Sample records for show mutually exclusive

  1. Role and convergent evolution of competing RNA secondary structures in mutually exclusive splicing

    PubMed Central

    Yue, Yuan; Hou, Shouqing; Wang, Xiu; Zhan, Leilei; Cao, Guozheng; Li, Guoli; Shi, Yang; Zhang, Peng; Hong, Weiling; Lin, Hao; Liu, Baoping; Shi, Feng; Yang, Yun; Jin, Yongfeng

    2017-01-01

    ABSTRACT Exon or cassette duplication is an important means of expanding protein and functional diversity through mutually exclusive splicing. However, the mechanistic basis of this process in non-arthropod species remains poorly understood. Here, we demonstrate that MRP1 genes underwent tandem exon duplication in Nematoda, Platyhelminthes, Annelida, Mollusca, Arthropoda, Echinodermata, and early-diverging Chordata but not in late-diverging vertebrates. Interestingly, these events were of independent origin in different phyla, suggesting convergent evolution of alternative splicing. Furthermore, we showed that multiple sets of clade-conserved RNA pairings evolved to guide species-specific mutually exclusive splicing in Arthropoda. Importantly, we also identified a similar structural code in MRP exon clusters of the annelid, Capitella teleta, and chordate, Branchiostoma belcheri, suggesting an evolutionarily conserved competing pairing-guided mechanism in bilaterians. Taken together, these data reveal the molecular determinants and RNA pairing-guided evolution of species-specific mutually exclusive splicing spanning more than 600 million years of bilaterian evolution. These findings have a significant impact on our understanding of the evolution of and mechanism underpinning isoform diversity and complex gene structure. PMID:28277933

  2. Role and convergent evolution of competing RNA secondary structures in mutually exclusive splicing.

    PubMed

    Yue, Yuan; Hou, Shouqing; Wang, Xiu; Zhan, Leilei; Cao, Guozheng; Li, Guoli; Shi, Yang; Zhang, Peng; Hong, Weiling; Lin, Hao; Liu, Baoping; Shi, Feng; Yang, Yun; Jin, Yongfeng

    2017-10-03

    Exon or cassette duplication is an important means of expanding protein and functional diversity through mutually exclusive splicing. However, the mechanistic basis of this process in non-arthropod species remains poorly understood. Here, we demonstrate that MRP1 genes underwent tandem exon duplication in Nematoda, Platyhelminthes, Annelida, Mollusca, Arthropoda, Echinodermata, and early-diverging Chordata but not in late-diverging vertebrates. Interestingly, these events were of independent origin in different phyla, suggesting convergent evolution of alternative splicing. Furthermore, we showed that multiple sets of clade-conserved RNA pairings evolved to guide species-specific mutually exclusive splicing in Arthropoda. Importantly, we also identified a similar structural code in MRP exon clusters of the annelid, Capitella teleta, and chordate, Branchiostoma belcheri, suggesting an evolutionarily conserved competing pairing-guided mechanism in bilaterians. Taken together, these data reveal the molecular determinants and RNA pairing-guided evolution of species-specific mutually exclusive splicing spanning more than 600 million years of bilaterian evolution. These findings have a significant impact on our understanding of the evolution of and mechanism underpinning isoform diversity and complex gene structure.

  3. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... 90.165 Section 90.165 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Governing Facilities Used to Provide Commercial Mobile Radio Services § 90.165 Procedures for mutually exclusive applications. Mutually exclusive commercial mobile radio service applications are processed in...

  4. 47 CFR 22.131 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES PUBLIC MOBILE SERVICES Licensing Requirements and Procedures Applications and Notifications § 22... procedures in this section for processing mutually exclusive applications in the Public Mobile Services... 47 Telecommunication 2 2010-10-01 2010-10-01 false Procedures for mutually exclusive applications...

  5. 47 CFR 101.51 - Comparative evaluation of mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Comparative evaluation of mutually exclusive....51 Comparative evaluation of mutually exclusive applications. (a) In order to expedite action on... this section if: (1) The applications are entitled to comparative consideration pursuant to § 101.45...

  6. 47 CFR 101.51 - Comparative evaluation of mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Comparative evaluation of mutually exclusive....51 Comparative evaluation of mutually exclusive applications. (a) In order to expedite action on... this section if: (1) The applications are entitled to comparative consideration pursuant to § 101.45...

  7. 47 CFR 101.51 - Comparative evaluation of mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Comparative evaluation of mutually exclusive....51 Comparative evaluation of mutually exclusive applications. (a) In order to expedite action on... this section if: (1) The applications are entitled to comparative consideration pursuant to § 101.45...

  8. 47 CFR 101.51 - Comparative evaluation of mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Comparative evaluation of mutually exclusive....51 Comparative evaluation of mutually exclusive applications. (a) In order to expedite action on... this section if: (1) The applications are entitled to comparative consideration pursuant to § 101.45...

  9. 47 CFR 101.51 - Comparative evaluation of mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Comparative evaluation of mutually exclusive....51 Comparative evaluation of mutually exclusive applications. (a) In order to expedite action on... this section if: (1) The applications are entitled to comparative consideration pursuant to § 101.45...

  10. The Role of Novelty in Early Word Learning

    ERIC Educational Resources Information Center

    Mather, Emily; Plunkett, Kim

    2012-01-01

    What mechanism implements the mutual exclusivity bias to map novel labels to objects without names? Prominent theoretical accounts of mutual exclusivity (e.g., Markman, 1989, 1990) propose that infants are guided by their knowledge of object names. However, the mutual exclusivity constraint could be implemented via monitoring of object novelty…

  11. Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.

    PubMed

    Pandith, Arshad A; Hussain, Aashaq; Khan, Mosin S; Shah, Zafar A; Wani, M Saleem; Siddiqi, Mushtaq A

    2016-01-01

    Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

  12. The Role of Gaze Direction and Mutual Exclusivity in Guiding 24-Month-Olds' Word Mappings

    ERIC Educational Resources Information Center

    Graham, Susan A.; Nilsen, Elizabeth S.; Collins, Sarah; Olineck, Kara

    2010-01-01

    In these studies, we examined how a default assumption about word meaning, the mutual exclusivity assumption and an intentional cue, gaze direction, interacted to guide 24-month-olds' object-word mappings. In Expt 1, when the experimenter's gaze was consistent with the mutual exclusivity assumption, novel word mappings were facilitated. When the…

  13. Learning Words over Time: The Role of Stimulus Repetition in Mutual Exclusivity

    ERIC Educational Resources Information Center

    Mather, Emily; Plunkett, Kim

    2009-01-01

    During the second year of life, infants develop a preference to attach novel labels to novel objects. This behavior is commonly known as "mutual exclusivity" (Markman, 1989). In an intermodal preferential looking experiment with 19.5- and 22.5-month-olds, stimulus repetition was critical for observing mutual exclusivity. On the first…

  14. Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

    PubMed Central

    Venereau, Emilie; Casalgrandi, Maura; Schiraldi, Milena; Antoine, Daniel J.; Cattaneo, Angela; De Marchis, Francesco; Liu, Jaron; Antonelli, Antonella; Preti, Alessandro; Raeli, Lorenzo; Shams, Sara Samadi; Yang, Huan; Varani, Luca; Andersson, Ulf; Tracey, Kevin J.; Bachi, Angela; Uguccioni, Mariagrazia

    2012-01-01

    Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to sulfonates by reactive oxygen species abrogates both activities. We show that leukocyte recruitment and activation can be separated. A nonoxidizable HMGB1 mutant in which serines replace all cysteines (3S-HMGB1) does not promote cytokine production, but is more effective than wild-type HMGB1 in recruiting leukocytes in vivo. BoxA, a HMGB1 inhibitor, interferes with leukocyte recruitment but not with activation. We detected the different redox forms of HMGB1 ex vivo within injured muscle. HMGB1 is completely reduced at first and disulfide-bonded later. Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states. PMID:22869893

  15. Propagating Resource Constraints Using Mutual Exclusion Reasoning

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy; Sanchez, Romeo; Do, Minh B.; Clancy, Daniel (Technical Monitor)

    2001-01-01

    One of the most recent techniques for propagating resource constraints in Constraint Based scheduling is Energy Constraint. This technique focuses in precedence based scheduling, where precedence relations are taken into account rather than the absolute position of activities. Although, this particular technique proved to be efficient on discrete unary resources, it provides only loose bounds for jobs using discrete multi-capacity resources. In this paper we show how mutual exclusion reasoning can be used to propagate time bounds for activities using discrete resources. We show that our technique based on critical path analysis and mutex reasoning is just as effective on unary resources, and also shows that it is more effective on multi-capacity resources, through both examples and empirical study.

  16. 12 CFR 223.24 - What valuation principles apply to extensions of credit secured by affiliate securities?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... paragraphs (f)(1) and (5) of § 223.42. (c) Exclusion of eligible affiliated mutual fund securities—(1) The exclusion. Eligible affiliated mutual fund securities are not considered to be securities issued by an... extension of credit will be used to purchase the eligible affiliated mutual fund securities collateral or...

  17. 12 CFR 223.24 - What valuation principles apply to extensions of credit secured by affiliate securities?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... paragraphs (f)(1) and (5) of § 223.42. (c) Exclusion of eligible affiliated mutual fund securities—(1) The exclusion. Eligible affiliated mutual fund securities are not considered to be securities issued by an... extension of credit will be used to purchase the eligible affiliated mutual fund securities collateral or...

  18. Decision Making for Healthcare Resource Allocation: Joint v. Separate Decisions on Interacting Interventions.

    PubMed

    Dakin, Helen; Gray, Alastair

    2018-05-01

    Standard guidance for allocating healthcare resources based on cost-effectiveness recommends using different decision rules for independent and mutually exclusive alternatives, although there is some confusion around the definition of "mutually exclusive." This paper reviews the definitions used in the literature and shows that interactions (i.e., non-additive effects, whereby the effect of giving 2 interventions simultaneously does not equal the sum of their individual effects) are the defining feature of mutually exclusive alternatives: treatments cannot be considered independent if the costs and/or benefits of one treatment are affected by the other treatment. The paper then identifies and categorizes the situations in which interventions are likely to have non-additive effects, including interventions targeting the same goal or clinical event, or life-saving interventions given to overlapping populations. We demonstrate that making separate decisions on interventions that have non-additive effects can prevent us from maximizing health gained from the healthcare budget. In contrast, treating combinations of independent options as though they were "mutually exclusive" makes the analysis more complicated but does not affect the conclusions. Although interactions are considered by the World Health Organization, other decision makers, such as the National Institute for Health and Care Excellence (NICE), currently make independent decisions on treatments likely to have non-additive effects. We propose a framework by which interactions could be considered when selecting, prioritizing, and appraising healthcare technologies to ensure efficient, evidence-based decision making.

  19. A weighted exact test for mutually exclusive mutations in cancer

    PubMed Central

    Leiserson, Mark D.M.; Reyna, Matthew A.; Raphael, Benjamin J.

