fidalgo, Angel M.; Ferreres, Doris; Muniz, Jose

    2004-01-01

    Sample-size restrictions limit the contingency table approaches based on asymptotic distributions, such as the Mantel-Haenszel (MH) procedure, for detecting differential item functioning (DIF) in many practical applications. Within this framework, the present study investigated the power and Type I error performance of empirical and inferential…

  9. 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…

  10. Prekindergarten Children's Executive Functioning Skills and Achievement Gains: The Utility of Direct Assessments and Teacher Ratings

    ERIC Educational Resources Information Center

    Fuhs, Mary Wagner; Farran, Dale Clark; Nesbitt, Kimberly Turner

    2015-01-01

    An accumulating body of evidence suggests that young children who exhibit greater executive functioning (EF) skills in early childhood also achieve more academically. The goal of the present study was to examine the unique contributions of direct assessments and teacher ratings of children's EF skills at the beginning of prekindergarten (pre-k) to…

  11. 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…

  12. 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,…

  13. Demonstrating the Utility of a Multilevel Model in the Assessment of Differential Item Functioning.

    ERIC Educational Resources Information Center

    Pommerich, Mary

    When tests contain few items, observed score may not be an accurate reflection of true score, and the Mantel Haenszel (MH) statistic may perform poorly in detecting differential item functioning. Applications of the MH procedure in such situations require an alternate strategy; one such strategy is to include background variables in the matching…

  14. 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.

  15. 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. PMID:25557900

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  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. PMID:25748244

  2. An analysis of the functional health of obese children and adolescents utilizing the PODC instrument.

    PubMed

    Podeszwa, David A; Stanko, Karen J; Mooney, James F; Cramer, Kathryn E; Mendelow, Michael J

    2006-01-01

    Childhood and adolescent obesity is increasing in prevalence and is known to have long-term medical and musculoskeletal consequences. The baseline Pediatric Outcomes Data Collection Instrument (PODCI) was administered to 50 obese patients (>95th percentile BMI for age) or their parent (for those <11 years) presenting to a pediatric orthopaedic clinic to assess overall function. There were no differences between sexes (31 boys, 19 girls) or age group (>11 years, n = 36; <11 years, n = 14) in any demographic or PODCI category. Compared with normative data, there was significant impairment in sports and pain identified in both genders, African-Americans, and those older than 11 years. These findings were consistent when comparing genders, ethnicities, and ages. There was no difference in happiness between any gender, age, or ethnic group. All groups reported essentially neutral satisfaction. There appears to be a lack of self-recognition of or reluctance to admit functional impairment secondary to obesity. Being obese, African-American ethnicity, and age older than 11 years appear to be risk factors for limited, yet significant, functional impairment. PMID:16439920

  3. 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

  4. Development of a cell-defined siRNA microarray for analysis of gene function in human bone marrow stromal cells.

    PubMed

    Kim, Hi Chul; Kim, Gi-Hwan; Cho, Ssang-Goo; Lee, Eun Ju; Kwon, Yong-Jun

    2016-03-01

    Small interfering RNA (siRNA) screening approaches have provided useful tools for the validation of genetic functions; however, image-based siRNA screening using multiwell plates requires large numbers of cells and time, which could be the barrier in application for gene mechanisms study using human adult cells. Therefore, we developed the advanced method with the cell-defined siRNA microarray (CDSM), for functional analysis of genes in small scale within slide glass using human bone marrow stromal cells (hBMSCs). We designed cell spot system with biomaterials (sucrose, gelatin, poly-L-lysine and matrigel) to control the attachment of hBMSCs inside spot area on three-dimensional (3D) hydrogel-coated slides. The p65 expression was used as a validation standard which described our previous report. For the optimization of siRNA mixture, first, we detected five kinds of commercialized reagent (Lipofectamine 2000, RNAi-Max, Metafectine, Metafectine Pro, TurboFectin 8.0) via validation. Then, according to quantification of p65 expression, we selected 2 μl of RNAi-Max as the most effective reagent condition on our system. Using same validation standard, we optimized sucrose and gelatin concentration (80 mM and 0.13%), respectively. Next, we performed titration of siRNA quantity (2.66-5.55 μM) by reverse transfection time (24 h, 48 h, 72 h) and confirmed 3.75 μM siRNA concentration and 48 h as the best condition. To sum up the process for optimized CDSM, 3 μl of 20 μM siRNA (3.75 μM) was transferred to the 384-well V-bottom plate containing 2 μl of dH2O and 2 μl of 0.6M sucrose (80 mM). Then, 2 μl of RNAi-Max was added and incubated for 20 min at room temperature after mixing gently and centrifugation shortly. Five microliters of gelatin (0.26%) and 2 μl of growth factor reduced phenol red-free matrigel (12.5%) were added and mixed by pipetting gently. Finally, optimized siRNA mixture was printed on 3D hydrogel-coated slides and cell-defined attachment and si

  5. The impact of amino acid variability on alloreactivity defines a functional distance predictive of permissive HLA-DPB1 mismatches in hematopoietic stem cell transplantation.

    PubMed

    Crivello, Pietro; Zito, Laura; Sizzano, Federico; Zino, Elisabetta; Maiers, Martin; Mulder, Arend; Toffalori, Cristina; Naldini, Luigi; Ciceri, Fabio; Vago, Luca; Fleischhauer, Katharina

    2015-02-01

    A major challenge in unrelated hematopoietic stem cell transplantation (HSCT) is the prediction of permissive HLA mismatches, ie, those associated with lower clinical risks compared to their nonpermissive counterparts. For HLA-DPB1, a clinically prognostic model has been shown to be matching for T cell epitope (TCE) groups assigned by cross reactivity of T cells alloreactive to HLA-DPB1∗09:01; however, the molecular basis of this observation is not fully understood. Here, we have mutated amino acids (aa) in 10 positions of HLA-DPB1∗09:01 to other naturally occurring variants, expressed them by lentiviral vectors in B cell lines, and quantitatively measured allorecognition by 17 CD4(+) T cell effectors from 6 unrelated individuals. A significant impact on the median alloresponse was observed for peptide contact positions 9, 11, 35, 55, 69, 76, and 84, but not for positions 8, 56, and 57 pointing away from the groove. A score for the "functional distance" (FD) from HLA-DPB1∗09:01 was defined as the sum of the median impact of polymorphic aa in a given HLA-DPB1 allele on T cell alloreactivity. Established TCE group assignment of 23 alleles correlated with FD scores of ≤0.5, 0.6 to 1.9 and ≥2 for TCE groups 1, 2, and 3, respectively. Based on this, prediction of TCE group assignment will be possible for any given HLA-DPB1 allele, including currently 367 alleles encoding distinct proteins for which T cell cross reactivity patterns are unknown. Experimental confirmation of the in silico TCE group classification was successfully performed for 7 of 7 of these alleles. Our findings have practical implications for the applicability of TCE group matching in unrelated HSCT and provide new insights into the molecular mechanisms underlying this model. The innovative concept of FD opens new potential avenues for risk prediction in unrelated HSCT. PMID:25445022

  6. 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

  7. [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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. Utility of Various Functional and Anatomic Imaging Modalities for Detection of Ectopic Adrenocorticotropin-Secreting Tumors

    PubMed Central

    Zemskova, Marina S.; Gundabolu, Bhaskar; Sinaii, Ninet; Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Chowdhury, Iffat; Gharib, Ahmed M.; Nieman, Lynnette K.

    2010-01-01

    Context: Because ectopic ACTH-secreting (EAS) tumors are often occult, improved imaging is needed. Objective: Our objective was to evaluate the utility of [111In-DTPA-d-Phe]pentetreotide scintigraphy [octreotide (OCT)] imaging at 6 mCi [low OCT (LOCT)] and 18 mCi [high OCT (HOCT)], [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) and [18F]l-3,4-dihydroxyphenylalanine (F-DOPA)-PET scans, computed tomography (CT), and magnetic resonance imaging (MRI). Design and Setting: The study was a prospective evaluation at a clinical research center. Patients: Forty-one subjects participated, 30 (17 female) with resected EAS tumors and 11 (three female) with occult EAS, based on inferior petrosal sinus sampling results and imaging studies. Intervention: Intervention included CT and MRI of neck, chest, abdomen, LOCT (with or without HOCT) and FDG- or F-DOPA-PET without CT every 6–12 months. Main Outcome Measure: Tumor identification was the main outcome measure. Results: Most recent results were analyzed. Eighteen patients had tumor resected on the first visit; otherwise, surgery occurred 33 ± 25 (9–99) months later. Tumor size was 1.9 ± 1.7 (0.8–8.0) cm; 83% were intrathoracic. CT, MRI, LOCT, HOCT, FDG-PET, and F-DOPA-PET had sensitivities per patient of 93% [95% confidence interval (CI) = 79–98%], 90% (95% CI = 74–96%), 57% (95% CI = 39–73%), 50% (95% CI = 25–75%), 64% (95% CI = 35–85%), and 55% (95% CI = 28–79%) and positive predictive values (PPV) per lesion of 66, 74, 79, 89, 53, and 100%, respectively. LOCT and PET detected only lesions seen by CT/MRI; abnormal LOCT or F-DOPA-PET improved PPV of CT/MRI. By modality, the fraction of patients with one or more false-positive findings was 50% by CT, 31% by MRI, 18% by L/HOCT, and 18% by FDG-PET. Eight occult EAS patients had 64 ± 58 (9–198) months follow-up; others had none. Conclusions: High sensitivity and PPV suggest thoracic CT/MRI plus LOCT scans for initial imaging, with lesion

  13. 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

  14. 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

  15. 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

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

    PubMed Central

    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. PMID

  17. 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. PMID:25964753

  18. Utility of EEG measures of brain function in patients with acute stroke.

    PubMed

    Wu, Jennifer; Srinivasan, Ramesh; Burke Quinlan, Erin; Solodkin, Ana; Small, Steven L; Cramer, Steven C

    2016-06-01

    EEG has been used to study acute stroke for decades; however, because of several limitations EEG-based measures rarely inform clinical decision-making in this setting. Recent advances in EEG hardware, recording electrodes, and EEG software could overcome these limitations. The present study examined how well dense-array (256 electrodes) EEG, acquired with a saline-lead net and analyzed with whole brain partial least squares (PLS) modeling, captured extent of acute stroke behavioral deficits and varied in relation to acute brain injury. In 24 patients admitted for acute ischemic stroke, 3 min of resting-state EEG was acquired at bedside, including in the ER and ICU. Traditional quantitative EEG measures (power in a specific lead, in any frequency band) showed a modest association with behavioral deficits [NIH Stroke Scale (NIHSS) score] in bivariate models. However, PLS models of delta or beta power across whole brain correlated strongly with NIHSS score (R(2) = 0.85-0.90) and remained robust when further analyzed with cross-validation models (R(2) = 0.72-0.73). Larger infarct volume was associated with higher delta power, bilaterally; the contralesional findings were not attributable to mass effect, indicating that EEG captures significant information about acute stroke effects not available from MRI. We conclude that 1) dense-array EEG data are feasible as a bedside measure of brain function in patients with acute stroke; 2) high-dimension EEG data are strongly correlated with acute stroke behavioral deficits and are superior to traditional single-lead metrics in this regard; and 3) EEG captures significant information about acute stroke injury not available from structural brain imaging. PMID:26936984

  19. 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

  20. Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function.

    PubMed

    Alberti, Michael O; Jones, Jennifer J; Miglietta, Riccardo; Ding, Haitao; Bakshi, Rakesh K; Edmonds, Tara G; Kappes, John C; Ochsenbauer, Christina

    2015-12-01

    We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a "ribosome skipping" T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models. Herein, we extend our prior work and introduce reporter virus technology for applications that require fully functional Nef. We demonstrate that in CD4(+) T cells productively infected with LucR.T2A reporter viruses, T2A peptide-driven Nef expression and function, such as down-regulation of surface CD4 and MHC-I, were impaired. We overcame this limitation of LucR.T2A reporter viruses and achieved physiological Nef expression and function by engineering novel LucR reporter HIV-1 comprising 11 different internal ribosome entry site (IRES) elements chosen for size and relative activity. A range of Nef expression was observed in 293T cells transfected with the different LucR.IRES reporter virus constructs. Iteratively, we identified IRES reporter genomes that expressed Nef closest to physiological levels and produced virus with infectivity, titers, and replication kinetics similar to nonreporter viruses. Our results demonstrated that LucR reporter activity was stable over multiple replication cycles in peripheral blood mononuclear cells (PBMCs). Furthermore, we analyzed Nef functionality, i.e., down-modulation of MHC-I and CD4, following infection of T cell lines and PBMCs. Unlike LucR.T2A reporter virus, one of the redesigned LucR.IRES reporter viruses [containing the modified encephalomyocarditis virus (EMCV) 6ATR IRES element, "6ATRi"] demonstrated Nef expression and function similar to parental "nonreporter" virus

  1. Cloning, Characterization, and Functional Expression of the Klebsiella oxytoca Xylodextrin Utilization Operon (xynTB) in Escherichia coli†

    PubMed Central

    Qian, Yilei; Yomano, L. P.; Preston, J. F.; Aldrich, H. C.; Ingram, L. O.