    2016-01-01

    Motivation: The somatic mutations in the pathways that drive cancer development tend to be mutually exclusive across tumors, providing a signal for distinguishing driver mutations from a larger number of random passenger mutations. This mutual exclusivity signal can be confounded by high and highly variable mutation rates across a cohort of samples. Current statistical tests for exclusivity that incorporate both per-gene and per-sample mutational frequencies are computationally expensive and have limited precision. Results: We formulate a weighted exact test for assessing the significance of mutual exclusivity in an arbitrary number of mutational events. Our test conditions on the number of samples with a mutation as well as per-event, per-sample mutation probabilities. We provide a recursive formula to compute P-values for the weighted test exactly as well as a highly accurate and efficient saddlepoint approximation of the test. We use our test to approximate a commonly used permutation test for exclusivity that conditions on per-event, per-sample mutation frequencies. However, our test is more efficient and it recovers more significant results than the permutation test. We use our Weighted Exclusivity Test (WExT) software to analyze hundreds of colorectal and endometrial samples from The Cancer Genome Atlas, which are two cancer types that often have extremely high mutation rates. On both cancer types, the weighted test identifies sets of mutually exclusive mutations in cancer genes with fewer false positives than earlier approaches. Availability and Implementation: See http://compbio.cs.brown.edu/projects/wext for software. Contact: braphael@cs.brown.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27587696

  20. A Study of Shared-Memory Mutual Exclusion Protocols Using CADP

    NASA Astrophysics Data System (ADS)

    Mateescu, Radu; Serwe, Wendelin

    Mutual exclusion protocols are an essential building block of concurrent systems: indeed, such a protocol is required whenever a shared resource has to be protected against concurrent non-atomic accesses. Hence, many variants of mutual exclusion protocols exist in the shared-memory setting, such as Peterson's or Dekker's well-known protocols. Although the functional correctness of these protocols has been studied extensively, relatively little attention has been paid to their non-functional aspects, such as their performance in the long run. In this paper, we report on experiments with the performance evaluation of mutual exclusion protocols using Interactive Markov Chains. Steady-state analysis provides an additional criterion for comparing protocols, which complements the verification of their functional properties. We also carefully re-examined the functional properties, whose accurate formulation as temporal logic formulas in the action-based setting turns out to be quite involved.

  1. Send-side matching of data communications messages

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-07-01

    Send-side matching of data communications messages includes a plurality of compute nodes organized for collective operations, including: issuing by a receiving node to source nodes a receive message that specifies receipt of a single message to be sent from any source node, the receive message including message matching information, a specification of a hardware-level mutual exclusion device, and an identification of a receive buffer; matching by two or more of the source nodes the receive message with pending send messages in the two or more source nodes; operating by one of the source nodes having a matching send message the mutual exclusion device, excluding messages from other source nodes with matching send messages and identifying to the receiving node the source node operating the mutual exclusion device; and sending to the receiving node from the source node operating the mutual exclusion device a matched pending message.

  2. Send-side matching of data communications messages

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-06-17

    Send-side matching of data communications messages in a distributed computing system comprising a plurality of compute nodes, including: issuing by a receiving node to source nodes a receive message that specifies receipt of a single message to be sent from any source node, the receive message including message matching information, a specification of a hardware-level mutual exclusion device, and an identification of a receive buffer; matching by two or more of the source nodes the receive message with pending send messages in the two or more source nodes; operating by one of the source nodes having a matching send message the mutual exclusion device, excluding messages from other source nodes with matching send messages and identifying to the receiving node the source node operating the mutual exclusion device; and sending to the receiving node from the source node operating the mutual exclusion device a matched pending message.

  3. 47 CFR 22.509 - Procedures for mutually exclusive applications in the Paging and Radiotelephone Service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... facilities on the same channel in the same area, or the technical proposals are otherwise in conflict. See... all later-filed mutually exclusive applications of any type in either service to be “cut off...

  4. 47 CFR 24.431 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Mutually exclusive applications. 24.431 Section 24.431 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... result in a material impairment to service rendered to the public despite full cooperation in good faith...

  5. 47 CFR 24.431 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Mutually exclusive applications. 24.431 Section 24.431 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... result in a material impairment to service rendered to the public despite full cooperation in good faith...

  6. Multistability with a Metastable Mixed State

    NASA Astrophysics Data System (ADS)

    Sneppen, Kim; Mitarai, Namiko

    2012-09-01

    Complex dynamical systems often show multiple metastable states. In macroevolution, such behavior is suggested by punctuated equilibrium and discrete geological epochs. In molecular biology, bistability is found in epigenetics and in the many mutually exclusive states that a human cell can take. Sociopolitical systems can be single-party regimes or a pluralism of balancing political fractions. To introduce multistability, we suggest a model system of D mutually exclusive microstates that battle for dominance in a large system. Assuming one common intermediate state, we obtain D+1 metastable macrostates for the system, one of which is a self-reinforced mixture of all D+1 microstates. Robustness of this metastable mixed state increases with diversity D.

  7. Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer

    PubMed Central

    Xue, Mengzhu; Liu, Haiyue; Zhang, Liwen; Chang, Hongyuan; Liu, Yuwei; Du, Shaowei; Yang, Yingqun; Wang, Peng

    2017-01-01

    Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis. PMID:28397780

  8. Mutually Exclusive Splicing of the Insect Dscam Pre-mRNA Directed by Competing Intronic RNA Secondary Structures

    PubMed Central

    Graveley, Brenton R.

    2008-01-01

    Summary Drosophila Dscam encodes 38,016 distinct axon guidance receptors through the mutually exclusive alternative splicing of 95 variable exons. Importantly, known mechanisms that ensure the mutually exclusive splicing of pairs of exons cannot explain this phenomenon in Dscam. I have identified two classes of conserved elements in the Dscam exon 6 cluster, which contains 48 alternative exons—the docking site, located in the intron downstream of constitutive exon 5, and the selector sequences, which are located upstream of each exon 6 variant. Strikingly, each selector sequence is complementary to a portion of the docking site, and this pairing juxtaposes one, and only one, alternative exon to the upstream constitutive exon. The mutually exclusive nature of the docking site:selector sequence interactions suggests that the formation of these competing RNA structures is a central component of the mechanism guaranteeing that only one exon 6 variant is included in each Dscam mRNA. PMID:16213213

  9. Long-range RNA pairings contribute to mutually exclusive splicing

    PubMed Central

    Yue, Yuan; Yang, Yun; Dai, Lanzhi; Cao, Guozheng; Chen, Ran; Hong, Weiling; Liu, Baoping; Shi, Yang; Meng, Yijun; Shi, Feng; Xiao, Mu; Jin, Yongfeng

    2016-01-01

    Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA–RNA interactions in gene regulatory networks. PMID:26554032

  10. Long-range RNA pairings contribute to mutually exclusive splicing.

    PubMed

    Yue, Yuan; Yang, Yun; Dai, Lanzhi; Cao, Guozheng; Chen, Ran; Hong, Weiling; Liu, Baoping; Shi, Yang; Meng, Yijun; Shi, Feng; Xiao, Mu; Jin, Yongfeng

    2016-01-01

    Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons. Moreover, we demonstrate that the splicing outcome of alternative exons is mediated in relative pairing strength-correlated mode. Combined comparative genomics analysis and experimental evidence revealed similar bidirectional structural architectures in exon clusters 4 and 9 of the Dscam gene. Our findings provide a novel mechanistic framework for the regulation of mutually exclusive splicing and may offer potentially applicable insights into long-range RNA-RNA interactions in gene regulatory networks. © 2015 Yue et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  11. Representing Mutually Exclusive Knowledge in a Property Hierarchy for a Reasoning System in Clinical Gynecology

    PubMed Central

    Small, Steven L.; Muechler, Eberhard K.

    1985-01-01

    The education and practice of clinical medicine can benefit significantly from the use of computational assistants. This article describes the development of a prototype system called SURGES (Strong/University of Rochester Gynecological Expert System) for representing medical knowledge and then applying this knowledge to suggest diagnostic procedures in medical gynecology. The paper focuses on the representation technique of property inheritance, which facilitates the simple common sense reasoning required to enable execution of the more complex medical inferences. Such common sense can be viewed as a collection mundane inferences, which are the simple conclusions drawn from knowledge that an exclusive or (XOR) relation (i.e., mutual exclusion) holds among a number of facts. The paper discusses the use of a property hierarchy for this purpose and shows how it simplifies knowledge representation in medical artificial intelligence (AIM) computer systems.

  12. 47 CFR 22.509 - Procedures for mutually exclusive applications in the Paging and Radiotelephone Service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Procedures for mutually exclusive applications in the Paging and Radiotelephone Service. 22.509 Section 22.509 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone...

  13. 47 CFR 22.509 - Procedures for mutually exclusive applications in the Paging and Radiotelephone Service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Procedures for mutually exclusive applications in the Paging and Radiotelephone Service. 22.509 Section 22.509 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone...

  14. 47 CFR 22.509 - Procedures for mutually exclusive applications in the Paging and Radiotelephone Service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Procedures for mutually exclusive applications in the Paging and Radiotelephone Service. 22.509 Section 22.509 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Paging and Radiotelephone...

  15. 47 CFR 73.7001 - Services subject to evaluation by point system.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... evaluate mutually exclusive applications for new radio, television, and FM translator facilities, and for... mutually exclusive applications for new radio, television, and FM translator facilities, and for major... television translator and low power television facilities, and for major changes to existing facilities, only...

  16. Mutual Exclusion of Urea and Trimethylamine N-oxide from Amino Acids in Mixed Solvent Environment

    NASA Astrophysics Data System (ADS)

    Ganguly, Pritam; Hajari, Timir; Shea, Joan-Emma; van der Vegt, Nico F. A.

    2015-03-01

    We study the solvation thermodynamics of individual amino acids in mixed urea and trimethylamine N-oxide (TMAO) solutions using molecular dynamics simulations and the Kirkwood-Buff theory. Our results on the preferential interactions between the amino acids and the cosolvents (urea and TMAO) show a mutual exclusion of both the cosolvents from the amino acid surface in the mixed cosolvent condition which is followed by an increase in the cosolvent-cosolvent aggregation away from the amino acid surface. The effects of the mixed cosolvents on the association of the amino acids and the preferential solvation of the amino acids by water are found to be highly non-linear in terms of the effects of the individual cosolvents. A similar result has been found for the association of the protein backbone, mimicked by triglycine. Our results have been confirmed by different TMAO force-fields and the mutual exclusions of the cosolvents from the amino acids are found to be independent of the choice of the strength of the TMAO-water interactions. Based on our data, a general mechanism can potentially be proposed for the effects of the mixed cosolvents on the preferential solvations of the solutes including the case of cononsolvency.

  17. Introducing Disjoint and Independent Events in Probability.

    ERIC Educational Resources Information Center

    Kelly, I. W.; Zwiers, F. W.

    Two central concepts in probability theory are those of independence and mutually exclusive events. This document is intended to provide suggestions to teachers that can be used to equip students with an intuitive, comprehensive understanding of these basic concepts in probability. The first section of the paper delineates mutually exclusive and…

  18. Mutually Exclusive, Complementary, or . . .

    ERIC Educational Resources Information Center

    Schloemer, Cathy G.

    2016-01-01

    Whether students are beginning their study of probability or are well into it, distinctions between complementary sets and mutually exclusive sets can be confusing. Cathy Schloemer writes in this article that for years she used typical classroom examples but was not happy with the student engagement or the level of understanding they produced.…

  19. 47 CFR 22.717 - Procedure for mutually exclusive applications in the Rural Radiotelephone Service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Procedure for mutually exclusive applications in the Rural Radiotelephone Service. 22.717 Section 22.717 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Rural Radiotelephone Service § 22.717...