    2003-01-01

    Escherichia coli is being developed as a biocatalyst for bulk chemical production from inexpensive carbohydrates derived from lignocellulose. Potential substrates include the soluble xylodextrins (xyloside, xylooligosaccharide) and xylobiose that are produced by treatments designed to expose cellulose for subsequent enzymatic hydrolysis. Adjacent genes encoding xylobiose uptake and hydrolysis were cloned from Klebsiella oxytoca M5A1 and are functionally expressed in ethanologenic E. coli. The xylosidase encoded by xynB contains the COG3507 domain characteristic of glycosyl hydrolase family 43. The xynT gene encodes a membrane protein containing the MelB domain (COG2211) found in Na+/melibiose symporters and related proteins. These two genes form a bicistronic operon that appears to be regulated by xylose (XylR) and by catabolite repression in both K. oxytoca and recombinant E. coli. Homologs of this operon were found in Klebsiella pneumoniae, Lactobacillus lactis, E. coli, Clostridium acetobutylicum, and Bacillus subtilis based on sequence comparisons. Based on similarities in protein sequence, the xynTB genes in K. oxytoca appear to have originated from a gram-positive ancestor related to L. lactis. Functional expression of xynB allowed ethanologenic E. coli to metabolize xylodextrins (xylosides) containing up to six xylose residues without the addition of enzyme supplements. 4-O-methylglucuronic acid substitutions at the nonreducing termini of soluble xylodextrins blocked further degradation by the XynB xylosidase. The rate of xylodextrin utilization by recombinant E. coli was increased when a full-length xynT gene was included with xynB, consistent with xynT functioning as a symport. Hydrolysis rates were inversely related to xylodextrin chain length, with xylobiose as the preferred substrate. Xylodextrins were utilized more rapidly by recombinant E. coli than K. oxytoca M5A1 (the source of xynT and xynB). XynB exhibited weak arabinosidase activity, 3% that of

  2. 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. PMID:26754423

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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. PMID:25875447

  8. The HCV non-nucleoside inhibitor Tegobuvir utilizes a novel mechanism of action to inhibit NS5B polymerase function.

    PubMed

    Hebner, Christy M; Han, Bin; Brendza, Katherine M; Nash, Michelle; Sulfab, Maisoun; Tian, Yang; Hung, Magdeleine; Fung, Wanchi; Vivian, Randall W; Trenkle, James; Taylor, James; Bjornson, Kyla; Bondy, Steven; Liu, Xiaohong; Link, John; Neyts, Johan; Sakowicz, Roman; Zhong, Weidong; Tang, Hengli; Schmitz, Uli

    2012-01-01

    Tegobuvir (TGV) is a novel non-nucleoside inhibitor (NNI) of HCV RNA replication with demonstrated antiviral activity in patients with genotype 1 chronic HCV infection. The mechanism of action of TGV has not been clearly defined despite the identification of resistance mutations mapping to the NS5B polymerase region. TGV does not inhibit NS5B enzymatic activity in biochemical assays in vitro, suggesting a more complex antiviral mechanism with cellular components. Here, we demonstrate that TGV exerts anti-HCV activity utilizing a unique chemical activation and subsequent direct interaction with the NS5B protein. Treatment of HCV subgenomic replicon cells with TGV results in a modified form of NS5B with a distinctly altered mobility on a SDS-PAGE gel. Further analysis reveals that the aberrantly migrating NS5B species contains the inhibitor molecule. Formation of this complex does not require the presence of any other HCV proteins. The intensity of the aberrantly migrating NS5B species is strongly dependent on cellular glutathione levels as well as CYP 1A activity. Furthermore analysis of NS5B protein purified from a heterologous expression system treated with TGV by mass spectrometry suggests that TGV undergoes a CYP- mediated intracellular activation step and the resulting metabolite, after forming a glutathione conjugate, directly and specifically interacts with NS5B. Taken together, these data demonstrate that upon metabolic activation TGV is a specific, covalent inhibitor of the HCV NS5B polymerase and is mechanistically distinct from other classes of the non-nucleoside inhibitors (NNI) of the viral polymerase. PMID:22720059

  9. Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function.

    PubMed Central

    Aroian, R V; Lesa, G M; Sternberg, P W

    1994-01-01

    The Caenorhabditis elegans let-23 gene is a genetically characterized member of the epidermal growth factor receptor (EGFR) tyrosine kinase family. Mutations in let-23 can produce five phenotypes in the nematode. Alleles of let-23 include null alleles, reduction-of-function alleles and alleles that disrupt function in some cell types and not others. We have sequenced some of these mutations to identify sequences and regions important for overall let-23 function and for let-23 function in specific cell types. Our data indicate that in vivo, the receptor's C-terminus can be partitioned into at least three domains that each contribute to receptor function in different cell types. In particular, we find distinct domains that mediate hermaphrodite fertility and vulval induction. Our data also demonstrate for the first time that a single, conserved residue in the ligand binding domain is critical for function in vivo and that mutations in the extracellular cysteines characteristic of the EGFR family can lead to a partial or a complete reduction of receptor function. Images PMID:8313880

  10. 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.

  11. 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.

  12. 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

  13. Distribution and Functions of TonB-Dependent Transporters in Marine Bacteria and Environments: Implications for Dissolved Organic Matter Utilization

    PubMed Central

    Tang, Kai; Jiao, Nianzhi; Liu, Keshao; Zhang, Yao; Li, Shuhui

    2012-01-01

    Background Bacteria play critical roles in marine nutrient cycles by incorporating and redistributing dissolved organic matter (DOM) and inorganic nutrients in the ocean. TonB-dependent transporter (TBDT) proteins allow Gram-negative bacteria to take up scarce resources from nutrient-limiting environments as well as siderophores, heme, vitamin B12, and recently identified carbohydrates. Thus, the characterization of TBDT distribution and functions is essential to better understand the contribution TBDT to DOM assimilation and its consequences on nutrient cycling in the environment. Methodology/Principal Findings This study presents the distribution of encoded known and putative TBDT proteins in the genomes of microorganisms and from the Global Ocean Survey data. Using a Lek clustering algorithm and substrate specificities, the TBDT sequences were mainly classified into the following three groups: (1) DOM transporters; (2) Siderophores/Vitamins transporters; and (3) Heme/Hemophores/Iron(heme)-binding protein transporters. Diverse TBDTs were found in the genomes of oligotroph Citromicrobium bathyomarinum JL354 and Citromicrobium sp JLT1363 and were highly expressed in the stationary phase of bacterial growth. The results show that the Gammaproteobacteria and the Cytophaga-Flavobacterium-Bacteroides (CFB) group bacteria accounted for the majority of the TBDT gene pool in marine surface waters. Conclusions/Significance The results of this study confirm the ecological importance of TBDTs in DOM assimilation for bacteria in marine environments owing to a wide range of substrate utilization potential in the ubiquitous Gammaproteobacteria and CFB group bacteria. PMID:22829928

  14. Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.

    PubMed

    Burkard, Lexi; Scheuermann, Alexis; Simithy, Johayra; Calderón, Angela I

    2016-04-01

    Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth. In addition, it has been confirmed that PfGR is not identical to human GR. Thus, PfGR is an excellent target for antimalarial drug development. A functional assay utilizing liquid chromatography-mass spectrometry was developed to specifically identify and evaluate inhibitors of PfGR. Using recombinant PfGR enzyme and 1,4-naphthoquinone (1) as a reference compound and 4-nitrobenzothiadiazole (2) and methylene blue (3) as additional compounds, we quantified the concentration of GSH produced compared with a control to determine the inhibitory effect of these compounds. Our results coincide with that presented in literature: compounds 1-3 inhibit PfGR with IC50 values of 2.71, 8.38, and 19.23 µm, respectively. Good precision for this assay was exhibited by low values of intraday and interday coefficient of variation (3.1 and 2.4%, respectively). Thus, this assay can be used to screen for other potential inhibitors of PfGR quickly and accurately. PMID:26257195

  15. Sca-1 expression defines developmental stages of mouse pDCs that show functional heterogeneity in the endosomal but not lysosomal TLR9 response.

    PubMed

    Niederquell, Marina; Kurig, Stefanie; Fischer, Jens A A; Tomiuk, Stefan; Swiecki, Melissa; Colonna, Marco; Johnston, Ian C D; Dzionek, Andrzej

    2013-11-01

    Plasmacytoid dendritic cells (pDCs) play an important role in innate and adaptive immunity and were shown to be identical to previously described natural interferon (IFN)-α-producing cells. Here, we describe two functionally distinct pDC subpopulations that are characterized by the differential expression of stem cell antigen-1 (Sca-1; Ly-6A/E). Sca-1(-) pDCs are mainly found in the BM, appear first during development, show a higher proliferative activity, and represent the more precursor phenotype. Sca-1(+) pDCs are mostly located in secondary lymphoid organs and represent a later developmental stage. Sca-1(-) pDCs give rise to an Sca-1(+) subset upon activation or in response to endogenous type I IFN. Interestingly, in contrast to Sca-1(-) pDCs, Sca-1(+) pDCs are defective in IFN-α production upon endosomal TLR9 stimulation, whereas lysosomal signaling via TLR9 is functional in both subsets. Gene expression analysis revealed that osteopontin is strongly upregulated in Sca-1(-) pDCs. These data provide evidence for the molecular basis of the observed functional heterogeneity, as the intracellular isoform of osteopontin couples TLR9 signaling to IFN-α expression. Taken together, our results indicate that Sca-1(-) pDCs are an early developmental stage of pDCs with distinct innate functions representing the true murine natural IFN-α-producing cells. PMID:23922217

  16. 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

  17. 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

  18. 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

  19. Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain

    PubMed Central

    Hauptrock, Beate; Malina, Victoria; Antunes, Edite; Voss, Ralf-Holger; Wolfl, Matthias; Strong, Roland; Theobald, Matthias; Greenberg, Philip D.

    2009-01-01

    Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to impart tumor reactivity has been reported as a potential strategy to redirect immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev. Immunol. 2:512–519). However, the affinity of most TCRs specific for shared tumor antigens that can be isolated is usually low. Thus, strategies to increase the affinity of TCRs or the functional avidity of TCR-transduced T cells might be therapeutically beneficial. Because glycosylation affects the flexibility, movement, and interactions of surface molecules, we tested if selectively removing conserved N-glycoslyation sites in the constant regions of TCR α or β chains could increase the functional avidity of T cells transduced with such modified TCRs. We observed enhanced functional avidity and improved recognition of tumor cells by T cells harboring TCR chains with reduced N-glycosylation (ΔTCR) as compared with T cells with wild-type (WT) TCR chains. T cells transduced with WT or ΔTCR chains bound tetramer equivalently at 4°C, but tetramer binding was enhanced at 37°C, predominantly as a result of reduced tetramer dissociation. This suggested a temperature-dependent mechanism such as TCR movement in the cell surface or structural changes of the TCR allowing improved multimerization. This strategy was effective with mouse and human TCRs specific for different antigens and, thus, should be readily translated to TCRs with any specificity. PMID:19171765

  20. Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus.

    PubMed

    Forsberg, Zarah; Nelson, Cassandra E; Dalhus, Bjørn; Mekasha, Sophanit; Loose, Jennifer S M; Crouch, Lucy I; Røhr, Åsmund K; Gardner, Jeffrey G; Eijsink, Vincent G H; Vaaje-Kolstad, Gustav

    2016-04-01

    Cellvibrio japonicusis a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin-degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO,CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of theCjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both α- and β-chitin. Removal of the chitin-binding modules reduced LPMO activity toward α-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show thatCjLPMO10A is needed byC. japonicusto obtain efficient growth on both purified chitin and crab shell particles. PMID:26858252

  1. Japanese plan for SSF utilization

    NASA Technical Reports Server (NTRS)

    Mizuno, Toshio

    1992-01-01

    The Japanese Experiment Module (JEM) program has made significant progress. The JEM preliminary design review was completed in July 1992; construction of JEM operation facilities has begun; and the micro-G airplane, drop shaft, and micro-G experiment rocket are all operational. The national policy for JEM utilization was also established. The Space Experiment Laboratory (SEL) opened in June '92 and will function as a user support center. Eight JEM multiuser facilities are in phase B, and scientific requirements are being defined for 17 candidate multiuser facilities. The National Joint Research Program is about to start. Precursor missions and early Space Station utilization activities are being defined. This paper summarizes the program in outline and graphic form.

  2. The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits*

    PubMed Central

    Homma, Kazuaki; Duan, Chongwen; Zheng, Jing; Cheatham, Mary Ann; Dallos, Peter

    2013-01-01

    Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer. PMID:23212912

  3. 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

  4. WW domains of Rsp5p define different functions: determination of roles in fluid phase and uracil permease endocytosis in Saccharomyces cerevisiae.

    PubMed

    Gajewska, B; Kamińska, J; Jesionowska, A; Martin, N C; Hopper, A K; Zoładek, T

    2001-01-01

    Rsp5p, ubiquitin-protein ligase, an enzyme of the ubiquitination pathway, contains three WW domains that mediate protein-protein interactions. To determine if these domains adapt Rsp5p to a subset of substrates involved in numerous cellular processes, we generated mutations in individual or combinations of the WW domains. The rsp5-w1, rsp5-w2, and rsp5-w3 mutant alleles complement RSP5 deletions at 30 degrees. Thus, individual WW domains are not essential. Each rsp5-w mutation caused temperature-sensitive growth. Among variants with mutations in multiple WW domains, only rsp5-w1w2 complemented the deletion. Thus, the WW3 domain is sufficient for Rsp5p essential functions. To determine whether rsp5-w mutations affect endocytosis, fluid phase and uracil permease (Fur4p) endocytosis was examined. The WW3 domain is important for both processes. WW2 appears not to be important for fluid phase endocytosis whereas it is important for Fur4p endocytosis. In contrast, the WW1 domain affects fluid phase endocytosis, but it does not appear to function in Fur4p endocytosis. Thus, various WW domains play different roles in the endocytosis of these two substrates. Rsp5p is located in the cytoplasm in a punctate pattern that does not change during the cell cycle. Altering WW domains does not change the location of Rsp5p. PMID:11139494

  5. 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

  6. In vivo genetic mutations define predominant functions of the human T-cell leukemia/lymphoma virus p12I protein

    PubMed Central

    Fukumoto, Risaku; Andresen, Vibeke; Bialuk, Izabela; Cecchinato, Valentina; Walser, Jean-Claude; Valeri, Valerio W.; Nauroth, Julie M.; Gessain, Antoine; Nicot, Christophe

    2009-01-01

    The human T-cell leukemia/lymphoma virus type 1 (HTLV-1) ORF-I encodes a 99–amino acid hydrophobic membrane protein, p12I, that affects receptors in different cellular compartments. We report here that proteolytic cleavage dictates different cellular localization and functions of p12I. The removal of a noncanonical endoplasmic reticulum (ER) retention/retrieval signal within the amino terminus of p12I is necessary for trafficking to the Golgi apparatus and generation of a completely cleaved 8-kDa protein. The 8-kDa protein in turn traffics to the cell surface, is recruited to the immunologic synapse following T-cell receptor (TCR) ligation, and down-regulates TCR proximal signaling. The uncleaved 12-kDa form of p12I resides in the ER and interacts with the β and γc chains of the interleukin-2 receptor (IL-2R), the heavy chain of the major histocompatibility complex (MHC) class I, as well as calreticulin and calnexin. Genetic analysis of ORF-I from ex vivo samples of HTLV-1–infected patients reveals predominant amino acid substitutions within ORF-I that affect proteolytic cleavage, suggesting that ER-associated functions of p12I may contribute to the survival and proliferation of the infected T cells in the host. PMID:18791162

  7. 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

  8. 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.

  9. 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

    2013-07-01

    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

  10. Defining how aging Pseudotsuga and Abies compensate for multiple stresses through multi-criteria assessment of a functional-structural model.

    PubMed

    Kennedy, Maureen C; Ford, E David; Hinckley, Thomas M

    2010-01-01

    Many hypotheses have been advanced about factors that control tree longevity. We use a simulation model with multi-criteria optimization and Pareto optimality to determine branch morphologies in the Pinaceae that minimize the effect of growth limitations due to water stress while simultaneously maximizing carbohydrate gain. Two distinct branch morphologies in the Pareto optimal space resemble Pseudotsuga menziesii (Mirb.) Franco and Abies grandis (Dougl. ex D. Don) Lindl., respectively. These morphologies are distinguished by their performance with respect to two pathways of compensation for hydraulic limitation: minimizing the mean path length to terminal foliage (Pseudotsuga) and minimizing the mean number of junction constrictions to terminal foliage (Abies). Within these two groups, we find trade-offs between the criteria for foliage display and the criteria for hydraulic functioning, which shows that an appropriate framework for considering tree longevity is how trees compensate, simultaneously, for multiple stresses. The diverse morphologies that are found in a typical old-growth conifer forest may achieve compensation in different ways. The method of Pareto optimization that we employ preserves all solutions that are successful in achieving different combinations of criteria. The model for branch development that we use simulates the process of delayed adaptive reiteration (DAR), whereby new foliage grows from suppressed buds within the established branch structure. We propose a theoretical synthesis for the role of morphology in the persistence of old Pseudotsuga based on the characteristics of branch morphogenesis found in branches simulated from the optimal set. (i) The primary constraint on branch growth for Pseudotsuga is the mean path length; (ii) as has been previously noted, DAR is an opportunistic architecture; and (iii) DAR is limited by the number of successive reiterations that can form. We show that Pseudotsuga morphology is not the only

  11. 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

  12. Functional characterization of a higher plant sphingolipid Delta4-desaturase: defining the role of sphingosine and sphingosine-1-phosphate in Arabidopsis.

    PubMed

    Michaelson, Louise V; Zäuner, Simone; Markham, Jonathan E; Haslam, Richard P; Desikan, Radhika; Mugford, Sarah; Albrecht, Sandra; Warnecke, Dirk; Sperling, Petra; Heinz, E; Napier, Johnathan A

    2009-01-01

    The role of Delta4-unsaturated sphingolipid long-chain bases such as sphingosine was investigated in Arabidopsis (Arabidopsis thaliana). Identification and functional characterization of the sole Arabidopsis ortholog of the sphingolipid Delta4-desaturase was achieved by heterologous expression in Pichia pastoris. A P. pastoris mutant disrupted in the endogenous sphingolipid Delta4-desaturase gene was unable to synthesize glucosylceramides. Synthesis of glucosylceramides was restored by the expression of Arabidopsis gene At4g04930, and these sphingolipids were shown to contain Delta4-unsaturated long-chain bases, confirming that this open reading frame encodes the sphingolipid Delta4-desaturase. At4g04930 has a very restricted expression pattern, transcripts only being detected in pollen and floral tissues. Arabidopsis insertion mutants disrupted in the sphingolipid Delta4-desaturase At4g04930 were isolated and found to be phenotypically normal. Sphingolipidomic profiling of a T-DNA insertion mutant indicated the absence of Delta4-unsaturated sphingolipids in floral tissue, also resulting in the reduced accumulation of glucosylceramides. No difference in the response to drought or water loss was observed between wild-type plants and insertion mutants disrupted in the sphingolipid Delta4-desaturase At4g04930, nor was any difference observed in stomatal closure after treatment with abscisic acid. No differences in pollen viability between wild-type plants and insertion mutants were detected. Based on these observations, it seems unlikely that Delta4-unsaturated sphingolipids and their metabolites such as sphingosine-1-phosphate play a significant role in Arabidopsis growth and development. However, Delta4-unsaturated ceramides may play a previously unrecognized role in the channeling of substrates for the synthesis of glucosylceramides. PMID:18978071

  13. Functional Characterization of a Higher Plant Sphingolipid Δ4-Desaturase: Defining the Role of Sphingosine and Sphingosine-1-Phosphate in Arabidopsis1[W][OA

    PubMed Central

    Michaelson, Louise V.; Zäuner, Simone; Markham, Jonathan E.; Haslam, Richard P.; Desikan, Radhika; Mugford, Sarah; Albrecht, Sandra; Warnecke, Dirk; Sperling, Petra; Heinz, E.; Napier, Johnathan A.

    2009-01-01

    The role of Δ4-unsaturated sphingolipid long-chain bases such as sphingosine was investigated in Arabidopsis (Arabidopsis thaliana). Identification and functional characterization of the sole Arabidopsis ortholog of the sphingolipid Δ4-desaturase was achieved by heterologous expression in Pichia pastoris. A P. pastoris mutant disrupted in the endogenous sphingolipid Δ4-desaturase gene was unable to synthesize glucosylceramides. Synthesis of glucosylceramides was restored by the expression of Arabidopsis gene At4g04930, and these sphingolipids were shown to contain Δ4-unsaturated long-chain bases, confirming that this open reading frame encodes the sphingolipid Δ4-desaturase. At4g04930 has a very restricted expression pattern, transcripts only being detected in pollen and floral tissues. Arabidopsis insertion mutants disrupted in the sphingolipid Δ4-desaturase At4g04930 were isolated and found to be phenotypically normal. Sphingolipidomic profiling of a T-DNA insertion mutant indicated the absence of Δ4-unsaturated sphingolipids in floral tissue, also resulting in the reduced accumulation of glucosylceramides. No difference in the response to drought or water loss was observed between wild-type plants and insertion mutants disrupted in the sphingolipid Δ4-desaturase At4g04930, nor was any difference observed in stomatal closure after treatment with abscisic acid. No differences in pollen viability between wild-type plants and insertion mutants were detected. Based on these observations, it seems unlikely that Δ4-unsaturated sphingolipids and their metabolites such as sphingosine-1-phosphate play a significant role in Arabidopsis growth and development. However, Δ4-unsaturated ceramides may play a previously unrecognized role in the channeling of substrates for the synthesis of glucosylceramides. PMID:18978071

  14. 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

  15. 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

  16. 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 ...

  17. Interpolation and Definability

    NASA Astrophysics Data System (ADS)

    Gabbay, Dov M.; Maksimova, Larisa L.

    This chapter is on interpolation and definability. This notion is not only central in pure logic, but has significant meaning and applicability in all areas where logic itself is applied, especially in computer science, artificial intelligence, logic programming, philosophy of science and natural language. The notion may sometimes appear to the reader as too technical/mathematical but it does also have a general meaning in terms of expressibility and definability.

  18. 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...

  19. Molecularly defined antibody conjugation through a selenocysteine interface†

    PubMed Central

    Hofer, Thomas; Skeffington, Lauren R.; Chapman, Colby M.; Rader, Christoph

    2009-01-01

    Antibody conjugates have broad utility in basic, preclinical, and clinical applications. Conventional antibody conjugation through the amine group of lysine or the thiol group of cysteine residues yields heterogeneous products of undefined stoichiometry and considerable batch-to-batch variability. To preserve the two hallmarks of the antibody molecule, precision and predictability, methods that enable site-specific antibody conjugation are in high demand. Based on a mammalian cell expression system, we describe the utilization of the 21st natural amino acid selenocysteine for the generation of IgG and Fab molecules with unique nucleophilic reactivity that affords site-specific conjugation to electrophilic derivatives of biotin, fluorescein, and poly(ethylene glycol). The resulting antibody conjugates were found to fully retain their antigen binding capability and, in case of IgG, the ability to mediate effector functions. Gain-of-function was demonstrated in vitro and in vivo. While these antibody conjugates are relevant for a variety of proteomic, diagnostic, and therapeutic applications, they also constitute a proof-of-principle for the generation of molecularly defined antibody-drug conjugates and radioimmunoconjugates. Compared to other site-specific antibody conjugation methods, selenocysteine interface technology (i) only involves a minor modification at the C-terminus that does not interfere with disulfide bridges, (ii) does not require activation, and (iii) generates unique 1:1 stoichiometries of biological and chemical component. Collectively, our method affords the generation of highly defined antibody conjugates with broad utility from proteomic applications to therapeutic intervention. PMID:19894757

  20. Defining nodes in complex brain networks

    PubMed Central

    Stanley, Matthew L.; Moussa, Malaak N.; Paolini, Brielle M.; Lyday, Robert G.; Burdette, Jonathan H.; Laurienti, Paul J.

    2013-01-01

    Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel). The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10–20 millimeter diameter) spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the “correct” method to be used remains an open, possibly unsolvable question that deserves

  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 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…

  3. Defining Supports Geometry

    ERIC Educational Resources Information Center

    Stephan, Michelle L.; McManus, George E.; Dickey, Ashley L.; Arb, Maxwell S.

    2012-01-01

    The process of developing definitions is underemphasized in most mathematics instruction. Investing time in constructing meaning is well worth the return in terms of the knowledge it imparts. In this article, the authors present a third approach to "defining," called "constructive." It involves modifying students' previous understanding of a term…

  4. 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…

  5. 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…

  6. 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…

  7. Defining structural limit zones

    NASA Technical Reports Server (NTRS)

    Merchant, D. H.

    1978-01-01

    Method for defining limit loads uses probability distribution of largest load occurring during given time intervals. Method is compatible with both deterministic and probabilistic structural design criteria. It also rationally accounts for fact that longer structure is exposed to random loading environment, greater is possibility that it will experience extreme load.

  8. Defining Airflow Obstruction

    PubMed Central

    Eschenbacher, William L.

    2016-01-01

    Airflow obstruction has been defined using spirometric test results when the forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio is below a fixed cutoff (<70%) or lower limits of normal (LLN) from reference equations that are based on values from a normal population. However, similar to other positive or abnormal diagnostic test results that are used to identify the presence of disease, perhaps airflow obstruction should be defined based on the values of FEV1/FVC for a population of individuals with known disease such as chronic obstructive pulmonary disease (COPD). Unfortunately, we do not know such a distribution of values of FEV1/FVC for patients with COPD since there is no gold standard for this syndrome or condition. Yet, we have used this physiologic definition of airflow obstruction based on a normal population to identify patients with COPD. In addition, we have defined airflow obstruction as either being present or absent. Instead, we should use a different approach to define airflow obstruction based on the probability or likelihood that the airflow obstruction is present which in turn would give us the probability or likelihood of a disease state such as COPD. PMID:27239557

  9. 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.

  10. 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…

  11. Both Loss-of-Function and Gain-of-Function Mutations in Snf Define a Role for Snrnp Proteins in Regulating Sex-Lethal Pre-mRNA Splicing in Drosophila Development

    PubMed Central

    Salz, H. K.; Flickinger, T. W.

    1996-01-01

    The Drosophila snf gene encodes a protein with functional homology to the mammalian U1A and U2B" snRNP proteins. Studies, based on the analysis of three viable alleles, have suggested a role for snf in establishing the female-specific splicing pattern of the sex determination switch gene, Sex-lethal. Here, we show that the non-sex-specific lethal null allele is required for female sex determination, arguing against the formal possibility that the viable alleles disrupt a function unrelated to snf's wild-type function. Moreover, we find snf is required for normal cell growth and/or survival, as expected for a protein involved in a cell-vital process such as RNA splicing. We also show that of the three viable alleles only one, snf(JA2), is a partial loss-of-function mutation. The other two viable alleles, snf(1621) and snf(e8H), encode antimorphic proteins. We find the antimorphic proteins are mislocalized and correlate their mislocalization with their molecular lesions and mutant phenotypes. Finally, we provide genetic evidence that the antimorphic alleles interfere with the autoregulatory splicing function of the Sex-lethal protein. Based on these studies we suggest a model in which the snRNP protein, Snf, functions with Sex-lethal to block recognition of the regulated male-specific exon. PMID:8878676

  12. Defining Dynamic Route Structure

    NASA Technical Reports Server (NTRS)

    Zelinski, Shannon; Jastrzebski, Michael

    2011-01-01

    This poster describes a method for defining route structure from flight tracks. Dynamically generated route structures could be useful in guiding dynamic airspace configuration and helping controllers retain situational awareness under dynamically changing traffic conditions. Individual merge and diverge intersections between pairs of flights are identified, clustered, and grouped into nodes of a route structure network. Links are placed between nodes to represent major traffic flows. A parametric analysis determined the algorithm input parameters producing route structures of current day flight plans that are closest to todays airway structure. These parameters are then used to define and analyze the dynamic route structure over the course of a day for current day flight paths. Route structures are also compared between current day flight paths and more user preferred paths such as great circle and weather avoidance routing.

  13. Defining the paramedic process.

    PubMed

    Carter, Holly; Thompson, James

    2015-01-01

    The use of a 'process of care' is well established in several health professions, most evidently within the field of nursing. Now ingrained within methods of care delivery, it offers a logical approach to problem solving and ensures an appropriate delivery of interventions that are specifically suited to the individual patient. Paramedicine is a rapidly advancing profession despite a wide acknowledgement of limited research provisions. This frequently results in the borrowing of evidence from other disciplines. While this has often been useful, there are many concerns relating to the acceptable limit of evidence transcription between professions. To date, there is no formally recognised 'process of care'-defining activity within the pre-hospital arena. With much current focus on the professional classification of paramedic work, it is considered timely to formally define a formula that underpins other professional roles such as nursing. It is hypothesised that defined processes of care, particularly the nursing process, may have features that would readily translate to pre-hospital practice. The literature analysed was obtained through systematic searches of a range of databases, including Ovid MEDLINE, Cumulative Index to Nursing and Allied Health. The results demonstrated that the defined process of care provides nursing with more than just a structure for practice, but also has implications for education, clinical governance and professional standing. The current nursing process does not directly articulate to the complex and often unstructured role of the paramedic; however, it has many principles that offer value to the paramedic in their practice. Expanding the nursing process model to include the stages of Dispatch Considerations, Scene Assessment, First Impressions, Patient History, Physical Examination, Clinical Decision-Making, Interventions, Re-evaluation, Transport Decisions, Handover and Reflection would provide an appropriate model for pre

  14. 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.

  15. 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

  16. Functional analysis and regulation of the divergent spuABCDEFGH-spuI operons for polyamine uptake and utilization in Pseudomonas aeruginosa PAO1.

    PubMed

    Lu, Chung-Dar; Itoh, Yoshifumi; Nakada, Yuji; Jiang, Ying

    2002-07-01

    A multiple-gene locus for polyamine uptake and utilization was discovered in Pseudomonas aeruginosa PAO1. This locus contained nine genes designated spuABCDEFGHI (spu for spermidine and putrescine utilization). The physiological functions of the spu genes in utilization of two polyamines (putrescine and spermidine) were analyzed by using Tn5 transposon-mediated spu knockout mutants. Growth and uptake experiments support that the spuDEFGH genes specify components of a major ABC-type transport system for spermidine uptake, and enzymatic measurements indicated that spuC encodes putrescine aminotransferase with pyruvate as the amino group receptor. Although spuA and spuB mutants showed an apparent defect in spermidine utilization, the biochemical functions of the gene products have yet to be elucidated. Assays of lacZ fusions demonstrated the presence of agmatine-, putrescine-, and spermidine-inducible promoters for the spuABCDEFGH operon and the divergently transcribed spuI gene of unknown function. Since the observed induction effect of agmatine was abolished in an aguA mutant where conversion of agmatine into putrescine was blocked, putrescine or spermidine, but not agmatine, serves as the inducer molecule of the spuA-spuI divergent promoters. S1 nuclease mappings confirmed further the induction effects of the polyamines on transcription of the divergent promoters and localized the transcription initiation sites. Gel retardation assays with extracts from the cells grown on putrescine or spermidine demonstrated the presence of a polyamine-responsive regulatory protein interacting with the divergent promoter region. Finally, the absence of the putrescine-inducible spuA expression and putrescine aminotransferase (spuC) formation in the cbrB mutant indicated that the spu operons are regulated by the global CbrAB two-component system perhaps via the putative polyamine-responsive transcriptional activator. PMID:12081945

  17. 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.