  20. 47 CFR 22.717 - Procedure for mutually exclusive applications in the Rural Radiotelephone Service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Procedure for mutually exclusive applications in the Rural Radiotelephone Service. 22.717 Section 22.717 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Rural Radiotelephone Service § 22.717...

  1. 47 CFR 22.717 - Procedure for mutually exclusive applications in the Rural Radiotelephone Service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Procedure for mutually exclusive applications in the Rural Radiotelephone Service. 22.717 Section 22.717 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Rural Radiotelephone Service § 22.717...

  2. On Whether People Have the Capacity to Make Observations of Mutually Excl usive Physical Phenomena Simultaneously

    NASA Astrophysics Data System (ADS)

    Snyder

    1998-04-01

    It has been shown by Einstein, Podolsky, and Rosen that in quantum mechanics two different wave functions can simultaneously characterize the same physical existent. This result means that one can make predictions regarding simultaneous, mutually exclusive features of a physical existent. It is important to ask whether people have the capacity to make observations of mutually exclusive phenomena simultaneously? Our everyday experience informs us that a human observer is capable of observing only one set of physical circumstances at a time. Evidence from psychology, though, indicates that people indeed have the capacity to make observations of mutually exclusive phenomena simultaneously, even though this capacity is not generally recognized. Working independently, Sigmund Freud and William James provided some of this evidence. How the nature of the quantum mechanical wave function is associated with the problem posed by Einstein, Podolsky, and Rosen, is addressed at the end of the paper.

  3. Flexible Use of Mutual Exclusivity in Word Learning

    ERIC Educational Resources Information Center

    Kalashnikova, Marina; Mattock, Karen; Monaghan, Padraic

    2016-01-01

    From an early age, children apply the mutual exclusivity (ME) assumption, demonstrating preference for one-to-one mappings between words and their referents. However, for the acquisition of referentially overlapping terms, ME use must be suspended. We test whether contextual cues to intended meaning, in the form of presence of a speaker, may be…

  4. 47 CFR 22.131 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... excluded by that grant, pursuant to § 1.945 of this chapter. (1) Selection methods. In selecting the... under § 1.945 of this chapter, either before or after employing selection procedures. (3) Type of filing... Commission may attempt to resolve the mutual exclusivity by facilitating a settlement between the applicants...

  5. Decision Making for Healthcare Resource Allocation: Joint v. Separate Decisions on Interacting Interventions

    PubMed Central

    Dakin, Helen; Gray, Alastair

    2018-01-01

    Standard guidance for allocating healthcare resources based on cost-effectiveness recommends using different decision rules for independent and mutually exclusive alternatives, although there is some confusion around the definition of “mutually exclusive.” This paper reviews the definitions used in the literature and shows that interactions (i.e., non-additive effects, whereby the effect of giving 2 interventions simultaneously does not equal the sum of their individual effects) are the defining feature of mutually exclusive alternatives: treatments cannot be considered independent if the costs and/or benefits of one treatment are affected by the other treatment. The paper then identifies and categorizes the situations in which interventions are likely to have non-additive effects, including interventions targeting the same goal or clinical event, or life-saving interventions given to overlapping populations. We demonstrate that making separate decisions on interventions that have non-additive effects can prevent us from maximizing health gained from the healthcare budget. In contrast, treating combinations of independent options as though they were “mutually exclusive” makes the analysis more complicated but does not affect the conclusions. Although interactions are considered by the World Health Organization, other decision makers, such as the National Institute for Health and Care Excellence (NICE), currently make independent decisions on treatments likely to have non-additive effects. We propose a framework by which interactions could be considered when selecting, prioritizing, and appraising healthcare technologies to ensure efficient, evidence-based decision making. PMID:29683792

  6. Mutual Exclusivity Develops as a Consequence of Abstract Rather than Particular Vocabulary Knowledge

    ERIC Educational Resources Information Center

    Kalashnikova, Marina; Mattock, Karen; Monaghan, Padraic

    2016-01-01

    Mutual exclusivity (ME) refers to the assumption that there are one-to-one relations between linguistic forms and their meanings. It is used as a word-learning strategy whereby children tend to map novel labels to unfamiliar rather than familiar referents. Previous research has indicated a relation between ME and vocabulary development, which…

  7. 47 CFR 73.5002 - Application and certification procedures; return of mutually exclusive applications not subject...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... broadcast service auctions, or to apply for a noncommercial educational station, as described in 47 U.S.C... engineering data contained in the appropriate FCC form (FCC Form 301, FCC Form 346, or FCC Form 349... permitted to resolve their mutual exclusivities by making amendments to their engineering submissions...

  8. Children's Use of Mutual Exclusivity to Learn Labels for Parts of Objects

    ERIC Educational Resources Information Center

    Hansen, Mikkel B.; Markman, Ellen M.

    2009-01-01

    When teaching children part terms, adults frequently outline the relevant part rather than simply point. This pragmatic information very likely helps children interpret the label correctly. But the importance of gestures may not negate the need for default lexical biases such as the whole object assumption and mutual exclusivity. On this view,…

  9. Juxtaposed genes in 7q21-22 amplicon contribute for two major gastric cancer sub-Types by mutual exclusive expression.

    PubMed

    Tamilzhalagan, Sembulingam; Muthuswami, Muthulakshmi; Ganesan, Kumaresan

    2017-04-01

    Genomic Copy Number Variations (CNV) and the associated gene signatures are useful for cancer prognosis, diagnosis, and targeted therapeutics. Earlier, 7q21-22 region was reported for frequent amplification in gastric cancer and potential candidate genes were identified. An analysis of the expression pattern of the 159 genes located in this amplicon revealed the consistent elevated expression of 21 genes in gastric tumors. These genes are closely arranged within the 20 Mb region, and they showed a bimodal expression pattern. SHFM1 and 14 other genes are expressed in intestinal type gastric tumors. COL1A2 and PCOLCE genes of this region are expressed in diffuse type gastric tumors. Similarly, genome-wide expression neighbors of SHFM1 and COL1A2 also showed mutually exclusive expression pattern, and stratify intestinal and diffuse type gastric tumors. The expression of COL1A2 gene-set is associated with poor prognosis, whereas the SHFM1 gene-set is associated with better prognosis among the gastric cancer patients. Despite being physical neighbors, the SHFM1 and COL1A2 genes express differentially in the two major clinical sub-types of gastric cancer in a mutually exclusive manner. The tight gene regulations operating between these juxtaposed genes deserve investigation to understand the molecular regulatory switch defining the determinants of the gastric cancer sub-types. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Supersymmetric black holes and Freudenthal duality

    NASA Astrophysics Data System (ADS)

    Marrani, Alessio; Mandal, Taniya; Tripathy, Prasanta K.

    2017-07-01

    We study the effect of Freudenthal duality on supersymmetric extremal black hole attractors in 𝒩 = 2, D = 4 ungauged supergravity. Freudenthal duality acts on the dyonic black hole charges as an anti-involution which keeps the black hole entropy and the critical points of the effective black hole potential invariant. We analyze its effect on the recently discovered distinct, mutually exclusive phases of axionic supersymmetric black holes, related to the existence of nontrivial involutory constant matrices. In particular, we consider a supersymmetric D0 - D4 - D6 black hole and we explicitly Freudenthal-map it to a supersymmetric D0 - D2 - D4 - D6 black hole. We thus show that the charge representation space of a supersymmetric D0 - D2 - D4 - D6 black hole also contains mutually exclusive domains.

  11. Kassiopeia: a database and web application for the analysis of mutually exclusive exomes of eukaryotes

    PubMed Central

    2014-01-01

    Background Alternative splicing is an important process in higher eukaryotes that allows obtaining several transcripts from one gene. A specific case of alternative splicing is mutually exclusive splicing, in which exactly one exon out of a cluster of neighbouring exons is spliced into the mature transcript. Recently, a new algorithm for the prediction of these exons has been developed based on the preconditions that the exons of the cluster have similar lengths, sequence homology, and conserved splice sites, and that they are translated in the same reading frame. Description In this contribution we introduce Kassiopeia, a database and web application for the generation, storage, and presentation of genome-wide analyses of mutually exclusive exomes. Currently, Kassiopeia provides access to the mutually exclusive exomes of twelve Drosophila species, the thale cress Arabidopsis thaliana, the flatworm Caenorhabditis elegans, and human. Mutually exclusive spliced exons (MXEs) were predicted based on gene reconstructions from Scipio. Based on the standard prediction values, with which 83.5% of the annotated MXEs of Drosophila melanogaster were reconstructed, the exomes contain surprisingly more MXEs than previously supposed and identified. The user can search Kassiopeia using BLAST or browse the genes of each species optionally adjusting the parameters used for the prediction to reveal more divergent or only very similar exon candidates. Conclusions We developed a pipeline to predict MXEs in the genomes of several model organisms and a web interface, Kassiopeia, for their visualization. For each gene Kassiopeia provides a comprehensive gene structure scheme, the sequences and predicted secondary structures of the MXEs, and, if available, further evidence for MXE candidates from cDNA/EST data, predictions of MXEs in homologous genes of closely related species, and RNA secondary structure predictions. Kassiopeia can be accessed at http://www.motorprotein.de/kassiopeia. PMID:24507667

  12. Identifying Driver Genomic Alterations in Cancers by Searching Minimum-Weight, Mutually Exclusive Sets

    PubMed Central

    Lu, Songjian; Lu, Kevin N.; Cheng, Shi-Yuan; Hu, Bo; Ma, Xiaojun; Nystrom, Nicholas; Lu, Xinghua

    2015-01-01

    An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms and the heterogeneity of cancers. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this characteristic has been utilized as an objective function to guide the search for driver mutations within a pathway. However, mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs. First, we identify the perturbed cellular signals by mining the gene expression data. Next, we search for a set of SGA events that carries strong information with respect to such perturbed signals while exhibiting mutual exclusivity. Finally, we design and implement an efficient exact algorithm to solve an NP-hard problem encountered in our approach. We apply this framework to the ovarian and glioblastoma tumor data available at the TCGA database, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways. PMID:26317392

  13. Enhanced Specification and Verification for Timed Planning

    DTIC Science & Technology

    2009-02-28

    Scheduling Problem The job-shop scheduling problem ( JSSP ) is a generic resource allocation problem in which common resources (“machines”) are required...interleaving of all processes Pi with the non-delay and mutual exclusion constraints: JSSP =̂ |||0<i6n Pi Where mutual-exclusion( JSSP ) For every complete...execution of JSSP (which terminates), its associated sched- ule S is a feasible schedule. An optimal schedule is a trace of JSSP with the minimum ending

  14. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component

    PubMed Central

    Shi, Hexin; Wang, Ying; Li, Xiaohong; Zhan, Xiaoming; Tan, Miao; Fina, Maggy; Su, Lijing; Pratt, David; Bu, Chun Hui; Hildebrand, Sara; Lyon, Stephen; Scott, Lindsay; Quan, Jiexia; Sun, Qihua; Russell, Jamie; Arnett, Stephanie; Jurek, Peter; Chen, Ding; Kravchenko, Vladimir V.; Mathison, John C.; Moresco, Eva Marie Y.; Monson, Nancy L.; Ulevitch, Richard J.; Beutler, Bruce

    2015-01-01

    The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines including IL-1β and IL-18. We show that NLRP3 inflammasome activation is restricted to interphase of the cell cycle by NEK7, a serine/threonine kinase previously implicated in mitosis. NLRP3 inflammasome activation requires NEK7, which binds to the NLRP3 leucine-rich repeat domain in a kinase-independent manner downstream from the induction of mitochondrial ROS. This interaction is necessary for NLRP3-ASC complex formation, ASC oligomerization, and caspase-1 activation. NEK7 promotes the NLRP3-dependent cellular inflammatory response to intraperitoneal monosodium urate challenge, and the development of experimental autoimmune encephalitis in mice. Our findings suggest NEK7 serves as a cellular switch that enforces mutual exclusivity between the inflammasome response and cell division. PMID:26642356

  15. Mutually Exclusive Formation of G-Quadruplex and i-Motif Is a General Phenomenon Governed by Steric Hindrance in Duplex DNA.