  18. 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.

  19. 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

  20. Quantum Dynamics with Gaussian Bases Defined by the Quantum Trajectories.

    PubMed

    Gu, Bing; Garashchuk, Sophya

    2016-05-19

    Development of a general approach to construction of efficient high-dimensional bases is an outstanding challenge in quantum dynamics describing large amplitude motion of molecules and fragments. A number of approaches, proposed over the years, utilize Gaussian bases whose parameters are somehow-usually by propagating classical trajectories or by solving coupled variational equations-tailored to the shape of a wave function evolving in time. In this paper we define the time-dependent Gaussian bases through an ensemble of quantum or Bohmian trajectories, known to provide a very compact representation of a wave function due to conservation of the probability density associated with each trajectory. Though the exact numerical implementation of the quantum trajectory dynamics itself is, generally, impractical, the quantum trajectories can be obtained from the wave function expanded in a basis. The resulting trajectories are used to guide compact Gaussian bases, as illustrated on several model problems. PMID:26735750

  1. What can water utilities do to improve risk management within their business functions? An improved tool and application of process benchmarking.

    PubMed

    MacGillivray, Brian H; Pollard, Simon J T

    2008-11-01

    We present a model for benchmarking risk analysis and risk based decision making practice within organisations. It draws on behavioural and normative risk research, the principles of capability maturity modelling and our empirical observations. It codifies the processes of risk analysis and risk based decision making within a framework that distinguishes between different levels of maturity. Application of the model is detailed within the selected business functions of a water and wastewater utility. Observed risk analysis and risk based decision making practices are discussed, together with their maturity of implementation. The findings provide academics, utility professionals, and regulators a deeper understanding of the practical and theoretical underpinnings of risk management, and how distinctions can be made between organisational capabilities in this essential business process. PMID:18554718

  2. 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...

  3. Improved gut barrier function via increased threonine utilization may explain enhanced resistance to necrotizing enterocolitis in preterm pigs fed colostrum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Threonine is an essential amino acid necessary for synthesis of gut mucins that form the protective intestinal mucous layer. In premature infants, this function might be compromised leading to necrotizing enterocolitis (NEC). We hypothesized that enteral feeding with colostrum, relative to infant fo...

  4. The clinical utility and specificity of parent report of executive function among children with prenatal alcohol exposure.

    PubMed

    Nguyen, Tanya T; Glass, Leila; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-08-01

    Prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8-16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE-, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure. PMID:25033032

  5. 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

  6. In situ characterization of antigenic and functional tissue factor expression in human tumors utilizing monoclonal antibodies and recombinant factor VIIa as probes.

    PubMed Central

    Contrino, J.; Hair, G. A.; Schmeizl, M. A.; Rickles, F. R.; Kreutzer, D. L.

    1994-01-01

    Tissue factor (TF), the primary initiator of blood coagulation in vivo, is expressed in vitro by a variety of cells. Previous efforts to localize TF in tissue and cells have been limited principally to the use of immunological techniques. In the present study, we describe a novel functional probe for TF expression, which can be utilized to localize functional TF in situ in human cells and tissues. This probe, a biotinylated phe-pro-arg-chloro-methyl-ketone-labeled rVIIa (FPR-ck-VIIa), interacts with TF via high-affinity binding sites. The binding of FPR-ck-VIIa, therefore, can be correlated with the ability of TF to activate clotting. In the described studies, TF antigen (TF:Ag) expression was examined immunohistochemically with various TF-specific monoclonal antibodies (MAbs) and was correlated with functional TF expression using our novel TF-binding probe (eg, FPR-ck-VIIa). Initial results indicate that TF:Ag expression correlates with the expression of functional TF (TF:VIIa), and the specificity of both types of probes was confirmed. Parallel antigenic and functional TF expression in situ was demonstrated in various human tumors. We believe this to be the first demonstration of functional TF in situ in human cells and tissues. We suggest that FPR-ck-VIIa should prove a useful reagent for studying the role of TF in the pathogenesis of clotting complications of human disease. Images Figure 1 Figure 2 Figure 4 PMID:7992837

  7. 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.

  8. A Toolbox of Diverse Promoters Related to Methanol Utilization: Functionally Verified Parts for Heterologous Pathway Expression in Pichia pastoris.

    PubMed

    Vogl, Thomas; Sturmberger, Lukas; Kickenweiz, Thomas; Wasmayer, Richard; Schmid, Christian; Hatzl, Anna-Maria; Gerstmann, Michaela A; Pitzer, Julia; Wagner, Marlies; Thallinger, Gerhard G; Geier, Martina; Glieder, Anton

    2016-02-19

    The heterologous expression of biosynthetic pathways for pharmaceutical or fine chemical production requires suitable expression hosts and vectors. In eukaryotes, the pathway flux is typically balanced by stoichiometric fine-tuning of reaction steps by varying the transcript levels of the genes involved. Regulated (inducible) promoters are desirable to allow a separation of pathway expression from cell growth. Ideally, the promoter sequences used should not be identical to avoid loss by recombination. The methylotrophic yeast Pichia pastoris is a commonly used protein production host, and single genes have been expressed at high levels using the methanol-inducible, strong, and tightly regulated promoter of the alcohol oxidase 1 gene (PAOX1). Here, we have studied the regulation of the P. pastoris methanol utilization (MUT) pathway to identify a useful set of promoters that (i) allow high coexpression and (ii) differ in DNA sequence to increase genetic stability. We noticed a pronounced involvement of the pentose phosphate pathway (PPP) and genes involved in the defense of reactive oxygen species (ROS), providing strong promoters that, in part, even outperform PAOX1 and offer novel regulatory profiles. We have applied these tightly regulated promoters together with novel terminators as useful tools for the expression of a heterologous biosynthetic pathway. With the synthetic biology toolbox presented here, P. pastoris is now equipped with one of the largest sets of strong and co-regulated promoters of any microbe, moving it from a protein production host to a general industrial biotechnology host. PMID:26592304

  9. Utility of biological membranes as indicators for radiation exposure: alterations in membrane structure and function over time.

    PubMed

    Dainiak, N; Tan, B J

    1995-05-01

    In addition to interacting with genomic DNA, ionizing radiation may directly and indirectly alter the structure and function of components of the plasma membrane of eukaryotic cells. Water radiolysis generates reactive species, including superoxide, hypochlorous acid and chloride radicals that may in turn react with biological membranes, as well as with cellular DNA. Reaction of plasma membrane lipids with molecular oxygen results in lipid peroxidation of both reconstituted membranes and biological membranes, an effect that increases with decreasing dose rate. Both ionizing radiation and ultraviolet light alter functions of membrane-anchored molecules, including adhesion molecules, histocompatibility complex antigens and membrane-bound growth factors. The latter growth factors represent a repertoire of growth and differentiation signals that are expressed in a nondiffusible fashion at the cell surface, and in soluble forms appearing after cleavage of their extracellular domain. The importance of cell-cell signaling via the membrane-anchored form of growth factors is becoming increasingly recognized. Expression of membrane-bound hematopoietic cytokines by eukaryotic cells is impaired after exposure to ultraviolet light, a defect in cell-cell signaling that may lead to impaired hematopoiesis. While studies suggest that permanent changes in membrane structure and function may result from radiation-induced injury to the plasma membrane and reconstituted "pure" membranes, reversibility of these defects over time requires additional study. PMID:7488940

  10. Implant/tooth-connected restorations utilizing screw-fixed attachments: a survey of 3,096 sites in function for 3 to 14 years.

    PubMed

    Fugazzotto, P A; Kirsch, A; Ackermann, K L; Neuendorff, G

    1999-01-01

    Numerous problems have been reported following various therapies used to attach natural teeth to implants beneath a fixed prosthesis. This study documents the results of 843 consecutive patients treated with 1,206 natural tooth/implant-supported prostheses utilizing 3,096 screw-fixed attachments. After 3 to 14 years in function, only 9 intrusion problems were noted. All problems were associated with fractured or lost screws. This report demonstrates the efficacy of such a treatment approach when a natural tooth/implant-supported fixed prosthesis is contemplated. PMID:10612918

  11. 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

  12. 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.

  13. 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

  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. 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

  16. 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

  17. 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

  18. 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.

  19. 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. PMID:11996584

  20. Utilizing Functionalized Nano-Paterned Surfaces as a clue to Cell Metastasis in Prostate and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Matthews, James; Bastatas, Lyndon

    2012-03-01

    There is a direct relation between the survival of a patient diagnosed with prostate or breast cancer and the metastatic potential of the patient's cancer. It is therefore extremely important to prognose metastatic potentials. In this study we investigated whether the behaviors of cancer cells responding to our state of the art nano-patterns differ by the metastatic potential of the cancer cells. We have used lowly (LNCaP) and highly (CL-1) metastatic human prostate cancer cells and lowly (MCF-7) and highly (MB231) metastatic breast cancer cells. A surface functionalization study was then performed first on uniform gold and glass surfaces, then on gold nano-patterned surfaces made by nano-sphere lithography using nano-spheres in diameter of 200nm to 800nm. The gold surfaces were functionalized with fibronectin (FN) and confirmed through XPS analysis. The CL-1, MCF-7, and MB231 cells show similar proliferation on all surfaces regardless of the presence of FN, whereas LNCaP show a clear preference for FN coated surfaces. The proliferation of the LNCaP was reduced when grown on finer nano-scaffolds, but the more aggressive CL-1, MB231, and MCF-7 cells show an abnormal proliferation regardless of pattern size. The difference in adhesion is intrinsic and was verified through dual fluorescent imaging. Clear co-localization of actin-vinculin were found on CL-1, MCF-7, and MB231. However LNCaP cells showed the co-localization only on the tips of the cells. These results provide vital clues to the bio-mechanical differences between the cancer cells with different metastatic potential.

  1. Characterization and Functional Analysis of the MAL and MPH Loci for Maltose Utilization in Some Ale and Lager Yeast Strains

    PubMed Central

    Vidgren, Virve; Ruohonen, Laura; Londesborough, John

    2005-01-01

    Maltose and maltotriose are the major sugars in brewer's wort. Brewer's yeasts contain multiple genes for maltose transporters. It is not known which of these express functional transporters. We correlated maltose transport kinetics with the genotypes of some ale and lager yeasts. Maltose transport by two ale strains was strongly inhibited by other α-glucosides, suggesting the use of broad substrate specificity transporters, such as Agt1p. Maltose transport by three lager strains was weakly inhibited by other α-glucosides, suggesting the use of narrow substrate specificity transporters. Hybridization studies showed that all five strains contained complete MAL1, MAL2, MAL3, and MAL4 loci, except for one ale strain, which lacked a MAL2 locus. All five strains also contained both AGT1 (coding a broad specificity α-glucoside transporter) and MAL11 alleles. MPH genes (maltose permease homologues) were present in the lager but not in the ale strains. During growth on maltose, the lager strains expressed AGT1 at low levels and MALx1 genes at high levels, whereas the ale strains expressed AGT1 at high levels and MALx1 genes at low levels. MPHx expression was negligible in all strains. The AGT1 sequences from the ale strains encoded full-length (616 amino acid) polypeptides, but those from both sequenced lager strains encoded truncated (394 amino acid) polypeptides that are unlikely to be functional transporters. Thus, despite the apparently similar genotypes of these ale and lager strains revealed by hybridization, maltose is predominantly carried by AGT1-encoded transporters in the ale strains and by MALx1-encoded transporters in the lager strains. PMID:16332759

  2. 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. PMID:22031555

  3. 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.

  4. 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

  5. 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). PMID:26766137

  6. 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

  7. 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. PMID:23555280

  8. Repetitive flash x-ray generator utilizing a simple diode with a new type of energy-selective function

    NASA Astrophysics Data System (ADS)

    Sato, E.; Kimura, S.; Kawasaki, S.; Isobe, H.; Takahashi, K.; Tamakawa, Y.; Yanagisawa, T.

    1990-09-01

    The construction and the fundamental studies of a repetitive flash x-ray generator having a simple diode with an energy-selective function are described. This generator consisted of the following components: a constant high-voltage power supply, a high-voltage pulser, a repetitive high-energy impulse switching system, a turbo molecular pump, and a flash x-ray tube. The circuit of this pulser employed a modified two-stage surge Marx generator with a capacity during main discharge of 425pF. The x-ray tube was of the demountable-diode type which was connected to the turbo molecular pump and consisted of the following major devices: a rod-shaped anode tip made of tungsten, a disk cathode made of graphite, an aluminum filter, and a tube body made of glass. Two condensers inside of the pulser were charged from 40 to 60 kV, and the output voltage was about 1.9 times the charging voltage. The peak tube voltage was primarily determined by the anode-cathode (A-C) space, and the peak tube current was less than 0.6 kA. The peak tube voltage slightly increased when the charging voltage was increased, but the amount of change rate was small. Thus, the maximum photon energy could be easily controlled by varying the A-C space. The pulse width ranged from 40 to 100 ns, and the x-ray intensity was less than 1.0 μC/kg at 0.3 m per pulse. The repetitive frequency was less than 50 Hz, and the effective focal spot size was determined by the diameter of the anode tip and ranged from 0.5 to 3.0 mm in diameter.

  9. Functional expression and characterization of five wax ester synthases in Saccharomyces cerevisiae and their utility for biodiesel production

    PubMed Central

    2012-01-01

    Background Wax ester synthases (WSs) can synthesize wax esters from alcohols and fatty acyl coenzyme A thioesters. The knowledge of the preferred substrates for each WS allows the use of yeast cells for the production of wax esters that are high-value materials and can be used in a variety of industrial applications. The products of WSs include fatty acid ethyl esters, which can be directly used as biodiesel. Results Here, heterologous WSs derived from five different organisms were successfully expressed and evaluated for their substrate preference in Saccharomyces cerevisiae. We investigated the potential of the different WSs for biodiesel (that is, fatty acid ethyl esters) production in S. cerevisiae. All investigated WSs, from Acinetobacter baylyi ADP1, Marinobacter hydrocarbonoclasticus DSM 8798, Rhodococcus opacus PD630, Mus musculus C57BL/6 and Psychrobacter arcticus 273-4, have different substrate specificities, but they can all lead to the formation of biodiesel. The best biodiesel producing strain was found to be the one expressing WS from M. hydrocarbonoclasticus DSM 8798 that resulted in a biodiesel titer of 6.3 mg/L. To further enhance biodiesel production, acetyl coenzyme A carboxylase was up-regulated, which resulted in a 30% increase in biodiesel production. Conclusions Five WSs from different species were functionally expressed and their substrate preference characterized in S. cerevisiae, thus constructing cell factories for the production of specific kinds of wax ester. WS from M. hydrocarbonoclasticus showed the highest preference for ethanol compared to the other WSs, and could permit the engineered S. cerevisiae to produce biodiesel. PMID:22364438

  10. Defining Electron Backscatter Diffraction Resolution

    SciTech Connect

    El-Dasher, B S; Rollett, A D

    2005-02-07

    }{sub center} value is used to describe the overall system resolution, as it effectively quantifies the deviation of all orientations in the scan relative to the diffraction pattern least affected by distortions. The second is {omega}{sub max}, the largest misorientation angle possible between any pair of points in the dataset, and describes the worst possible case. Fig. 1 shows the effects of scan size and captured pattern resolution (bin size) on both angular values, illustrating that smaller scan and bin sizes have the effect of increasing angular resolution. However, it can be observed that the benefits of utilizing smaller bin sizes (and consequently slower data collection) diminish with scan size. Fig. 2 shows the effect of the number of pixels used in the Hough transform (defined as the ratio of pixels used to maximum possible pixels) on the angular values. It can be seen that the best angular resolutions are achieved at a pixel ratio of 0.80, again illustrating that the use of higher resolutions is not always beneficial. As evidenced by the results, the use of {omega}{sub center} and {omega}{sub max} not only permits the characterization of the angular resolution of an EBSD system, but they allow for a more efficient utilization of the system by identifying appropriate settings depending on the desired angular resolution [6].

  11. 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.

  12. 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

  13. Will anticipated future climatic conditions affect belowground C utilization? - Insights into the role of microbial functional groups in a temperate heath/grassland.

    NASA Astrophysics Data System (ADS)

    Reinsch, Sabine; Michelsen, Anders; Sárossy, Zsuzsa; Egsgaard, Helge; Kappel Schmidt, Inger; Jakobsen, Iver; Ambus, Per

    2013-04-01

    The global terrestrial soil organic matter stock is the biggest terrestrial carbon pool (1500 Pg C) of which about 4 % is turned over annually. Thus, terrestrial ecosystems have the potential to accelerate or diminish atmospheric climate change effects via belowground carbon processes. We investigated the effect of elevated CO2 (510 ppm), prolonged spring/summer droughts and increased temperature (1 ˚C) on belowground carbon allocation and on the recovery of carbon by the soil microbial community. An in-situ 13C-carbon pulse-labeling experiment was carried out in a temperate heath/grassland (Denmark) in May 2011. Recently assimilated 13C-carbon was traced into roots, soil and microbial biomass 1, 2 and 8 days after pulse-labeling. The importance of the microbial community in C utilization was investigated using 13C enrichment patterns in microbial functional groups on the basis of phospholipid fatty acids (PLFAs) in roots. Gram-negative and gram-positive bacteria were distinguished from the decomposer groups of actinomycetes (belonging to the group of gram-positive bacteria) and saprophytic fungi. Mycorrhizal fungi specific PLFAs were not detected probably due to limited sample size in combination with restricted sensitivity of the used GC-c-IRMS setup. Climate treatments did not affect 13C allocation into roots, soil and microbial biomass carbon and also the total microbial biomass size stayed unchanged as frequently observed. However, climate treatments changed the composition of the microbial community: elevated CO2 significantly reduced the abundance of gram-negative bacteria (17:0cy) but did not affect the abundance of decomposers. Drought favored the bacterial community whereas increased temperatures showed reduced abundance of gram-negative bacteria (19:0cy) and changed the actinomycetes community (10Me16:0, 10Me18:0). However, not only the microbial community composition was affected by the applied climatic conditions, but also the activity of microbial

  14. Utilization of specific and non-specific peptide interactions with inorganic nanomaterials on the surface of bacteriophage M13: Methodologies towards phage supported bi-functional materials

    NASA Astrophysics Data System (ADS)

    Avery, Kendra Nicole

    Many types of organisms create a variety of nano and micro scale materials from precursors available in their surrounding environments by a process called biomineralization. As scientists begin to understand how these organisms utilize specific and non-specific interactions with a variety of biopolymers such as chitin, peptides, proteins and nucleic acids with these precursors to create inorganic/organic composite materials, they have begun to wonder about the synthesis of other types of non-biologically templated synthetic techniques that might be possible. Bioengineered organisms and biopolymers have begun to be used for these types of studies. A variety of selection techniques exist for discovering biopolymers with an affinity for a target material, however, one of the most notable is a technique called peptide phage display. This is a technique that utilizes a commercially available randomized peptide library attached at the tip of the filamentous bacteriophage M13. In this dissertation capabilities of bacteriophage M13 are explored in regard to the creation of bi-functional nano materials by exploiting both specific peptide interactions as well as non-specific peptide interactions on the surface of the organism. Chapter 2 focuses on utilizing the specific peptide interactions of the randomized library at pIII in order to discover peptides with high binding affinity for a variety of nanomaterials. Selection studies called biopanning are performed on a variety of nanomaterials such as CaMoO4, allotropes of Ni, Fe2O3 and Fe3O4, and Rh and Pt with the fcc type crystal structure. Similarities and differences between peptides discovered for these materials are discussed. Chapter 3 focuses on utilizing the non-specific peptide interactions on the long axis of M13 called pVIII. The pVIII region consists of 2700 copies of the same 50 amino acid protein which as a negatively charged domain which is exposed to solution. The pVIII region therefore provides the surface of

  15. The utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool and other bleeding questionnaires in assessing the bleeding phenotype in two platelet function defects.

    PubMed

    Kaur, Harmanpreet; Borhany, Munira; Azzam, Hanan; Costa-Lima, Carolina; Ozelo, Margareth; Othman, Maha

    2016-07-01

    The main objective of this study is to investigate the utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) in comparison with the condensed form of Molecular and Clinical Markers for the Diagnosis and Management of type 1 and WHO BATs, in assessing bleeding in two well known and clinically significant platelet function defects. Thirty-eight patients previously diagnosed with Glanzmann's thrombasthenia and 10 with Bernard-Soulier syndrome (BSS) were analyzed. Bleeding scores were significantly higher than that of controls using both electronic bleeding questionnaire (eBQ) and ISTH-BAT with no significant difference between both tools. ISTH-BAT had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 76.2%, 0.9 and 1. This was closely similar to eBQ. Both ISTH-BAT and eBQ are efficient in BSS and Glanzmann's thrombasthenia. However, given the ISTH recommendation, ISTH-BAT should be adopted. Larger study including other platelet defects will enhance its utility and support the integration of bleeding scores with standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders. PMID:27100304

  16. Functional Characterization of Sodium-dependent Multivitamin Transporter (SMVT) in MDCK-MDR1 cells and its Utilization as a Target for Drug Delivery

    PubMed Central

    Luo, Shuanghui; Kansara, Viral S.; Zhu, Xiaodong; Pal, Dhananjay; Mitra, Ashim. K.

    2008-01-01

    The objective of this research is to characterize a sodium-dependent multivitamin transporter (SMVT) in MDCK-MDR1 cells (Madin-Darby canine kidney cells transfected with the human MDR1 gene) and to investigate the feasibility of utilizing MDCK-MDR1 cell line as an in vitro model to study the permeability of biotin-conjugated prodrugs of anti-HIV protease inhibitors. Mechanism of [3H] biotin uptake and transport was delineated. Transepithelial permeability of the biotin conjugated prodrug i.e. biotin-saquinavir was also studied. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out to confirm the existence of SMVT in MDCK-MDR1 cells. Biotin uptake was Na+, pH, and temperature dependent, but energyindependent. Transepithelial transport studies of biotin-saquinavir in MDCK-MDR1, wild type MDCK, and Caco-2 cells revealed that permeability of biotin-saquinavir was similar in all three cell lines. A band of SMVT mRNA at 862 bp was identified by RT-PCR. A sodium-dependent multivitamin transporter, SMVT, responsible for biotin uptake and transport, was identified and functionally characterized in MDCK-MDR1 cells. Therefore, MDCK-MDR1 cell line may be utilized as an in vitro model to study the permeability of biotin conjugated prodrugs such as HIV protease inhibitors. PMID:16749865

  17. 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. PMID:24870365

  18. 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.

  19. 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

  20. Utility of sequenced genomes for microsatellite marker development in non-model organisms: a case study of functionally important genes in nine-spined sticklebacks (Pungitius pungitius)

    PubMed Central

    2010-01-01

    Background Identification of genes involved in adaptation and speciation by targeting specific genes of interest has become a plausible strategy also for non-model organisms. We investigated the potential utility of available sequenced fish genomes to develop microsatellite (cf. simple sequence repeat, SSR) markers for functionally important genes in nine-spined sticklebacks (Pungitius pungitius), as well as cross-species transferability of SSR primers from three-spined (Gasterosteus aculeatus) to nine-spined sticklebacks. In addition, we examined the patterns and degree of SSR conservation between these species using their aligned sequences. Results Cross-species amplification success was lower for SSR markers located in or around functionally important genes (27 out of 158) than for those randomly derived from genomic (35 out of 101) and cDNA (35 out of 87) libraries. Polymorphism was observed at a large proportion (65%) of the cross-amplified loci independently of SSR type. To develop SSR markers for functionally important genes in nine-spined sticklebacks, SSR locations were surveyed in or around 67 target genes based on the three-spined stickleback genome and these regions were sequenced with primers designed from conserved sequences in sequenced fish genomes. Out of the 81 SSRs identified in the sequenced regions (44,084 bp), 57 exhibited the same motifs at the same locations as in the three-spined stickleback. Di- and trinucleotide SSRs appeared to be highly conserved whereas mononucleotide SSRs were less so. Species-specific primers were designed to amplify 58 SSRs using the sequences of nine-spined sticklebacks. Conclusions Our results demonstrated that a large proportion of SSRs are conserved in the species that have diverged more than 10 million years ago. Therefore, the three-spined stickleback genome can be used to predict SSR locations in the nine-spined stickleback genome. While cross-species utility of SSR primers is limited due to low amplification

  1. wssa_utils: WSSA 12 micron dust map utilities

    NASA Astrophysics Data System (ADS)

    Meisner, Aaron M.; Finkbeiner, Douglas P.

    2014-02-01

    wssa_utils contains utilities for accessing the full-sky, high-resolution maps of the WSSA 12 micron data release. Implementations in both Python and IDL are included. The code allows users to sample values at (longitude, latitude) coordinates of interest with ease, transparently mapping coordinates to WSSA tiles and performing interpolation. The wssa_utils software also serves to define a unique WSSA 12 micron flux at every location on the sky.

  2. Endothelial progenitor cells: identity defined?

    PubMed Central

    Timmermans, Frank; Plum, Jean; Yöder, Mervin C; Ingram, David A; Vandekerckhove, Bart; Case, Jamie

    2009-01-01

    Abstract In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells. PMID:19067770

  3. 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…

  4. 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.

  5. 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

  6. 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.…

  7. Crack-Defined Electronic Nanogaps.

    PubMed

    Dubois, Valentin; Niklaus, Frank; Stemme, Göran

    2016-03-01

    Achieving near-atomic-scale electronic nanogaps in a reliable and scalable manner will facilitate fundamental advances in molecular detection, plasmonics, and nanoelectronics. Here, a method is shown for realizing crack-defined nanogaps separating TiN electrodes, allowing parallel and scalable fabrication of arrays of sub-10 nm electronic nanogaps featuring individually defined gap widths. PMID:26784270

  8. 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.

  9. 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.

  10. 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.

  11. Praxis conversion utilities

    SciTech Connect

    Duffy, J.M.; Greenwood, J.R.; Shapiro, R.

    1981-12-02

    The Praxis Conversion Utilities are a set of Praxis routines which convert data objects to/from Ascii strings. For instance, the AsciiInteger function converts an array of characters to an integer value. These routines are implemented as a consistent set of utilities with complete control over the various formatting options and fill characters. Most of the parameters for each routine are optional such that they are easy to invoke for standard cases, yet allowing the detailed control when necessary.

  12. 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)

  13. 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.

  14. 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

  15. BIOMASS UTILIZATION

    EPA Science Inventory

    The biomass utilization task consists of the evaluation of a biomass conversion technology including research and development initiatives. The project is expected to provide information on co-control of pollutants, as well as, to prove the feasibility of biomass conversion techn...

  16. 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…

  17. 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.

  18. SPAR data handling utilities

    NASA Technical Reports Server (NTRS)

    Giles, G. L.; Haftka, R. T.

    1978-01-01

    The SPAR computer software system is a collection of processors that perform particular steps in the finite-element structural analysis procedure. The data generated by each processor are stored on a data base complex residing on an auxiliary storage device, and these data are then used by subsequent processors. The SPAR data handling utilities use routines to transfer data between the processors and the data base complex. A detailed description of the data base complex organization is presented. A discussion of how these SPAR data handling utilities are used in an application program to perform desired user functions is given with the steps necessary to convert an existing program to a SPAR processor by incorporating these utilities. Finally, a sample SPAR processor is included to illustrate the use of the data handling utilities.

  19. 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),…

  20. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  1. 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.

  2. Young black women: defining health.

    PubMed

    Hargrove, H J; Keller, C

    1993-01-01

    The purpose of this study was to elicit a definition of health as described by young Black women and to characterize the factors related to their definitions of health. The research questions were: (a) How do young Black women define health and (b) what factors are related to their definition of health? Using interviews and open-ended questions, an exploratory descriptive design examined the factors which contribute to the definition of health. Twenty-two young Black women between the ages of 21 and 40 comprised the sample. A wide range of incomes, occupations, educational levels, marital status, and family sizes were represented. The informants defined health as comprising those characteristics, behaviors, and/or activities which include: (a) having or avoiding a disease, (b) the presence or absence of obesity, (c) experiencing and reducing stress, (d) good and bad health habits, (e) eating good and bad foods, and (f) engaging (or not) in exercise. PMID:8106873

  3. Defining and managing sustainable yield.

    PubMed

    Maimone, Mark

    2004-01-01

    Ground water resource management programs are paying increasing attention to the integration of ground water and surface water in the planning process. Many plans, however, show a sophistication in approach and presentation that masks a fundamental weakness in the overall analysis. The plans usually discuss issues of demand and yield, yet never directly address a fundamental issue behind the plan--how to define sustainable yield of an aquifer system. This paper points out a number of considerations that must be addressed in defining sustainable yield in order to make the definition more useful in practical water resource planning studies. These include consideration for the spatial and temporal aspects of the problem, the development of a conceptual water balance, the influence of boundaries and changes in technology on the definition, the need to examine water demand as well as available supply, the need for stakeholder involvement, and the issue of uncertainty in our understanding of the components of the hydrologic system. PMID:15584295

  4. Defined DNA/nanoparticle conjugates.

    PubMed

    Ackerson, Christopher J; Sykes, Michael T; Kornberg, Roger D

    2005-09-20

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. PMID:16155122

  5. 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

  6. Identification of a functional 2-keto-myo-inositol dehydratase gene of Sinorhizobium fredii USDA191 required for myo-inositol utilization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sinorhizobium fredii USDA191 is a Gram-negative bacterium capable of forming nitrogen-fixing nodules on soybean roots. The USDA191 idhA gene encoding myo-inositol dehydrogenase, an enzyme necessary for myo-inositol utilization, is known to be involved in competitive nodulation and nitrogen fixation....