    PubMed

    Cui, Yunxi; Kong, Deming; Ghimire, Chiran; Xu, Cuixia; Mao, Hanbin

    2016-04-19

    G-Quadruplex and i-motif are tetraplex structures that may form in opposite strands at the same location of a duplex DNA. Recent discoveries have indicated that the two tetraplex structures can have conflicting biological activities, which poses a challenge for cells to coordinate. Here, by performing innovative population analysis on mechanical unfolding profiles of tetraplex structures in double-stranded DNA, we found that formations of G-quadruplex and i-motif in the two complementary strands are mutually exclusive in a variety of DNA templates, which include human telomere and promoter fragments of hINS and hTERT genes. To explain this behavior, we placed G-quadruplex- and i-motif-hosting sequences in an offset fashion in the two complementary telomeric DNA strands. We found simultaneous formation of the G-quadruplex and i-motif in opposite strands, suggesting that mutual exclusivity between the two tetraplexes is controlled by steric hindrance. This conclusion was corroborated in the BCL-2 promoter sequence, in which simultaneous formation of two tetraplexes was observed due to possible offset arrangements between G-quadruplex and i-motif in opposite strands. The mutual exclusivity revealed here sets a molecular basis for cells to efficiently coordinate opposite biological activities of G-quadruplex and i-motif at the same dsDNA location.

  16. Sliding of microtubules by a team of dynein motors: Understanding the effect of spatial distribution of motor tails and mutual exclusion of motor heads on microtubules

    NASA Astrophysics Data System (ADS)

    Singh, Hanumant Pratap; Takshak, Anjneya; Mall, Utkarsh; Kunwar, Ambarish

    2016-06-01

    Molecular motors are natural nanomachines that use the free energy released from ATP hydrolysis to generate mechanical forces. Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. These motors attach to a cargo microtubule via their tail domains, undergo the process of detachment and reattachment of their head domains on another track microtubule, while sliding the cargo microtubule along the track. Traditional continuum/mean-field approaches used in the past are not ideal for studying the sliding mechanism of microtubules, as they ignore spatial and temporal fluctuations due to different possible distributions of motor tails on cargo filament, as well as binding/unbinding of motors from their track. Therefore, these models cannot be used to address important questions such as how the distribution of motor tails on microtubules, or how the mutual exclusion of motor heads on microtubule tracks affects the sliding velocity of cargo microtubule. To answer these, here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distributions of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.

  17. The Logic of Reachability

    NASA Technical Reports Server (NTRS)

    Smith, David E.; Jonsson, Ari K.; Clancy, Daniel (Technical Monitor)

    2001-01-01

    In recent years, Graphplan style reachability analysis and mutual exclusion reasoning have been used in many high performance planning systems. While numerous refinements and extensions have been developed, the basic plan graph structure and reasoning mechanisms used in these systems are tied to the very simple STRIPS model of action. In 1999, Smith and Weld generalized the Graphplan methods for reachability and mutex reasoning to allow actions to have differing durations. However, the representation of actions still has some severe limitations that prevent the use of these techniques for many real-world planning systems. In this paper, we 1) separate the logic of reachability from the particular representation and inference methods used in Graphplan, and 2) extend the notions of reachability and mutual exclusion to more general notions of time and action. As it turns out, the general rules for mutual exclusion reasoning take on a remarkably clean and simple form. However, practical instantiations of them turn out to be messy, and require that we make representation and reasoning choices.

  18. Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable.

    PubMed

    Suda, Tetsuji; Yoshihara, Mitsuyo; Nakamura, Yoshiyasu; Sekiguchi, Hironobu; Godai, Ten-I; Sugano, Nobuhiro; Tsuchida, Kazuhito; Shiozawa, Manabu; Sakuma, Yuji; Tsuchiya, Eiju; Kameda, Yoichi; Akaike, Makoto; Matsukuma, Shoichi; Miyagi, Yohei

    2011-07-01

    MDM4, a homolog of MDM2, is considered a key negative regulator of p53. Gene amplification of MDM4 has been identified in a variety of tumors. MDM2 or MDM4 gene amplification is only associated with the wild-type TP53 gene in retinoblastomas, thus the amplification of the two genes is mutually exclusive. Previously, we demonstrated that MDM2 amplification and TP53 alteration were not mutually exclusive in colorectal cancer, and we identified a subset of colorectal cancer patients without alterations in either the TP53 or the MDM2 gene. In this study, we investigated the gene amplification status of MDM4 in the same set of colorectal cancer cases. Unexpectedly, MDM4 amplification was rare, detected in only 1.4% (3 out of 211) of colorectal cancer cases. All the three gene-amplified tumors also harbored TP53-inactivating mutations. This contradicts the simple mutually exclusive relationship observed in retinoblastomas. Surprisingly, two of the three MDM4-amplified tumors also demonstrated MDM2 amplification. Paradoxically, the MDM4 protein levels were decreased in the tumor tissue of the gene-amplified cases compared with levels in the matched normal mucosa. We speculate that MDM4 might play a role in colorectal carcinogenesis that is not limited to negative regulation of p53 in combination with MDM2. The functional significance of MDM4 is still unclear and further studies are needed.

  19. Diversification through multitrait evolution in a coevolving interaction.

    PubMed

    Thompson, John N; Schwind, Christopher; Guimarães, Paulo R; Friberg, Magne

    2013-07-09

    Mutualisms between species are interactions in which reciprocal exploitation results in outcomes that are mutually beneficial. This reciprocal exploitation is evident in the more than a thousand plant species that are pollinated exclusively by insects specialized to lay their eggs in the flowers they pollinate. By pollinating each flower in which she lays eggs, an insect guarantees that her larval offspring have developing seeds on which to feed, whereas the plant gains a specialized pollinator at the cost of some seeds. These mutualisms are often reciprocally obligate, potentially driving not only ongoing coadaptation but also diversification. The lack of known intermediate stages in most of these mutualisms, however, makes it difficult to understand whether these interactions could have begun to diversify even before they became reciprocally obligate. Experimental studies of the incompletely obligate interactions between woodland star (Lithophragma; Saxifragaceae) plants and their pollinating floral parasites in the moth genus Greya (Prodoxidae) show that, as these lineages have diversified, the moths and plants have evolved in ways that maintain effective oviposition and pollination. Experimental assessment of pollination in divergent species and quantitative evaluation of time-lapse photographic sequences of pollination viewed on surgically manipulated flowers show that various combinations of traits are possible for maintaining the mutualism. The results suggest that at least some forms of mutualism can persist and even diversify when the interaction is not reciprocally obligate.

  20. HIV/Sexually Transmitted Infection Risk Behaviors in Delinquent Youth with Psychiatric Disorders: A Longitudinal Study

    ERIC Educational Resources Information Center

    Elkington, Katherine; Teplin, Linda A.; Mericle, Amy A.; Welty, Leah J.; Romero, Erin G.; Abram, Karen M.

    2008-01-01

    The effect of psychiatric disorders on human immunodeficiency virus/sexually transmitted infection (HIV/STI) risk behaviors in juvenile justice youths is examined. Prevalence, persistence and prediction are addressed among four mutually exclusive diagnostic groups and results show a high prevalence rate of many HIV/STI sexual risk behaviors that…

  1. Finding Mutual Exclusion Invariants in Temporal Planning Domains

    NASA Technical Reports Server (NTRS)

    Bernardini, Sara; Smith, David E.

    2011-01-01

    We present a technique for automatically extracting temporal mutual exclusion invariants from PDDL2.2 planning instances. We first identify a set of invariant candidates by inspecting the domain and then check these candidates against properties that assure invariance. If these properties are violated, we show that it is sometimes possible to refine a candidate by adding additional propositions and turn it into a real invariant. Our technique builds on other approaches to invariant synthesis presented in the literature, but departs from their limited focus on instantaneous discrete actions by addressing temporal and numeric domains. To deal with time, we formulate invariance conditions that account for both the entire structure of the operators (including the conditions, rather than just the effects) and the possible interactions between operators. As a result, we construct a technique that is not only capable of identifying invariants for temporal domains, but is also able to find a broader set of invariants for non-temporal domains than the previous techniques.

  2. Reconsolidation and extinction are dissociable and mutually exclusive processes: behavioral and molecular evidence.

    PubMed

    Merlo, Emiliano; Milton, Amy L; Goozée, Zara Y; Theobald, David E; Everitt, Barry J

    2014-02-12

    Memory persistence is critically influenced by retrieval. In rats, a single presentation of a conditioned fear stimulus induces memory reconsolidation and fear memory persistence, while repeated fear cue presentations result in loss of fear through extinction. These two opposite behavioral outcomes are operationally linked by the number of cue presentations at memory retrieval. However, the behavioral properties and mechanistic determinants of the transition have not yet been explored; in particular, whether reconsolidation and extinction processes coexist or are mutually exclusive, depending on the exposure to non-reinforced retrieval events. We characterized both behaviorally and molecularly the transition from reconsolidation to extinction of conditioned fear and showed that an increase in calcineurin (CaN) in the basolateral amygdala (BLA) supports the shift from fear maintenance to fear inhibition. Gradually increasing the extent of retrieval induces a gradual decrease in freezing responses to the conditioned stimulus and a gradual increase in amygdala CaN level. This newly synthesized CaN is required for the extinction, but not the reconsolidation, of conditioned fear. During the transition from reconsolidation to extinction, we have revealed an insensitive state of the fear memory where NMDA-type glutamate receptor agonist and antagonist drugs are unable either to modulate CaN levels in the BLA or alter the reconsolidation or extinction processes. Together, our data indicate both that reconsolidation and extinction are mutually exclusive processes and also reveal the presence of a transitional, or "limbo," state of the original memory between these two alternative outcomes of fear memory retrieval, when neither process is engaged.

  3. Breakdown of an ant-plant mutualism follows the loss of large herbivores from an African savanna.

    PubMed

    Palmer, Todd M; Stanton, Maureen L; Young, Truman P; Goheen, Jacob R; Pringle, Robert M; Karban, Richard

    2008-01-11

    Mutualisms are key components of biodiversity and ecosystem function, yet the forces maintaining them are poorly understood. We investigated the effects of removing large mammals on an ant-Acacia mutualism in an African savanna. Ten years of large-herbivore exclusion reduced the nectar and housing provided by plants to ants, increasing antagonistic behavior by a mutualistic ant associate and shifting competitive dominance within the plant-ant community from this nectar-dependent mutualist to an antagonistic species that does not depend on plant rewards. Trees occupied by this antagonist suffered increased attack by stem-boring beetles, grew more slowly, and experienced doubled mortality relative to trees occupied by the mutualistic ant. These results show that large mammals maintain cooperation within a widespread symbiosis and suggest complex cascading effects of megafaunal extinction.