  7. Federal Funding for Education Knowledge Production and Utilization: KPU Function, by Agency. R&D Systems Studies. Technical Report No. 2.

    ERIC Educational Resources Information Center

    Mason, Ward S.; And Others

    This report examines support for education Knowledge Production and Utilization (KPU) using data provided by the National Academy of Sciences (NAS) Study Project on Social Research and Development. The scope of education KPU is discussed in terms of social policy areas relevant to education and activities relevant to KPU. The conceptual framework…

  8. Observer models for statistically-defined backgrounds

    NASA Astrophysics Data System (ADS)

    Burgess, Arthur E.

    1994-04-01

    Investigation of human signal-detection performance for noise- limited tasks with statistically defined signal or image parameters represents a step towards clinical realism. However, the ideal observer procedure is then usually nonlinear, and analysis becomes mathematically intractable. Two linear but suboptimal observer models, the Hotelling observer and the non- prewhitening (NPW) matched filter, have been proposed for mathematical convenience. Experiments by Rolland and Barrett involving detection of signals in white noise superimposed on statistically defined backgrounds showed that the Hotelling model gave a good fit while the simple NPW matched filter gave a poor fit. It will be shown that the NPW model can be modified to fit their data by adding a spatial frequency filter of shape similar to the human contrast sensitivity function. The best fit is obtained using an eye filter model, E(f) equals f1.3 exp(-cf2) with c selected to give a peak at 4 cycles per degree.

  9. 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.

  10. 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

  11. 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

  12. Presence or absence of a known DKA precipitant defines distinct syndromes of “A-β+” Ketosis-Prone Diabetes (KPD) based on long-term beta cell function, HLA class II alleles, and gender predilection

    PubMed Central

    Nalini, Ramaswami; Ozer, Kerem; Maldonado, Mario; Patel, Sanjeet G.; Hampe, Christiane S.; Guthikonda, Anu; Villanueva, Jesus; Smith, E. O'Brian; Gaur, Lakshmi K.; Balasubramanyam, Ashok

    2010-01-01

    Objective Ketosis prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with “A-β+” KPD (absent autoantibodies and preserved beta cell function) segregated into two subgroups with distinct evolution of beta 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 DKA. Hence we performed a comprehensive analysis of A-β+ KPD patients presenting with “provoked” compared to “unprovoked” DKA. Methods Clinical, biochemical and beta cell functional characteristics were compared between provoked and unprovoked A-β+ KPD patients followed prospectively for 1-8 years. HLA class II allele frequencies were compared between these two groups and population controls. Results Unprovoked A-β+ KPD patients (n=83) had greater BMI, 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 HLA class II type 1 diabetes susceptibility alleles DQB1*0302 (than the unprovoked group or population controls), and DRB1*04 (than the unprovoked group), while the unprovoked group had a higher frequency of the protective allele DQB1*0602. Beta 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. Conclusions “Unprovoked” A-β+ KPD is a distinct syndrome characterized by reversible beta cell dysfunction with male predominance and increased frequency of DQB1*0602, while “provoked” A-β+ KPD is characterized by progressive loss of beta cell reserve and increased frequency of DQB1*0302 and DRB1*04. Unprovoked DKA predicts long-term beta cell functional

  13. Defined DNA/nanoparticle conjugates

    NASA Astrophysics Data System (ADS)

    Ackerson, Christopher J.; Sykes, Michael T.; Kornberg, Roger D.

    2005-09-01

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. Freely available online through the PNAS open access option.

  14. 16 CFR 238.0 - Bait advertising defined. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring but insincere offer to sell a product or service which the advertiser in truth does not intend or want to sell... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Bait advertising defined. 1 238.0......

  15. Nonviable mutants of simian virus 40 with deletions near the 3' end of gene A define a function for large T antigen required after onset of viral DNA replication.

    PubMed Central

    Tornow, J; Cole, C N

    1983-01-01

    Deletion mutants of simian virus 40 (SV40) with lesions at the three DdeI sites near the 3' end of the early region were constructed. Mutants with deletions at 0.203 and 0.219 map units (mu) which did not change the large T antigen reading frame were viable. This extends slightly the upstream boundary for the location of viable mutants with deletions in the 3' end of the A gene. Mutants with frameshift deletions at 0.193 and 0.219 mu were nonviable. These are the first nonviable mutants with deletions in this portion of the A gene. None of the three nonviable mutants with deletions at 0.219 mu produced progeny viral DNA. These three mutants all used the alternate reading frame located in this portion of the SV40 early region. The mutant with a deletion at 0.193 mu, dlA2459, was positive for viral DNA replication and was defective for adenovirus helper function. All of these mutations were located in the portion of the SV40 large T antigen which has no homology to the polyoma T antigens. These results indicate that this portion of large T antigen is required for some late step in the viral growth cycle and suggest that adenovirus helper function is required for productive infection by SV40. Images PMID:6312080

  16. 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. PMID:26072824

  17. 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…

  18. 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.

  19. 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

  20. 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

    NASA Astrophysics Data System (ADS)

    Maranzana, Andrea; Giordana, Anna; Indarto, Antonius; Tonachini, Glauco; Barone, Vincenzo; Causà, Mauro; Pavone, Michele

    2013-12-01

    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

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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 Central

    Piasta, Kene N.; Ulliman, Caleb J.; Slivka, Peter F.; Crane, Brian R.; Falke, Joseph J.

    2013-01-01

    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 (P5) 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 TAM-IDS (Tryptophan and Alanine Mutation to Identify Docking Sites) 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

  6. Molecular characterization of the S-layer gene, sbpA, of Bacillus sphaericus CCM 2177 and production of a functional S-layer fusion protein with the ability to recrystallize in a defined orientation while presenting the fused allergen.

    PubMed

    Ilk, Nicola; Völlenkle, Christine; Egelseer, Eva M; Breitwieser, Andreas; Sleytr, Uwe B; Sára, Margit

    2002-07-01

    The nucleotide sequence encoding the crystalline bacterial cell surface (S-layer) protein SbpA of Bacillus sphaericus CCM 2177 was determined by a PCR-based technique using four overlapping fragments. The entire sbpA sequence indicated one open reading frame of 3,804 bp encoding a protein of 1,268 amino acids with a theoretical molecular mass of 132,062 Da and a calculated isoelectric point of 4.69. The N-terminal part of SbpA, which is involved in anchoring the S-layer subunits via a distinct type of secondary cell wall polymer to the rigid cell wall layer, comprises three S-layer-homologous motifs. For screening of amino acid positions located on the outer surface of the square S-layer lattice, the sequence encoding Strep-tag I, showing affinity to streptavidin, was linked to the 5' end of the sequence encoding the recombinant S-layer protein (rSbpA) or a C-terminally truncated form (rSbpA(31-1068)). The deletion of 200 C-terminal amino acids did not interfere with the self-assembly properties of the S-layer protein but significantly increased the accessibility of Strep-tag I. Thus, the sequence encoding the major birch pollen allergen (Bet v1) was fused via a short linker to the sequence encoding the C-terminally truncated form rSpbA(31-1068). Labeling of the square S-layer lattice formed by recrystallization of rSbpA(31-1068)/Bet v1 on peptidoglycan-containing sacculi with a Bet v1-specific monoclonal mouse antibody demonstrated the functionality of the fused protein sequence and its location on the outer surface of the S-layer lattice. The specific interactions between the N-terminal part of SbpA and the secondary cell wall polymer will be exploited for an oriented binding of the S-layer fusion protein on solid supports to generate regularly structured functional protein lattices. PMID:12089001

  7. 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

  8. 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. PMID:25622889

  9. 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

  10. 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.

  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. 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.

  13. Development and evaluation of a distribution automation system for an Indian utility

    SciTech Connect

    Rao, M.V.K.; Pandurangam, J.V.; Peri, R.; Clinard, K.N.; Krishna, C.R.

    1994-12-31

    This paper describes a study conducted by the Andhra Pradesh State Electricity Board (APSEB), India, and ECC, Inc., USA for the design of a distribution automation system (DAS). Distribution automation functions applicable to an Indian utility were identified. Communications technologies that are capable of meeting DAS requirements were evaluated, and a communications systems suitable for India was defined. A benefit/cost analysis was performed; first for a basic DAS and then for additional distribution automation functions.

  14. 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

  15. 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

  16. The spatiotemporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.

    PubMed

    Vastagh, Csaba; Schwirtlich, Marija; Kwakowsky, Andrea; Erdélyi, Ferenc; Margolis, Frank L; Yanagawa, Yuchio; Katarova, Zoya; Szabó, Gábor

    2015-03-01

    Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. PMID:25125027

  17. 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...

  18. Isobaric-Isothermal Molecular Dynamics Utilizing Density Functional Theory: An Assessment of the Structure and Density of Water at Near-Ambient Conditions

    SciTech Connect

    Schmidt, J; VandeVondele, J; Kuo, I W; Sebastiani, D; Siepmann, J I; Hutter, J; Mundy, C J

    2009-03-06

    We present herein a comprehensive density functional theory study toward assessing the accuracy of two popular gradient-corrected exchange correlation functionals on the structure and density of liquid water at near ambient conditions in the isobaric-isothermal ensemble. Our results indicate that both PBE and BLYP functionals under predict the density and over structure the liquid. Adding the dispersion correction due to Grimme(1, 2) improves the predicted densities for both BLYP and PBE in a significant manner. Moreover, the addition of the dispersion correction for BLYP yields an oxygen-oxygen radial distribution function in excellent agreement with experiment. Thus, we conclude that one can obtain a very satisfactory model for water using BLYP and a correction for dispersion.

  19. 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.

  20. Greater Utilization of Neural-Circuits Related to Executive Functions is Associated with Better Reading: A Longitudinal fMRI Study Using the Verb Generation Task

    PubMed Central

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J.; Gozdas, Elveda; Holland, Scott K.

    2014-01-01

    Introduction: Reading is an acquired-developmental ability that relies on intact language and executive function skills. Verbal fluency tasks (such as verb generation) also engage language and executive function skills. Performance of such tasks matures with normal language development, and is independent of reading proficiency. In this longitudinal fMRI study, we aim to examine the association between maturation of neural-circuits supporting both executive functions and language (assessed using verb generation) with reading proficiency achieved in adolescence with a focus on left-lateralization typical for language proficiency. Methods: Normalized fMRI data from the verb generation task was collected from 16 healthy children at ages 7, 11, and 17 years and was correlated with reading scores at 17 years of age. Lateralization indices were calculated in key language, reading, and executive function-related regions in all age groups. Results: Typical development was associated with (i) increasingly left-lateralized patterns in language regions (ii) more profound left-lateralized activation for reading and executive function-related regions when correlating with reading scores, (iii) greater involvement of frontal and parietal regions (in older children), and of the anterior frontal cortex (in younger children). Conclusion: We suggest that reading and verb generation share mutual neural-circuits during development with major reliance on regions related to executive functions and reading. The results are discussed in the context of the dual-networks architecture model. PMID:24999322

  1. 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.

  2. 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

  3. Sputter-induced cross-contamination in analytical AES and XPS instrumentation: utilization of the effect for the in situ deposition of ultrathin functional layers.

    PubMed

    Scheithauer, Uwe

    2013-09-01

    Cross-contamination is observed on sample surfaces by Auger electron spectroscopy and X-ray photoelectron spectroscopy if multiple samples are mounted on one sample holder and a neighbouring sample was sputter depth profiling. During sputter depth profiling, sputtered material is deposited on inner surfaces of the instrument. In a secondary sputter process, which is due to species leaving the primary sputter target with higher kinetic energy, the previously deposited material is transported from the inner surfaces to the other samples mounted on the sample holder. This reflective sputtering is utilized to deposit ultrathin layers on sample surfaces for X-ray photoelectron spectroscopy binding energy referencing purposes and to build up ultrathin conductive layers to make possible Auger electron spectroscopy measurements on insulating samples. PMID:23462980

  4. Functional characterization of VC1929 of Vibrio cholerae El Tor: role in mannose-sensitive haemagglutination, virulence and utilization of sialic acid.

    PubMed

    Sharma, Sandeep K; Moe, The Su; Srivastava, Ranjana; Chandra, Deepak; Srivastava, Brahm S

    2011-11-01

    The nonadhesive mutant CD11 of Vibrio cholerae El Tor, defective in expression of mannose-sensitive haemagglutinin, lacks a protein when compared with its parent strain. Determination of the amino acid sequence revealed the identity of the protein as the product of VC1929, which is annotated to encode a protein, DctP, involved in the transport of C₄-dicarboxylates. We cloned the dctP gene in pUC19 vector and expressed it in mutant CD11. Expression of DctP in the resulting complemented strain restored virulence, adhesive and colonizing capabilities, mannose-sensitive haemagglutination (MSHA) and ability to grow in medium containing sialic acid as a sole carbon source. The mutation in CD11 was caused by insertion of an adenine nucleotide in the reading frame of dctP. Recombinant purified DctP protein showed MSHA of human red blood cells, and protected rabbits against infection by V. cholerae. The protein was localized in membrane and cell wall fractions. The mutant, recombinant CD11 expressing DctP and parent strains were grown in M9 minimal medium in the presence of various carbohydrates (glucose, malate, fumarate, succinate or N-acetylneuraminic acid). The mutant was unable to grow in minimal medium containing N-acetylneuraminic acid (sialic acid) as the sole carbon source whereas the recombinant and parent strains utilized all the sugars tested. It is concluded that DctP is a mannose-sensitive haemagglutinin and a virulence factor and is involved in the utilization of sialic acid. PMID:21873407

  5. 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…

  6. 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…

  7. 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

  8. 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…

  9. 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.