  4. Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors.

    PubMed

    Wang, Y; Smallwood, P M; Cowan, M; Blesh, D; Lawler, A; Nathans, J

    1999-04-27

    This study examines the mechanism of mutually exclusive expression of the human X-linked red and green visual pigment genes in their respective cone photoreceptors by asking whether this expression pattern can be produced in a mammal that normally carries only a single X-linked visual pigment gene. To address this question, we generated transgenic mice that carry a single copy of a minimal human X chromosome visual pigment gene array in which the red and green pigment gene transcription units were replaced, respectively, by alkaline phosphatase and beta-galactosidase reporters. As determined by histochemical staining, the reporters are expressed exclusively in cone photoreceptor cells. In 20 transgenic mice carrying any one of three independent transgene insertion events, an average of 63% of expressing cones have alkaline phosphatase activity, 10% have beta-galactosidase activity, and 27% have activity for both reporters. Thus, mutually exclusive expression of red and green pigment transgenes can be achieved in a large fraction of cones in a dichromat mammal, suggesting a facile evolutionary path for the development of trichromacy after visual pigment gene duplication. These observations are consistent with a model of visual pigment expression in which stochastic pairing occurs between a locus control region and either the red or the green pigment gene promotor.

  5. Bilingualism Affects 9-Month-Old Infants' Expectations about How Words Refer to Kinds

    ERIC Educational Resources Information Center

    Byers-Heinlein, Krista

    2017-01-01

    Infants are precocious word learners, and seem to possess systematic expectations about how words refer to object kinds. For example, while monolingual infants show a one-to-one mapping bias (e.g. mutual exclusivity), expecting each object to have only one basic level label, previous research has shown that this is less robust in bi- and…

  6. Failure to Learn from Feedback underlies Word Learning Difficulties in Toddlers at Risk for Autism

    ERIC Educational Resources Information Center

    Bedford, R.; Gliga, T.; Frame, K.; Hudry, K.; Chandler, S.; Johnson, M. H.; Charman, T.

    2013-01-01

    Children's assignment of novel words to nameless objects, over objects whose names they know (mutual exclusivity; ME) has been described as a driving force for vocabulary acquisition. Despite their ability to use ME to fast-map words (Preissler & Carey, 2005), children with autism show impaired language acquisition. We aimed to address…

  7. Language Acquisition and Language Learning: A Plea for Syncretism.

    ERIC Educational Resources Information Center

    Higgs, Theodore V.

    1985-01-01

    Discusses the apparent opposition between the concepts of language learning and language acquisition in the context of adult second-language study. Proposes that these two concepts are mutually supportive, not mutually exclusive. Demonstrates how the implications of learning vs. acquisition can be integrated into a communicative…

  8. 47 CFR 22.717 - Procedure for mutually exclusive applications in the Rural Radiotelephone Service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... channel in the same area, or the technical proposals are otherwise in conflict. See § 22.567. (b) A... exclusive applications of any type in either service to be “cut off” (excluded from a same-day filing group...

  9. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., the Commission may use competitive bidding, random selection, or comparative hearings, depending on... exclusive applications in a renewal filing group are designated for comparative consideration in a hearing... applications in the filing group for comparative consideration in a hearing. In this event, the result of the...

  10. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., the Commission may use competitive bidding, random selection, or comparative hearings, depending on... exclusive applications in a renewal filing group are designated for comparative consideration in a hearing... applications in the filing group for comparative consideration in a hearing. In this event, the result of the...

  11. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., the Commission may use competitive bidding, random selection, or comparative hearings, depending on... exclusive applications in a renewal filing group are designated for comparative consideration in a hearing... applications in the filing group for comparative consideration in a hearing. In this event, the result of the...

  12. A mutually exclusive stem–loop arrangement in roX2 RNA is essential for X-chromosome regulation in Drosophila

    PubMed Central

    Ilik, Ibrahim Avsar; Maticzka, Daniel; Georgiev, Plamen; Gutierrez, Noel Marie; Backofen, Rolf; Akhtar, Asifa

    2017-01-01

    The X chromosome provides an ideal model system to study the contribution of RNA–protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity purification) methodology, which provides unprecedented information about RNA secondary structures in vivo, we identified the minimal functional unit of roX2 RNA. By using wild-type and various MLE mutant derivatives, including a catalytically inactive MLE derivative, MLEGET, we show that the minimal roX RNA contains two mutually exclusive stem–loops that exist in a peculiar structural arrangement: When one stem–loop is unwound by MLE, an alternate structure can form, likely trapping MLE in this perpetually structured region. We show that this functional unit is necessary for dosage compensation, as mutations that disrupt this formation lead to male lethality. Thus, we propose that roX2 lncRNA contains an MLE-dependent affinity switch to enable reversible interactions of the MSL complex to allow dosage compensation of the X chromosome. PMID:29066499

  13. Chemical ecology of obligate pollination mutualisms: testing the 'private channel' hypothesis in the Breynia-Epicephala association.

    PubMed

    Svensson, Glenn P; Okamoto, Tomoko; Kawakita, Atsushi; Goto, Ryutaro; Kato, Makoto

    2010-06-01

    *Obligate mutualisms involving actively pollinating seed predators are among the most remarkable insect-plant relationships known, yet almost nothing is known about the chemistry of pollinator attraction in these systems. The extreme species specificity observed in these mutualisms may be maintained by specific chemical compounds through 'private channels'. Here, we tested this hypothesis using the monoecious Breynia vitis-idaea and its host-specific Epicephala pollinator as a model. *Headspace samples were collected from both male and female flowers of the host. Gas chromatography with electroantennographic detection (GC-EAD), coupled gas chromatography-mass spectrometry, and olfactometer bioassays were used to identify the floral compounds acting as the pollinator attractant. *Male and female flowers of B. vitis-idaea produced similar sets of general floral compounds, but in different ratios, and male flowers emitted significantly more scent than female flowers. A mixture of 2-phenylethyl alcohol and 2-phenylacetonitrile, the two most abundant compounds in male flowers, was as attractive to female moths as the male flower sample, although the individual compounds were slightly less attractive when tested separately. *Data on the floral scent signals mediating obligate mutualisms involving active pollination are still very limited. We show that system-specific chemistry is not necessary for efficient host location by exclusive pollinators in these tightly coevolved mutualisms.

  14. Molecular Simulations of Mutually Exclusive Folding in a Two-Domain Protein Switch

    PubMed Central

    Mills, Brandon M.; Chong, Lillian T.

    2011-01-01

    A major challenge with testing designs of protein conformational switches is the need for experimental probes that can independently monitor their individual protein domains. One way to circumvent this issue is to use a molecular simulation approach in which each domain can be directly observed. Here we report what we believe to be the first molecular simulations of mutually exclusive folding in an engineered two-domain protein switch, providing a direct view of how folding of one protein drives unfolding of the other in a barnase-ubiquitin fusion protein. These simulations successfully capture the experimental effects of interdomain linker length and ligand binding on the extent of unfolding in the less stable domain. In addition, the effect of linker length on the potential for oligomerization, which eliminates switch activity, is in qualitative agreement with analytical ultracentrifugation experiments. We also perform what we believe to be the first study of protein unfolding via progressive localized compression. Finally, we are able to explore the kinetics of mutually exclusive folding by determining the effect of linker length on rates of unfolding and refolding of each protein domain. Our results demonstrate that molecular simulations can provide seemingly novel biological insights on the behavior of individual protein domains, thereby aiding in the rational design of bifunctional switches. PMID:21281591

  15. A nutrient dependant switch explains mutually exclusive existence of meiosis and mitosis initiation in budding yeast.

    PubMed

    Wannige, C T; Kulasiri, D; Samarasinghe, S

    2014-01-21

    Nutrients from living environment are vital for the survival and growth of any organism. Budding yeast diploid cells decide to grow by mitosis type cell division or decide to create unique, stress resistant spores by meiosis type cell division depending on the available nutrient conditions. To gain a molecular systems level understanding of the nutrient dependant switching between meiosis and mitosis initiation in diploid cells of budding yeast, we develop a theoretical model based on ordinary differential equations (ODEs) including the mitosis initiator and its relations to budding yeast meiosis initiation network. Our model accurately and qualitatively predicts the experimentally revealed temporal variations of related proteins under different nutrient conditions as well as the diverse mutant studies related to meiosis and mitosis initiation. Using this model, we show how the meiosis and mitosis initiators form an all-or-none type bistable switch in response to available nutrient level (mainly nitrogen). The transitions to and from meiosis or mitosis initiation states occur via saddle node bifurcation. This bidirectional switch helps the optimal usage of available nutrients and explains the mutually exclusive existence of meiosis and mitosis pathways. © 2013 Elsevier Ltd. All rights reserved.

  16. 26 CFR 1.872-2 - Exclusions from gross income of nonresident alien individuals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... certain exchange or training programs—(1) Exclusion from income. Compensation paid to a nonresident alien... “exchange visitor” under section 201 of the U.S. Information and Educational Exchange Act of 1948 (22 U.S.C. 1446), which section was repealed by section 111 of the Mutual Education and Cultural Exchange Act of...

  17. 26 CFR 1.872-2 - Exclusions from gross income of nonresident alien individuals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... certain exchange or training programs—(1) Exclusion from income. Compensation paid to a nonresident alien... “exchange visitor” under section 201 of the U.S. Information and Educational Exchange Act of 1948 (22 U.S.C. 1446), which section was repealed by section 111 of the Mutual Education and Cultural Exchange Act of...

  18. 26 CFR 1.872-2 - Exclusions from gross income of nonresident alien individuals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... certain exchange or training programs—(1) Exclusion from income. Compensation paid to a nonresident alien... “exchange visitor” under section 201 of the U.S. Information and Educational Exchange Act of 1948 (22 U.S.C. 1446), which section was repealed by section 111 of the Mutual Education and Cultural Exchange Act of...

  19. 47 CFR 73.5000 - Services subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... following broadcast services are subject to competitive bidding: AM; FM; FM translator; analog television; low-power television; television translator; and Class A television. Mutually exclusive applications...

  20. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public interest. (d)-(j) [Reserved] ...

  1. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public interest. (d)-(j) [Reserved] ...

  2. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Services. (b) An application will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public...

  3. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Services. (b) An application will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public...

  4. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public interest. (d)-(j) [Reserved] ...

  5. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Services. (b) An application will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public...

  6. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Services. (b) An application will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public...

  7. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public interest. (d)-(j) [Reserved] ...

  8. 47 CFR 27.321 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Services. (b) An application will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public...

  9. 47 CFR 24.831 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... will be entitled to comparative consideration with one or more conflicting applications only if the Commission determines that such comparative consideration will serve the public interest. (d)-(j) [Reserved] ...

  10. Alternative splicing of mutually exclusive exons--a review.

    PubMed

    Pohl, Martin; Bortfeldt, Ralf H; Grützmann, Konrad; Schuster, Stefan

    2013-10-01

    Alternative splicing (AS) of pre-mRNAs in higher eukaryotes and several viruses is one major source of protein diversity. Usually, the following major subtypes of AS are distinguished: exon skipping, intron retention, and alternative 3' and 5' splice sites. Moreover, mutually exclusive exons (MXEs) represent a rare subtype. In the splicing of MXEs, two (or more) splicing events are not independent anymore, but are executed or disabled in a coordinated manner. In this review, several bioinformatics approaches for analyzing MXEs are presented and discussed. In particular, we revisit suitable definitions and nomenclatures, and bioinformatics tools for finding MXEs, adjacent and non-adjacent MXEs, clustered and grouped MXEs. Moreover, the molecular mechanisms for splicing MXEs proposed in the literature are reviewed and discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. B Cell Antigen Receptor Signaling and Internalization Are Mutually Exclusive Events

    PubMed Central

    Hou, Ping; Araujo, Elizabeth; Zhao, Tong; Zhang, Miao; Massenburg, Don; Veselits, Margaret; Doyle, Colleen; Dinner, Aaron R; Clark, Marcus R

    2006-01-01

    Engagement of the B cell antigen receptor initiates two concurrent processes, signaling and receptor internalization. While both are required for normal humoral immune responses, the relationship between these two processes is unknown. Herein, we demonstrate that following receptor ligation, a small subpopulation of B cell antigen receptors are inductively phosphorylated and selectively retained at the cell surface where they can serve as scaffolds for the assembly of signaling molecules. In contrast, the larger population of non-phosphorylated receptors is rapidly endocytosed. Each receptor can undergo only one of two mutually exclusive fates because the tyrosine-based motifs that mediate signaling when phosphorylated mediate internalization when not phosphorylated. Mathematical modeling indicates that the observed competition between receptor phosphorylation and internalization enhances signaling responses to low avidity ligands. PMID:16719564

  12. The classification of anxiety and hysterical states. Part I. Historical review and empirical delineation.

    PubMed

    Sheehan, D V; Sheehan, K H

    1982-08-01

    The history of the classification of anxiety, hysterical, and hypochondriacal disorders is reviewed. Problems in the ability of current classification schemes to predict, control, and describe the relationship between the symptoms and other phenomena are outlined. Existing classification schemes failed the first test of a good classification model--that of providing categories that are mutually exclusive. The independence of these diagnostic categories from each other does not appear to hold up on empirical testing. In the absence of inherently mutually exclusive categories, further empirical investigation of these classes is obstructed since statistically valid analysis of the nominal data and any useful multivariate analysis would be difficult if not impossible. It is concluded that the existing classifications are unsatisfactory and require some fundamental reconceptualization.

  13. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA licenses subject to competitive bidding. Mutually exclusive applications for initial authorization for the...

  14. Formin and capping protein together embrace the actin filament in a ménage à trois

    PubMed Central

    Shekhar, Shashank; Kerleau, Mikael; Kühn, Sonja; Pernier, Julien; Romet-Lemonne, Guillaume; Jégou, Antoine; Carlier, Marie-France

    2015-01-01

    Proteins targeting actin filament barbed ends play a pivotal role in motile processes. While formins enhance filament assembly, capping protein (CP) blocks polymerization. On their own, they both bind barbed ends with high affinity and very slow dissociation. Their barbed-end binding is thought to be mutually exclusive. CP has recently been shown to be present in filopodia and controls their morphology and dynamics. Here we explore how CP and formins may functionally coregulate filament barbed-end assembly. We show, using kinetic analysis of individual filaments by microfluidics-assisted fluorescence microscopy, that CP and mDia1 formin are able to simultaneously bind barbed ends. This is further confirmed using single-molecule imaging. Their mutually weakened binding enables rapid displacement of one by the other. We show that formin FMNL2 behaves similarly, thus suggesting that this is a general property of formins. Implications in filopodia regulation and barbed-end structural regulation are discussed. PMID:26564775

  15. 47 CFR 22.201 - Paging geographic area authorizations are subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Licensing Requirements and Procedures Competitive.... Mutually exclusive initial applications for paging geographic area licenses are subject to competitive...

  16. Genomic Characterization of Variable Surface Antigens Reveals a Telomere Position Effect as a Prerequisite for RNA Interference-Mediated Silencing in Paramecium tetraurelia

    PubMed Central

    Baranasic, Damir; Oppermann, Timo; Cheaib, Miriam; Cullum, John; Schmidt, Helmut

    2014-01-01

    ABSTRACT Antigenic or phenotypic variation is a widespread phenomenon of expression of variable surface protein coats on eukaryotic microbes. To clarify the mechanism behind mutually exclusive gene expression, we characterized the genetic properties of the surface antigen multigene family in the ciliate Paramecium tetraurelia and the epigenetic factors controlling expression and silencing. Genome analysis indicated that the multigene family consists of intrachromosomal and subtelomeric genes; both classes apparently derive from different gene duplication events: whole-genome and intrachromosomal duplication. Expression analysis provides evidence for telomere position effects, because only subtelomeric genes follow mutually exclusive transcription. Microarray analysis of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to serotype-pure wild-type cultures, shows cotranscription of a subset of subtelomeric genes, indicating that the telomere position effect is due to a selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We present a model of surface antigen evolution by intrachromosomal gene duplication involving the maintenance of positive selection of structurally relevant regions. Further analysis of chromosome heterogeneity shows that alternative telomere addition regions clearly affect transcription of closely related genes. Consequently, chromosome fragmentation appears to be of crucial importance for surface antigen expression and evolution. Our data suggest that RNAi-mediated control of this genetic network by trans-acting RNAs allows rapid epigenetic adaptation by phenotypic variation in combination with long-term genetic adaptation by Darwinian evolution of antigen genes. PMID:25389173

  17. The Generalized Quantum Episodic Memory Model.

    PubMed

    Trueblood, Jennifer S; Hemmer, Pernille

    2017-11-01

    Recent evidence suggests that experienced events are often mapped to too many episodic states, including those that are logically or experimentally incompatible with one another. For example, episodic over-distribution patterns show that the probability of accepting an item under different mutually exclusive conditions violates the disjunction rule. A related example, called subadditivity, occurs when the probability of accepting an item under mutually exclusive and exhaustive instruction conditions sums to a number >1. Both the over-distribution effect and subadditivity have been widely observed in item and source-memory paradigms. These phenomena are difficult to explain using standard memory frameworks, such as signal-detection theory. A dual-trace model called the over-distribution (OD) model (Brainerd & Reyna, 2008) can explain the episodic over-distribution effect, but not subadditivity. Our goal is to develop a model that can explain both effects. In this paper, we propose the Generalized Quantum Episodic Memory (GQEM) model, which extends the Quantum Episodic Memory (QEM) model developed by Brainerd, Wang, and Reyna (2013). We test GQEM by comparing it to the OD model using data from a novel item-memory experiment and a previously published source-memory experiment (Kellen, Singmann, & Klauer, 2014) examining the over-distribution effect. Using the best-fit parameters from the over-distribution experiments, we conclude by showing that the GQEM model can also account for subadditivity. Overall these results add to a growing body of evidence suggesting that quantum probability theory is a valuable tool in modeling recognition memory. Copyright © 2016 Cognitive Science Society, Inc.

  18. 47 CFR 25.155 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... NGSO-like space station license, within the meaning of § 25.157, will be entitled to comparative... GSO-like space station license, within the meaning of § 25.158, will be entitled to comparative...

  19. 47 CFR 25.155 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... NGSO-like space station license, within the meaning of § 25.157, will be entitled to comparative... GSO-like space station license, within the meaning of § 25.158, will be entitled to comparative...

  20. 47 CFR 25.155 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... NGSO-like space station license, within the meaning of § 25.157, will be entitled to comparative... GSO-like space station license, within the meaning of § 25.158, will be entitled to comparative...

  1. 47 CFR 25.155 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... NGSO-like space station license, within the meaning of § 25.157, will be entitled to comparative... GSO-like space station license, within the meaning of § 25.158, will be entitled to comparative...

  2. 47 CFR 25.155 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... NGSO-like space station license, within the meaning of § 25.157, will be entitled to comparative... GSO-like space station license, within the meaning of § 25.158, will be entitled to comparative...

  3. Are Data Sharing and Privacy Protection Mutually Exclusive?

    PubMed

    Joly, Yann; Dyke, Stephanie O M; Knoppers, Bartha M; Pastinen, Tomi

    2016-11-17

    We review emerging strategies to protect the privacy of research participants in international epigenome research: open consent, genome donation, registered access, automated procedures, and privacy-enhancing technologies. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Fractional exclusion and braid statistics in one dimension: a study via dimensional reduction of Chern-Simons theory

    NASA Astrophysics Data System (ADS)

    Ye, Fei; Marchetti, P. A.; Su, Z. B.; Yu, L.

    2017-09-01

    The relation between braid and exclusion statistics is examined in one-dimensional systems, within the framework of Chern-Simons statistical transmutation in gauge invariant form with an appropriate dimensional reduction. If the matter action is anomalous, as for chiral fermions, a relation between braid and exclusion statistics can be established explicitly for both mutual and nonmutual cases. However, if it is not anomalous, the exclusion statistics of emergent low energy excitations is not necessarily connected to the braid statistics of the physical charged fields of the system. Finally, we also discuss the bosonization of one-dimensional anyonic systems through T-duality. Dedicated to the memory of Mario Tonin.

  5. The importance of mutual positive expressivity in social adjustment: understanding the role of peers and gender.

    PubMed

    Sallquist, Julie; DiDonato, Matthew D; Hanish, Laura D; Martin, Carol Lynn; Fabes, Richard A

    2012-04-01

    The relations between young children's mutual (reciprocated) and overall positive emotion (PE) with same- and other-gender peers and their social adjustment were explored. Children's PE and peers' PE were observed across the preschool year during peer interactions (N = 166; 46% girls; M age = 52 months). Results revealed that girls and boys had similar frequencies of overall PE and mutual PE when interacting with same-gender peers, but girls were marginally higher compared with boys in overall and mutual PE when interacting with other-gender peers. Girls and boys did not have greater rates of either type of PE after controlling for gender segregation during same- or other-gender interactions. Using structural equation modeling, children's mutual PE, regardless of their gender, positively predicted indicators of positive adjustment (e.g., prosocial behavior, cooperation) and negatively predicted indicators of negative adjustment (e.g., hyperactivity, disruption, exclusion by peers). Children's overall PE did not predict either type of adjustment. Findings support the importance of mutual PE for children's development. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  6. The Importance of Mutual Positive Expressivity in Social Adjustment: Understanding the Role of Peers and Gender

    PubMed Central

    Sallquist, Julie; DiDonato, Matthew D.; Hanish, Laura D.; Martin, Carol Lynn; Fabes, Richard A.