  10. Defining a Standard Metric for Electricity Savings

    NASA Astrophysics Data System (ADS)

    Koomey, Jonathan; Akbari, Hashem; Blumstein, Carl; Brown, Marilyn; Brown, Richard; Budnitz, Robert; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H.; Fisk, William J.; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, José; 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; McAuliffe, Pat; 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.; Socolow, Robert H.; Sweeney, James L.; Verdict, Malcolm; von Meier, Alexandra; Vorsatz, Diana; Wang, Devra; Weinberg, Carl; Wilk, Richard; Wilson, John; Woodward, Jane; Worrell, Ernst

    2011-11-01

    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 that 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 like billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this article 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-megawatt existing coal plant operating at a 70% capacity factor with 7% T&D losses. Displacing such a plant for one year would save 3 billion kWh/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.

  11. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    DOE PAGESBeta

    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 workingmore » 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.« less

  12. 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 7-methoxy-4-(trifluoromethyl)coumarin (7-MFC). CYP2B35 had no dealkylation activity with 7-MFC or 7-EFC. Furthermore, the new CYP2B-4-CPI-bound structures were used as templates for docking the 7-substituted coumarin derivatives, which revealed orientations consistent with the functional studies. In addition, the observation of multiple -Cl and -NH-π interactions of 4-CPI with the aromatic side chains in the CYP2B35 and CYP2B37 structures provides insight into the influence of such functional groups on CYP2B ligand binding affinity and specificity. To conclude, structural, computational, and functional analysis revealed striking differences between the active sites of CYP2B35 and CYP2B37 that will aid in the elucidation of new structure-activity relationships. PMID:26826176

  13. 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.

  14. Assessing change in cognitive function in dementia: the relative utilities of the Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Cognitive Drug Research system.

    PubMed

    Wesnes, Keith A

    2008-01-01

    This paper considers the suitability of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) as the gold standard in registration trials of treatments for Alzheimer's disease. Working groups have recommended replacing the ADAS-cog if suitable automated alternatives can be found. This paper makes the case for the Cognitive Drug Research (CDR) computerised cognitive assessment system, as an example of a suitable instrument to replace the ADAS-cog. The CDR system has been widely used in dementia work for 20 years and shows good correlations to the ADAS-cog, while additionally assessing the domains of attention, working memory, information processing and retrieval speed of information held in memory. The utility of the system in evaluating and differentiating the major dementias will be described, as well as its ability to track deterioration over time. Its validation as a core measure of cognitive dysfunction in the dementias will be described, as will work showing that various CDR measures relate closely to activities of daily living. The sensitivity of the CDR system to anticholinesterases will be described in Alzheimer's disease, dementia with Lewy bodies and Parkinson's dementia. Finally, the CDR system has a large normative database which allows treatment effects in dementia to be put into an unambiguous clinical perspective. PMID:18322407

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Twist1 activity thresholds define multiple functions in limb development

    PubMed Central

    Krawchuk, Dayana; Weiner, Shoshana J.; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    Summary The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in the anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity. PMID:20732316

  20. Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Grasso, Catherine S.; Tang, Yujie; Truffaux, Nathalene; Berlow, Noah E.; Liu, Lining; Debily, Marie-Anne; Quist, Michael J.; Davis, Lara E.; Huang, Elaine C.; Woo, Pamelyn J; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Sun, Wenchao; Kogiso, Mari; Du, Yuchen; Lin, Qi; Huang, Yulun; Hütt-Cabezas, Marianne; Warren, Katherine E.; Dret, Ludivine Le; Meltzer, Paul S.; Mao, Hua; Quezado, Martha; van Vuurden, Dannis G.; Abraham, Jinu; Fouladi, Maryam; Svalina, Matthew N.; Wang, Nicholas; Hawkins, Cynthia; Nazarian, Javad; Alonso, Marta M.; Raabe, Eric; Hulleman, Esther; Spellman, Paul T.; Li, Xiao-Nan; Keller, Charles; Pal, Ranadip; Grill, Jacques; Monje, Michelle

    2015-01-01

    Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated efficacy in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat with histone demethylase inhibitor GSKJ4 revealed synergy. Together, these data suggest a promising therapeutic strategy for DIPG. PMID:25939062

  1. Functional validation of cadherin as a receptor of Bt toxin Cry1Ac in Helicoverpa armigera utilizing the CRISPR/Cas9 system.

    PubMed

    Wang, Jing; Zhang, Haonan; Wang, Huidong; Zhao, Shan; Zuo, Yayun; Yang, Yihua; Wu, Yidong

    2016-09-01

    Cadherins have been identified as receptors of Bacillus thuringiensis (Bt) Cry1A toxins in several lepidopteran insects including the cotton bollworm, Helicoverpa armigera. Disruption of the cadherin gene HaCad has been genetically linked to resistance to Bt toxin Cry1Ac in H. armigera. By using the CRISPR/Cas9 genome editing system (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9), HaCad from the Cry1Ac-susceptible SCD strain of H. armigera was successfully knocked out. A single positive CRISPR event with a frame shift deletion of 4 nucleotides was identified and made homozygous to create a knockout line named SCD-Cad. Western blotting confirmed that HaCad was no longer expressed in the SCD-Cad line while an intact HaCad of 210 kDa was present in the parental SCD strain. Insecticide bioassays were used to show that SCD-Cad exhibited 549-fold resistance to Cry1Ac compared with SCD, but no significant change in susceptibility to Cry2Ab. Our results not only provide strong reverse genetics evidence for HaCad as a functional receptor of Cry1Ac, but also demonstrate that the CRISPR/Cas9 technique can act as a powerful and efficient genome editing tool to study gene function in a global agricultural pest, H. armigera. PMID:27343383

  2. Sociometabolic transitions defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Fischer-Kowalski, Prof; Krausmann, Prof; Pallua, Mag

    2014-05-01

    We search for a valid and quantifiable description of how and when humans acquire the ability to dominate major features of the Earth system. While common approaches (such as Kaplan et al. 2011 for example) seek to quantify the human impact upon the carbon cycle by identifying the area of land cleared by humans, we choose a more comprehensive path. Our point of departure is different human modes of subsistence, and we base our analysis on their social metabolism, in particular their energy metabolism. As a starting point, we use Ehrlich's classical IPAT formula, and give it a specific interpretation: human impact on Earth equals population size times affluence (interpreted as energy available per person) times technology - for each mode of subsistence. The overall impact (or rather human pressure) then equals the composite sum of these. We qualitatively describe the functional characteristics of hunter gatherers, agrarian and industrial modes of subsistence such as population dynamics, energy regime and the technologies by which they interact with their environment. In a 'toy' model, we translate these considerations into global numbers for the past millennia: we estimate the respective population sizes and affluence (energy), and finally also technology concerning its impact on the carbon cycle. Along this path, there are a number of findings: that it is reasonably possible to cross-check the size of pre-industrial agrarian populations from the size of urban populations; that it was in the last centuries BC that the size of agrarian populations exceeded those of hunter gatherers; that there seems to be a loglinear function of increasing average energetic metabolic rate from human basic metabolism across hunter gatherers and the agrarian mode to the industrial regime; and that from AD 1500 onwards, there is a very close relation between the urban population and fossil fuel use. We see a major historical dividing line around AD 1500: up to then, human population

  3. Utilizing the integrated difference of two survival functions to quantify the treatment contrast for designing, monitoring and analyzing a comparative clinical study

    PubMed Central

    Zhao, Lihui; Tian, Lu; Uno, Hajime; Solomon, Scott D.; Pfeffer, Marc A.; Schindler, Jerald S.; Wei, L. J.

    2013-01-01

    Background Consider a comparative, randomized clinical study with a specific event time as the primary endpoint. In the presence of censoring, standard methods of summarizing the treatment difference are based on Kaplan-Meier curves, the logrank test and the point and interval estimates via Cox’s procedure. Moreover, for designing and monitoring the study, one usually utilizes an event-driven scheme to determine the sample sizes and interim analysis time points. Purpose When the proportional hazards assumption is violated, the logrank test may not have sufficient power to detect the difference between two event time distributions. The resulting hazard ratio estimate is difficult, if not impossible, to interpret as a treatment contrast. When the event rates are low, the corresponding interval estimate for the “hazard ratio” can be quite large due to the fact that the interval length depends on the observed numbers of events. This may indicate that there is not enough information for making inferences about the treatment comparison even when there is no difference between two groups. This situation is quite common for a post marketing safety study. We need an alternative way to quantify the group difference. Methods Instead of quantifying the treatment group difference using the hazard ratio, we consider an easily interpretable and model-free parameter, the integrated survival rate difference over a pre-specified time interval, as an alternative. We present the inference procedures for such a treatment contrast. This approach is purely nonparametric and does not need any model assumption such as the proportional hazards. Moreover, when we deal with equivalence or non-inferiority studies and the event rates are low, our procedure would provide more information about the treatment difference. We used a cardiovascular trial data set to illustrate our approach. Results The results using the integrated event rate differences have a heuristic interpretation for the

  4. Classical subjective expected utility

    PubMed Central

    Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

    2013-01-01

    We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty. PMID:23559375

  5. Coming utility squeeze play

    SciTech Connect

    Stoiaken, L.N.

    1988-02-01

    Like a sleeping giant, utilities are waking up and preparing to participate in the increasingly competitive power production industry. Some are establishing subsidiaries to participate in join venture deals with independents. Others are competing by offering lucrative discount or deferral rates to important industrial and commercial customers considering cogeneration. And now, a third approach is beginning to shape up- the disaggregation of generation assets into a separate generation company, or genco. This article briefly discusses these three and also devotes brief sections to functional segmentation and The regulatory arena.

  6. Classical subjective expected utility.

    PubMed

    Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

    2013-04-23

    We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty. PMID:23559375

  7. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging: A potential utility for the evaluation of regional liver function impairment following transcatheter arterial chemoembolization

    PubMed Central

    XIAO, YU-DONG; PAUDEL, RAMCHANDRA; LIU, HUAN; ZHANG, BIN; MA, CONG; ZHOU, SHUN-KE

    2015-01-01

    The present study aimed to evaluate regional liver function impairment following transcatheter arterial chemoembolization (TACE), assessed by magnetic resonance imaging (MRI) enhanced by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). Additionally, this study evaluated the associations between signal intensity and various clinical factors. A prospective study was conducted between March 2012 and May 2013 with a total of 35 patients. Gd-EOB-DTPA-enhanced MRI was performed 3–5 days after TACE therapy. The signal to noise ratio (SNR) was subsequently calculated for healthy liver tissue regions and peritumoral regions, prior to and 20 min after Gd-EOB-DTPA administration. The correlation between clinical factors and relative SNR was assessed using Pearson’s correlation coefficient or Spearman’s rank correlation coefficient. Prior to Gd-EOB-DTPA administration, the SNR values showed no significant difference (t=1.341, P=0.191) in healthy liver tissue regions (50.53±15.99; range, 11.25–83.46) compared with peritumoral regions (49.81±15.85; range, 12.34–81.53). On measuring at 20 min following Gd-EOB-DTPA administration, the SNR in healthy liver tissue regions (82.55±33.33; range, 31.45–153.02) was significantly higher (t=3.732, P<0.001) compared with that in peritumoral regions (75.77±27.41; range, 31.42–144.49). The relative SNR in peritumoral regions correlated only with the quantity of iodized oil used during TACE therapy (r=0.528, P=0.003); the age, gender, diameter and blood supply of the tumor, or Child-Pugh class of the patient did not correlate with relative SNR. Gd-EOB-DTPA-enhanced MRI may be an effective way to evaluate regional liver function impairment following TACE therapy. PMID:25663880

  8. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  9. Defining microbiota for developing new probiotics

    PubMed Central

    Collado, Maria Carmen; Bäuerl, Christine; Pérez-Martínez, Gaspar

    2012-01-01

    The human body harbors complex communities of microbes that play a prominent role in human health. Detailed characterization of the microbiota in the target population forms the basis of probiotic use. Probiotics are defined as live bacterial preparations with clinically documented health effects in humans, and independent of their genus and species, probiotic strains are unique and their beneficial properties on human health have to be assessed in a case-by-case manner. Understanding the mechanisms by which probiotics influence microbiota would facilitate the use of probiotics for both dietary management and reduction in risk of specific diseases. The development of high throughput sequencing methods has allowed metagenomic approaches to study the human microbiome. These efforts are starting to generate an inventory of bacterial taxons and functional features bound to particular health or disease status that allow inferring aspects of the microbiome's function. In the future, this information will allow the rational design of dietary interventions aimed to improve consumer's health via modulation of the microbiota. PMID:23990820

  10. Defining muscle elastance as a parameter.

    PubMed

    Palladino, Joseph L; Noordergraaf, Abraham

    2007-01-01

    Functional descriptions of striated muscle are often based on the measured variables force and initial velocity of shortening, embodied as Hill's contractile element. The fundamental difficulty of describing the mechanical properties of muscle with a force-velocity relation that is set a priori, and the practical problem of the act of measurement changing muscle's force-velocity relation or elastance curve, are described. As an alternative, a new model of muscle contraction is presented, which characterizes muscle's contractile state with parameters, rather than variables. Muscle is treated as a force generator that is time, length, and velocity dependent. Muscle dynamics develop from a single equation based on the formation and relaxation of crossbridge bonds. This analytical function permits the calculation of muscle elastance via E(m)=[abstract: see text]. This new muscle model is defined independently from load properties, and muscle elastance is dynamic and reflects changing numbers of crossbridge bonds. This parameter is more representative of the mechanical properties of muscle than are variables such as muscle force and shortening velocity. PMID:18003207

  11. Genetic variation in feed consumption, growth, nutrient utilization efficiency and mitochondrial function within a farmed population of channel catfish (Ictalurus punctatus).

    PubMed

    Eya, Jonathan C; Ashame, Martha F; Pomeroy, Charles F; Manning, Bruce B; Peterson, Brian C

    2012-10-01

    We evaluated the effects of diets (32/4 or 36/6 percent protein/fat) and six channel catfish families for growth performance characteristics. Two families with fast- (C) and slow- (D) growth rate and with low and high feed efficiency (FE) were selected for analyses of mitochondrial complex enzymatic activities (I, II, III, and IV) and gene expression (ND1, CYTB, COX1, COX2, ATP6) levels in liver, muscle, and intestine. There were significant differences in growth rate and nutrient retention among the families. Mitochondrial enzymatic complex activities (I-V) in the tissues were all lower in family C. Four of the five genes were down-regulated in the liver and up-regulated in the muscle for the fast growing family C. There were significant differences between diets for some mitochondrial respiratory chain enzyme activities and gene expression levels. Significant diet×family interactions were observed for some enzyme activities and gene expression levels. Changes in mitochondrial respiratory chain enzyme activities and gene expression levels provide insight into the cellular mechanisms of fish with differences in growth rate and feed efficiency. Results also suggest that genotype×diet interactions should be accounted for when considering strategies for using mitochondrial function as a criteria in channel catfish selection programs for improved growth performance characteristics. PMID:22691874

  12. Some personal and historical notes on the utility of "deep-etch" electron microscopy for making cell structure/function correlations.