    2011-01-01

    The relations between young children’s mutual (reciprocated) and overall positive emotion (PE) with same- and other-gender peers and their social adjustment were explored. Children’s PE and peers’ PE were observed across the preschool year during peer interactions (N = 166; 46% girls; M age = 52 months). Results revealed that girls and boys had similar frequencies of overall PE and mutual PE when interacting with same-gender peers, but girls were marginally higher compared to boys in overall and mutual PE when interacting with other-gender peers. Girls and boys did not have greater rates of either type of PE after controlling for gender segregation during same- or other-gender interactions. Using structural equation modeling, children’s mutual PE, regardless of their gender, positively predicted indicators of positive adjustment (e.g., prosocial behavior, cooperation) and negatively predicted indicators of negative adjustment (e.g., hyperactivity, disruption, exclusion by peers). Children’s overall PE did not predict either type of adjustment. Findings support the importance of mutual PE for children’s development. PMID:21859190

  7. Prostate Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... P25–1130). For more information, see the USCS technical notes. † Race categories are not mutually exclusive from ... with caution. For more information, see the USCS technical notes. ¶ Data are compiled from cancer registries that ...

  8. Megatrends: Megahype, Megabad.

    ERIC Educational Resources Information Center

    Goldman, Louis

    1983-01-01

    Criticizes John Naisbitt's bestselling novel, "Megatrends," for reifying constructs (industrial society and information society), treating these entities as mutually exclusive, and endowing them with a life cycle. In addition, claims the novel is marred by faddish jargon and is statistically unreliable. (MLF)

  9. 47 CFR 73.872 - Selection procedure for mutually exclusive LPFM applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... locally at least eight hours of programming per day. For purposes of this criterion, local origination is the production of programming, by the licensee, within ten miles of the coordinates of the proposed...

  10. Space Shuttle communications RF switch matrix

    NASA Technical Reports Server (NTRS)

    Winch, R.

    1979-01-01

    The Shuttle Orbiter communications equipment includes phase modulation (PM) and frequency modulation (FM) channels. The PM section has the capability of routing high levels of energy (175 W) from any one of four transmitters to any one of four antennas, mutually exclusive. The FM channel uses a maximum of 15-W power routed from either of two transmitters to one of two antennas, mutually exclusive. The paper describes the design and the theory of a logic-controlled RF switch matrix devised for the purposes cited. Both PM and FM channels are computer-controlled with manual overrides. The logic interface is realized with CMOS logic for low power consumption and high noise immunity. The interior of the switch matrix is maintained at a pressure of 15 psi (90% nitrogen, 10% helium) by an electron beam-welded encapsulation. The computational results confirm the viability of the RF switch matrix concept.

  11. Yucca aloifolia (Asparagaceae) opts out of an obligate pollination mutualism.

    PubMed

    Rentsch, Jeremy D; Leebens-Mack, Jim

    2014-12-01

    • According to Cope's 'law of the unspecialized' highly dependent species interactions are 'evolutionary dead ends,' prone to extinction because reversion to more generalist interactions is thought to be unlikely. Cases of extreme specialization, such as those seen between obligate mutualists, are cast as evolutionarily inescapable, inevitably leading to extinction rather than diversification of participating species. The pollination mutualism between Yucca plants and yucca moths (Tegeticula and Parategeticula) would seem to be locked into such an obligate mutualism. Yucca aloifolia populations, however, can produce large numbers of fruit lacking moth oviposition scars. Here, we investigate the pollination ecology of Y. aloifolia, in search of the non-moth pollination of a Yucca species.• We perform pollinator exclusion studies on Yucca aloifolia and a sympatric yucca species, Y. filamentosa. We then perform postvisit exclusion treatments, an analysis of dissected fruits, and a fluorescent dye transfer experiment.• As expected, Yucca filamentosa plants set fruit only when inflorescences were exposed to crepuscular and nocturnal pollinating yucca moths. In contrast, good fruit set was observed when pollinators were excluded from Y. aloifolia inflorescences from dusk to dawn, and no fruit set was observed when pollinators were excluded during the day. Follow up experiments indicated that European honeybees (Apis mellifera) were passively yet effectively pollinating Y. aloifolia flowers.• These results indicate that even highly specialized mutualisms may not be entirely obligate interactions or evolutionary dead ends. © 2014 Botanical Society of America, Inc.

  12. The Molecular Basis of TnrA Control by Glutamine Synthetase in Bacillus subtilis*

    PubMed Central

    Hauf, Ksenia; Kayumov, Airat; Gloge, Felix; Forchhammer, Karl

    2016-01-01

    TnrA is a master regulator of nitrogen assimilation in Bacillus subtilis. This study focuses on the mechanism of how glutamine synthetase (GS) inhibits TnrA function in response to key metabolites ATP, AMP, glutamine, and glutamate. We suggest a model of two mutually exclusive GS conformations governing the interaction with TnrA. In the ATP-bound state (A-state), GS is catalytically active but unable to interact with TnrA. This conformation was stabilized by phosphorylated l-methionine sulfoximine (MSX), fixing the enzyme in the transition state. When occupied by glutamine (or its analogue MSX), GS resides in a conformation that has high affinity for TnrA (Q-state). The A- and Q-state are mutually exclusive, and in agreement, ATP and glutamine bind to GS in a competitive manner. At elevated concentrations of glutamine, ATP is no longer able to bind GS and to bring it into the A-state. AMP efficiently competes with ATP and prevents formation of the A-state, thereby favoring GS-TnrA interaction. Surface plasmon resonance analysis shows that TnrA bound to a positively regulated promoter fragment binds GS in the Q-state, whereas it rapidly dissociates from a negatively regulated promoter fragment. These data imply that GS controls TnrA activity at positively controlled promoters by shielding the transcription factor in the DNA-bound state. According to size exclusion and multiangle light scattering analysis, the dodecameric GS can bind three TnrA dimers. The highly interdependent ligand binding properties of GS reveal this enzyme as a sophisticated sensor of the nitrogen and energy state of the cell to control the activity of DNA-bound TnrA. PMID:26635369

  13. An invasive slug exploits an ant-seed dispersal mutualism.

    PubMed

    Meadley Dunphy, Shannon A; Prior, Kirsten M; Frederickson, Megan E

    2016-05-01

    Plant-animal mutualisms, such as seed dispersal, are often vulnerable to disruption by invasive species. Here, we show for the first time how a non-ant invasive species negatively affects seed dispersal by ants. We examined the effects of several animal species that co-occur in a temperate deciduous forest-including native and invasive seed-dispersing ants (Aphaenogaster rudis and Myrmica rubra, respectively), an invasive slug (Arion subfuscus), and native rodents-on a native myrmecochorous plant, Asarum canadense. We experimentally manipulated ant, slug, and rodent access to seed depots and measured seed removal. We also video-recorded depots to determine which other taxa interact with seeds. We found that A. rudis was the main disperser of seeds and that A. subfuscus consumed elaiosomes without dispersing seeds. Rodent visitation was rare, and rodent exclusion had no significant effect on seed or elaiosome removal. We then used data obtained from laboratory and field mesocosm experiments to determine how elaiosome robbing by A. subfuscus affects seed dispersal by A. rudis and M. rubra. We found that elaiosome robbing by slugs reduced seed dispersal by ants, especially in mesocosms with A. rudis, which picks up seeds more slowly than M. rubra. Taken together, our results show that elaiosome robbing by an invasive slug reduces seed dispersal by ants, suggesting that invasive slugs can have profound negative effects on seed dispersal mutualisms.

  14. The identification of Haemonchus species and diagnosis of Haemonchosis

    USDA-ARS?s Scientific Manuscript database

    Diagnosis is often equated with identification or detection when discussing parasitic diseases. Unfortunately, these are not necessarily mutually exclusive activities; diseases and infections are generally diagnosed and organisms are identified. Diagnosis is commonly predicated upon some clinical si...

  15. 47 CFR 73.855 - Ownership limits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES... station shall be granted to any party if the grant of that authorization will result in any such party... face a mutually exclusive challenge. [73 FR 3216, Jan. 17, 2008] ...

  16. Sequential mutations in Notch1, Fbxw7, and Tp53 in radiation-induced mouse thymic lymphomas.

    PubMed

    Jen, Kuang-Yu; Song, Ihn Young; Banta, Karl Luke; Wu, Di; Mao, Jian-Hua; Balmain, Allan

    2012-01-19

    T-cell acute lymphoblastic lymphomas commonly demonstrate activating Notch1 mutations as well as mutations or deletions in Fbxw7. However, because Fbxw7 targets Notch1 for degradation, genetic alterations in these genes are expected to be mutually exclusive events in lymphomagenesis. Previously, by using a radiation-induced Tp53-deficient mouse model for T-cell acute lymphoblastic lymphoma, we reported that loss of heterozygosity at the Fbxw7 locus occurs frequently in a Tp53-dependent manner. In the current study, we show that these thymic lymphomas also commonly exhibit activating Notch1 mutations in the proline-glutamic acid-serine-threonine (PEST) domain. Moreover, concurrent activating Notch1 PEST domain mutations and single-copy deletions at the Fbxw7 locus occur with high frequency in the same individual tumors, indicating that these changes are not mutually exclusive events. We further demonstrate that although Notch1 PEST domain mutations are independent of Tp53 status, they are completely abolished in mice with germline Fbxw7 haploinsufficiency. Therefore, Notch1 PEST domain mutations only occur when Fbxw7 expression levels are intact. These data suggest a temporal sequence of mutational events involving these important cancer-related genes, with Notch1 PEST domain mutations occurring first, followed by Fbxw7 deletion, and eventually by complete loss of Tp53.

  17. EVIDENCE FOR SIMULTANEOUS JETS AND DISK WINDS IN LUMINOUS LOW-MASS X-RAY BINARIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Homan, Jeroen; Neilsen, Joseph; Allen, Jessamyn L.

    Recent work on jets and disk winds in low-mass X-ray binaries (LMXBs) suggests that they are to a large extent mutually exclusive, with jets observed in spectrally hard states and disk winds observed in spectrally soft states. In this paper we use existing literature on jets and disk winds in the luminous neutron star (NS) LMXB GX 13+1, in combination with archival Rossi X-ray Timing Explorer data, to show that this source is likely able to produce jets and disk winds simultaneously. We find that jets and disk winds occur in the same location on the source’s track in itsmore » X-ray color–color diagram. A further study of literature on other luminous LMXBs reveals that this behavior is more common, with indications for simultaneous jets and disk winds in the black hole LMXBs V404 Cyg and GRS 1915+105 and the NS LMXBs Sco X-1 and Cir X-1. For the three sources for which we have the necessary spectral information, we find that simultaneous jets/winds all occur in their spectrally hardest states. Our findings indicate that in LMXBs with luminosities above a few tens of percent of the Eddington luminosity, jets and disk winds are not mutually exclusive, and the presence of disk winds does not necessarily result in jet suppression.« less

  18. Simultaneous Identification of Multiple Driver Pathways in Cancer

    PubMed Central

    Leiserson, Mark D. M.; Blokh, Dima

    2013-01-01

    Distinguishing the somatic mutations responsible for cancer (driver mutations) from random, passenger mutations is a key challenge in cancer genomics. Driver mutations generally target cellular signaling and regulatory pathways consisting of multiple genes. This heterogeneity complicates the identification of driver mutations by their recurrence across samples, as different combinations of mutations in driver pathways are observed in different samples. We introduce the Multi-Dendrix algorithm for the simultaneous identification of multiple driver pathways de novo in somatic mutation data from a cohort of cancer samples. The algorithm relies on two combinatorial properties of mutations in a driver pathway: high coverage and mutual exclusivity. We derive an integer linear program that finds set of mutations exhibiting these properties. We apply Multi-Dendrix to somatic mutations from glioblastoma, breast cancer, and lung cancer samples. Multi-Dendrix identifies sets of mutations in genes that overlap with known pathways – including Rb, p53, PI(3)K, and cell cycle pathways – and also novel sets of mutually exclusive mutations, including mutations in several transcription factors or other genes involved in transcriptional regulation. These sets are discovered directly from mutation data with no prior knowledge of pathways or gene interactions. We show that Multi-Dendrix outperforms other algorithms for identifying combinations of mutations and is also orders of magnitude faster on genome-scale data. Software available at: http://compbio.cs.brown.edu/software. PMID:23717195