    PubMed

    Heuser, John E

    2014-11-01

    This brief essay talks up the advantages of metal replicas for electron microscopy and explains why they are still the best way to image frozen cells in the electron microscope. Then it explains our approach to freezing, namely the Van Harreveld trick of "slamming" living cells onto a supercold block of metal sprayed with liquid helium at -269ºC, and further talks up this slamming over the alternative of high-pressure freezing, which is much trickier but enjoys greater favor at the moment. This leads me to bemoan the fact that there are not more young investigators today who want to get their hands on electron microscopes and use our approach to get the most "true to life" views of cells out of them with a minimum of hassle. Finally, it ends with a few perspectives on my own career and concludes that, personally, I'm permanently stuck with the view of the "founding fathers" that cell ultrastructure will ultimately display and explain all of cell function, or as Palade said in his Nobel lecture,electron micrographs are "irresistible and half transparent … their meaning buried under only a few years of work," and "reasonable working hypotheses are already suggested by the ultrastructural organization itself." PMID:25360049

  13. Some personal and historical notes on the utility of “deep-etch” electron microscopy for making cell structure/function correlations

    PubMed Central

    Heuser, John E.

    2014-01-01

    This brief essay talks up the advantages of metal replicas for electron microscopy and explains why they are still the best way to image frozen cells in the electron microscope. Then it explains our approach to freezing, namely the Van Harreveld trick of “slamming” living cells onto a supercold block of metal sprayed with liquid helium at −269ºC, and further talks up this slamming over the alternative of high-pressure freezing, which is much trickier but enjoys greater favor at the moment. This leads me to bemoan the fact that there are not more young investigators today who want to get their hands on electron microscopes and use our approach to get the most “true to life” views of cells out of them with a minimum of hassle. Finally, it ends with a few perspectives on my own career and concludes that, personally, I'm permanently stuck with the view of the “founding fathers” that cell ultrastructure will ultimately display and explain all of cell function, or as Palade said in his Nobel lecture,electron micrographs are “irresistible and half transparent … their meaning buried under only a few years of work,” and “reasonable working hypotheses are already suggested by the ultrastructural organization itself.” PMID:25360049

  14. Defining human mesenchymal stem cell efficacy in vivo.

    PubMed

    Bonfield, Tracey L; Nolan Koloze, Mary T; Lennon, Donald P; Caplan, Arnold I

    2010-01-01

    Allogeneic human mesenchymal stem cells (hMSCs) can suppress graft versus host disease (GvHD) and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma. PMID:20974000

  15. Beware of Publicity! Perceived Distress of Negative Cyber Incidents and Implications for Defining Cyberbullying

    ERIC Educational Resources Information Center

    Pieschl, Stephanie; Kuhlmann, Christina; Porsch, Torsten

    2015-01-01

    Cyberbullying is usually defined by utilizing offline criteria for bullying ("repetition," "power imbalance," "intent to harm"). However, this ignores the potential relevance of cyber-specific factors ("publicity," "medium," "type" [i.e., denigration]). We compared six factors, each with…

  16. Defining moments in leadership character development.

    PubMed

    Bleich, Michael R

    2015-06-01

    Critical moments in life define one's character and clarify true values. Reflective leadership is espoused as an important practice for transformational leaders. Professional development educators can help surface and explore defining moments, strengthen leadership behavior with defining moments as a catalyst for change, and create safe spaces for leaders to expand their leadership capacity. PMID:26057159

  17. Defined contribution: a part of our future.

    PubMed Central

    Baugh, Reginald F.

    2003-01-01

    Rising employer health care costs and consumer backlash against managed care are trends fostering the development of defined contribution plans. Defined contribution plans limit employer responsibility to a fixed financial contribution rather than a benefit program and dramatically increase consumer responsibility for health care decision making. Possible outcomes of widespread adoption of defined contribution plans are presented. PMID:12934869

  18. 7 CFR 29.9201 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.9201 Section 29.9201 Agriculture... Tobacco Produced and Marketed in a Quota Area Definitions § 29.9201 Terms defined. As used in this subpart... hereinafter defined shall have the indicated meanings so assigned....

  19. 7 CFR 1206.200 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1206.200 Section 1206.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION Rules and Regulations § 1206.200 Terms defined. Unless otherwise defined in this subpart,...

  20. 7 CFR 1210.500 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1210.500 Section 1210.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Rules and Regulations Definitions § 1210.500 Terms defined. Unless otherwise defined in...

  1. 7 CFR 29.12 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.12 Section 29.12 Agriculture... INSPECTION Regulations Definitions § 29.12 Terms defined. As used in this subpart and in all instructions, forms, and documents in connection therewith, the words and phrases hereinafter defined shall have...

  2. 16 CFR 502.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 502.2 Section 502.2... FAIR PACKAGING AND LABELING ACT Definitions § 502.2 Terms defined. As used in this part, unless the... those terms are defined under part 500 of this chapter. (b) The term packager and labeler means...

  3. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Physician defined. 725.703 Section 725.703... defined. The term “physician” includes only doctors of medicine (MD) and osteopathic practitioners within the scope of their practices as defined by State law. No treatment or medical services performed...

  4. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  5. 20 CFR 404.429 - Earnings; defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Earnings; defined. 404.429 Section 404.429...- ) Deductions; Reductions; and Nonpayments of Benefits § 404.429 Earnings; defined. (a) General. The term... purpose of the earnings test under this subpart: (i) If you reach full retirement age, as defined in §...

  6. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  7. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Physician defined. 725.703 Section 725.703... AND HEALTH ACT, AS AMENDED Medical Benefits and Vocational Rehabilitation § 725.703 Physician defined... scope of their practices as defined by State law. No treatment or medical services performed by...

  8. A Preliminary Study of Psychiatric, Familial, and Medical Characteristics of High Utilizing Sickle Cell Disease Patients

    PubMed Central

    Carroll, C. Patrick; Haywood, Carlton; Hoot, Michelle R.; Lanzkron, Sophie

    2012-01-01

    Objectives To identify demographic, medical, and psychosocial characteristics that distinguished sickle cell disease patients who were frequent utilizers of urgent or emergent care resources from low-utilizing patients. Methods Patients at a large urban comprehensive sickle cell disease treatment center were recruited from clinic or during urgent care visits. Participants who were high utilizers, defined as having more than 4 acute or emergency care visits in the prior 12 months, were compared to patients with more typical utilization patterns on lifetime complications of SCD, family background, psychiatric history, occupational function, coping, depressive symptoms, and personality. Results High utilizers were nearly a decade younger on average; despite this they had a similar lifetime history of SCD complications. High utilizing patients' parents appeared to have greater educational achievement overall. High utilizers reported a nearly three-fold greater prevalence of psychiatric illness in family members than low utilizers. On other measures; including coping strategies, social support, and personality; the two groups were comparable. Discussion The study strengthens emerging evidence that disease severity, familial factors related to greater parental education, and psychiatric illness are important factors in high care utilization in patients with sickle cell disease. PMID:23246997

  9. Low Circulating Levels of IGF-1 in Healthy Adults Are Associated With Reduced β-Cell Function, Increased Intramyocellular Lipid, and Enhanced Fat Utilization During Fasting

    PubMed Central

    Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M. Loredana; Sleigh, Alison; Jørgensen, Sine Wanda; Hill, Nathan R.; Mooslehner, Katrin; Yeo, Giles S. H.; Bluck, Les; Juul, Anders; Vaag, Allan; Dunger, David B.

    2015-01-01

    important marker of β-cell function and glucose as well as lipid metabolic responses during fasting. PMID:24617714

  10. Functional Training Revisited.

    ERIC Educational Resources Information Center

    Siff, Mel C.

    2002-01-01

    Asserts that though functional training is vital in all sporting preparation, it is only one aspect of the overall process. The paper defines functional training; discusses facets of functionality, functionality and balancing drills, and functional training and periodization; and concludes that functionality is best defined in terms of the outcome…

  11. 10 CFR 205.375 - Guidelines defining inadequate fuel or energy supply.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Guidelines defining inadequate fuel or energy supply. 205.375 Section 205.375 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric... Electric Power § 205.375 Guidelines defining inadequate fuel or energy supply. An inadequate utility...

  12. 10 CFR 205.375 - Guidelines defining inadequate fuel or energy supply.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Guidelines defining inadequate fuel or energy supply. 205.375 Section 205.375 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric... Electric Power § 205.375 Guidelines defining inadequate fuel or energy supply. An inadequate utility...

  13. 10 CFR 205.375 - Guidelines defining inadequate fuel or energy supply.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Guidelines defining inadequate fuel or energy supply. 205.375 Section 205.375 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric... Electric Power § 205.375 Guidelines defining inadequate fuel or energy supply. An inadequate utility...

  14. 10 CFR 205.375 - Guidelines defining inadequate fuel or energy supply.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Guidelines defining inadequate fuel or energy supply. 205.375 Section 205.375 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric... Electric Power § 205.375 Guidelines defining inadequate fuel or energy supply. An inadequate utility...

  15. 10 CFR 205.375 - Guidelines defining inadequate fuel or energy supply.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Guidelines defining inadequate fuel or energy supply. 205.375 Section 205.375 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Electric... Electric Power § 205.375 Guidelines defining inadequate fuel or energy supply. An inadequate utility...

  16. Hardware Architecture Study for NASA's Space Software Defined Radios

    NASA Technical Reports Server (NTRS)

    Reinhart, Richard C.; Scardelletti, Maximilian C.; Mortensen, Dale J.; Kacpura, Thomas J.; Andro, Monty; Smith, Carl; Liebetreu, John

    2008-01-01

    This study defines a hardware architecture approach for software defined radios to enable commonality among NASA space missions. The architecture accommodates a range of reconfigurable processing technologies including general purpose processors, digital signal processors, field programmable gate arrays (FPGAs), and application-specific integrated circuits (ASICs) in addition to flexible and tunable radio frequency (RF) front-ends to satisfy varying mission requirements. The hardware architecture consists of modules, radio functions, and and interfaces. The modules are a logical division of common radio functions that comprise a typical communication radio. This paper describes the architecture details, module definitions, and the typical functions on each module as well as the module interfaces. Trade-offs between component-based, custom architecture and a functional-based, open architecture are described. The architecture does not specify the internal physical implementation within each module, nor does the architecture mandate the standards or ratings of the hardware used to construct the radios.

  17. Defining Known Drug Space Using DFT.

    PubMed

    Matuszek, Anna M; Reynisson, Jóhannes

    2016-02-01

    A density functional theory (DFT) study was performed on a collection of clinically approved drugs, or Known Drug Space (KDS), to determine the statistical distribution of four properties: dipole moment (DM), polarisability (POL), ionisation potential (IP) and electron affinity (EA). The DM and POL are linked to cell permeability of drugs whereas IP and EA reflect their redox stability thus ease of metabolism. A benchmarking exercise showed a good correlation between experimental values and their predicted counterparts. It was found that KDS occupies the volume of chemical space defined by: DM≤10 D, POL≤68 Å(3) , IP 6.0-9.0 V and EA-1.5-2.0 eV. Only 16 % of the drugs are outside one or more of these parameters. Three categories based on known oral absorption and bioavailability (low/medium/high) were established and compared. Predominately, drugs designated as 'low' were found outside the established parameters. The properties were compared with mainstream molecular descriptors and a strong correlation was seen for POL to MW (r(2) =0.899), which can explain the success of the latter since POL reflects the ability of molecules to interact with polar and non-polar environments such as water and interior of a membrane. PMID:27491789

  18. Defining Astrology in Ancient and Classical History

    NASA Astrophysics Data System (ADS)

    Campion, Nicholas

    2015-05-01

    Astrology in the ancient and classical worlds can be partly defined by its role, and partly by the way in which scholars spoke about it. The problem is complicated by the fact that the word is Greek - it has no Babylonian or Egyptian cognates - and even in Greece it was interchangeable with its cousin, 'astronomy'. Yet if we are to understand the role of the sky, stars and planets in culture, debates about the nature of ancient astrology, by both classical and modern scholars, must be taken into account. This talk will consider modern scholars' typologies of ancient astrology, together with ancient debates from Cicero in the 1st century BC, to Plotinus (204/5-270 AD) and Isidore of Seville (c. 560 - 4 April 636). It will consider the implications for our understanding of astronomy's role in culture, and conclude that in the classical period astrology may be best understood through its diversity and allegiance to competing philosophies, and that its functions were therefore similarly varied.

  19. Nramp defines a family of membrane proteins.

    PubMed Central

    Cellier, M; Privé, G; Belouchi, A; Kwan, T; Rodrigues, V; Chia, W; Gros, P

    1995-01-01

    Nramp (natural resistance-associated macrophage protein) is a newly identified family of integral membrane proteins whose biochemical function is unknown. We report on the identification of Nramp homologs from the fly Drosophila melanogaster, the plant Oryza sativa, and the yeast Saccharomyces cerevisiae. Optimal alignment of protein sequences required insertion of very few gaps and revealed remarkable sequence identity of 28% (yeast), 40% (plant), and 55% (fly) with the mammalian proteins (46%, 58%, and 73% similarity), as well as a common predicted transmembrane topology. This family is defined by a highly conserved hydrophobic core encoding 10 transmembrane segments. Other features of this hydrophobic core include several invariant charged residues, helical periodicity of sequence conservation suggesting conserved and nonconserved faces for several transmembrane helices, a consensus transport signature on the intracytoplasmic face of the membrane, and structural determinants previously described in ion channels. These characteristics suggest that the Nramp polypeptides form part of a group of transporters or channels that act on as yet unidentified substrates. Images Fig. 1 PMID:7479731

  20. Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state

    PubMed Central

    Rotem, Assaf; Ram, Oren; Shoresh, Noam; Sperling, Ralph A.; Goren, Alon; Weitz, David A.; Bernstein, Bradley E.

    2015-01-01

    Chromatin profiling provides a versatile means to investigate functional genomic elements and their regulation. However, current methods yield ensemble profiles that are insensitive to cell-to-cell variation. Here we combine microfluidics, DNA barcoding and sequencing to collect chromatin data at single-cell resolution. We demonstrate the utility of the technology by assaying thousands of individual cells, and using the data to deconvolute a mixture of ES cells, fibroblasts and hematopoietic progenitors into high-quality chromatin state maps for each cell type. The data from each single cell is sparse, comprising on the order of 1000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of sub-populations defined by differences in chromatin signatures of pluripotency and differentiation priming. We corroborate these findings by comparison to orthogonal single-cell gene expression data. Our method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone. PMID:26458175