  19. Congenital Defects.

    ERIC Educational Resources Information Center

    Goldman, Allen S.; And Others

    There are two general categories (not necessarily mutually exclusive) of congenital defects: (1) abnormalities that have an hereditary basis, such as single and multiple genes, or chromosomal abberration; and (2) abnormalities that are caused by nonhereditary factors, such as malnutrition, maternal disease, radiation, infections, drugs, or…

  20. Taking on Nationalism in the Name of Intercultural Competence

    ERIC Educational Resources Information Center

    Meadows, Bryan

    2010-01-01

    Nationalism presents significant challenges to intercultural competence instruction. On the one hand, nationalism promotes the compartmentalization of communities into mutually-exclusive and discretely-defined nationalist entities. In complementary fashion, nationalism also advocates the homogenization of cultural and linguistic practices within…

  1. Acromyrmex Leaf-Cutting Ants Have Simple Gut Microbiota with Nitrogen-Fixing Potential

    PubMed Central

    Zhukova, Mariya; Hansen, Lars H.; Sørensen, Søren J.; Schiøtt, Morten

    2015-01-01

    Ants and termites have independently evolved obligate fungus-farming mutualisms, but their gardening procedures are fundamentally different, as the termites predigest their plant substrate whereas the ants deposit it directly on the fungus garden. Fungus-growing termites retained diverse gut microbiota, but bacterial gut communities in fungus-growing leaf-cutting ants have not been investigated, so it is unknown whether and how they are specialized on an exclusively fungal diet. Here we characterized the gut bacterial community of Panamanian Acromyrmex species, which are dominated by only four bacterial taxa: Wolbachia, Rhizobiales, and two Entomoplasmatales taxa. We show that the Entomoplasmatales can be both intracellular and extracellular across different gut tissues, Wolbachia is mainly but not exclusively intracellular, and the Rhizobiales species is strictly extracellular and confined to the gut lumen, where it forms biofilms along the hindgut cuticle supported by an adhesive matrix of polysaccharides. Tetracycline diets eliminated the Entomoplasmatales symbionts but hardly affected Wolbachia and only moderately reduced the Rhizobiales, suggesting that the latter are protected by the biofilm matrix. We show that the Rhizobiales symbiont produces bacterial NifH proteins that have been associated with the fixation of nitrogen, suggesting that these compartmentalized hindgut symbionts alleviate nutritional constraints emanating from an exclusive fungus garden diet reared on a substrate of leaves. PMID:26048932

  2. On Reformulating Planning as Dynamic Constraint Satisfaction

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy; Jonsson, Ari K.; Morris, Paul; Koga, Dennis (Technical Monitor)

    2000-01-01

    In recent years, researchers have reformulated STRIPS planning problems as SAT problems or CSPs. In this paper, we discuss the Constraint-Based Interval Planning (CBIP) paradigm, which can represent planning problems incorporating interval time and resources. We describe how to reformulate mutual exclusion constraints for a CBIP-based system, the Extendible Uniform Remote Operations Planner Architecture (EUROPA). We show that reformulations involving dynamic variable domains restrict the algorithms which can be used to solve the resulting DCSP. We present an alternative formulation which does not employ dynamic domains, and describe the relative merits of the different reformulations.

  3. An Aspect of Political Socialization of Student Movement Participants in Korea.

    ERIC Educational Resources Information Center

    Park, Byeong-chul

    1993-01-01

    Tests hypotheses from lineage socialization and generation unit perspectives on Korean student protest participation using 360 self-administered questionnaires collected at 3 Korean universities. Results indicate that these hypotheses are not mutually exclusive but support the generation unit model. (SLD)

  4. Joint hypermobility, growing pain and obesity are mutually exclusive as causes of musculoskeletal pain in schoolchildren.

    PubMed

    Sperotto, Francesca; Balzarin, Marta; Parolin, Mattia; Monteforte, Nadia; Vittadello, Fabio; Zulian, Francesco

    2014-01-01

    Chronic musculoskeletal pain (MSP) is common in children and can be due to several non-inflammatory conditions such as the benign joint hypermobility syndrome (BJHS), and growing pains (GP). We evaluated frequency, risk factors and causes of MSP in a large cohort of healthy schoolchildren. We conducted a cross sectional study in a cohort of healthy schoolchildren, aged 8-13 years, by collecting information and performing a physical examination. The anamnesis was focused on family history for MSP, presence and sites of MSP interfering with the regular daily activities during the previous 6 months and presence of GP. Physical examination included body mass index, pubertal stage and musculoskeletal examination focused on the presence of hypermobility according to the Beighton criteria. Two hundred and eighty-nine schoolchildren, 143 females and 146 males, participated in the study. Chronic MSP occurred in 30.4% of subjects, BJHS occurred in 13.2%. GJH was more frequent in symptomatic subjects than in asymptomatic ones (p=0.054). Symptomatic subjects were more frequently pre-pubertal than pubertal (p=0.006). In general, GP, BJHS and obesity (OB) were mutually exclusive as causes of MSP as, among 88 symptomatic subjects, 52.3% had GP, 40.9% presented BJHS, 4.5% were OB and only two (2.3%) presented both BJHS and OB. After puberty, GP persisted in 66.7%, BJHS in 26.7% and in association with OB in 6.7%. Approximately one third of schoolchildren suffer from MSP. BJHS, GP and OB are mutually exclusive as causes of MSP in schoolchildren. Pubertal stage plays an important role in the physiopathology of this condition.

  5. EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.

    PubMed

    Petrini, Iacopo; Lencioni, Monica; Vasile, Enrico; Fornaro, Lorenzo; Belluomini, Lorenzo; Pasquini, Giulia; Ginocchi, Laura; Caparello, Chiara; Musettini, Gianna; Vivaldi, Caterina; Caponi, Sara; Ricci, Sergio; Proietti, Agenese; Fontanini, Gabriella; Naccarato, Antonio Giuseppe; Nardini, Vincenzo; Santi, Stefano; Falcone, Alfredo

    2018-02-14

    The evaluation of molecular targets in gastric cancer has demonstrated the predictive role of HER2 amplification for trastuzumab treatment in metastatic gastric cancer. Besides HER2, other molecular targets are under evaluation in metastatic gastric tumors. However, very little is known about their role in resected tumors. We evaluated the expression of HER2, EGFR, MET, AKT1 and phospho-mTOR in resected stage II-III adenocarcinomas. Ninety-two patients with resected stomach (63%) or gastro-esophageal adenocarcinomas (27%) were evaluated. Antibodies anti-HER2, EGFR, MET, AKT1 and phospho-mTOR were used for immunostaining of formalin-fixed paraffin-embedded slides. Using FISH, HER2 amplification was evaluated in cases with an intermediate (+2) staining. EGFR overexpression (11%) was a poor prognostic factor for overall survival (3-year OS: 47% vs 77%; Log-Rank p= 0.033). MET overexpression (36%) was associated with a trend for a worse survival (3-year OS: 65% vs 77%; Log-Rank p= 0.084). HER2 amplification/overexpression and mTOR hyper-phosphorylation were observed in 13% and 48% of tumors, respectively. AKT1 overexpression (8%) was not a prognostic factor by itself (p= 0.234). AKT1 and EGFR overexpression was mutually exclusive and patients with EGFR or AKT1 overexpression experienced a poor prognosis (3-year OS: 52% vs. 79%, Log-Rank p= 0.005). EGFR is confirmed a poor prognostic factor in resected gastric cancers. We firstly describe a mutually exclusive overexpression of EGFR and AKT1 with potential prognostic implications, suggesting the relevance of this pathway for the growth of gastric cancers.

  6. Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework

    PubMed Central

    Eldridge, Sandra M.; Lancaster, Gillian A.; Campbell, Michael J.; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L.; Bond, Christine M.

    2016-01-01

    We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms ‘pilot’ and ‘feasibility’ in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms ‘feasibility’ or ‘pilot’ as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term ‘feasibility’ in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention. PMID:26978655

  7. Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

    PubMed

    Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M

    2016-01-01

    We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

  8. Were Workers of Eusocial Hymenoptera Initially Altruistic or Oppressed?*

    PubMed Central

    Michener, Charles D.; Brothers, Denis J.

    1974-01-01

    Studies of a primitively eusocial halictid bee, Lasioglossum zephyrum, strongly suggest that a major factor in originating a worker caste is selection at the individual level for queens that control associated adult females. Even in this scarcely social form, the queen inhibits other adult females from becoming queens, perhaps by her high level of activity and frequent nudging in the nest. Queens are behaviorally less varied than workers and show specialization, particularly in frequency of nudging (which is concentrated on the worker with largest ovaries) and of backing. Backing draws workers, especially those with slender ovaries, down to lower parts of the burrows where the stimuli for cell construction and provisioning probably operate. Eating of worker-laid eggs by queens was also noted. In spite of the suggestion that queens have evolved to control their workers rather than that workers have evolved to help their queens, both may well have occurred, for these processes are not mutually exclusive; moreover, social attributes mutually beneficial to both castes no doubt have arisen. PMID:16592144

  9. Antagonistic Self-Organizing Patterning Systems Control Maintenance and Regeneration of the Anteroposterior Axis in Planarians.

    PubMed

    Stückemann, Tom; Cleland, James Patrick; Werner, Steffen; Thi-Kim Vu, Hanh; Bayersdorf, Robert; Liu, Shang-Yun; Friedrich, Benjamin; Jülicher, Frank; Rink, Jochen Christian

    2017-02-06

    Planarian flatworms maintain their body plan in the face of constant internal turnover and can regenerate from arbitrary tissue fragments. Both phenomena require self-maintaining and self-organizing patterning mechanisms, the molecular mechanisms of which remain poorly understood. We show that a morphogenic gradient of canonical Wnt signaling patterns gene expression along the planarian anteroposterior (A/P) axis. Our results demonstrate that gradient formation likely occurs autonomously in the tail and that an autoregulatory module of Wnt-mediated Wnt expression both shapes the gradient at steady state and governs its re-establishment during regeneration. Functional antagonism between the tail Wnt gradient and an unknown head patterning system further determines the spatial proportions of the planarian A/P axis and mediates mutually exclusive molecular fate choices during regeneration. Overall, our results suggest that the planarian A/P axis is patterned by self-organizing patterning systems deployed from either end that are functionally coupled by mutual antagonism. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 47 CFR 80.1251 - Maritime communications subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime communications subject to competitive... AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Competitive Bidding Procedures § 80.1251 Maritime communications subject to competitive bidding. Mutually exclusive initial applications for VPCSA...

  11. 47 CFR 1.227 - Consolidations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... under part 101, subparts H and O, Private Operational Fixed Microwave Service, and applications for high... application or applications are received by the Commission's offices in Gettysburg, PA (or St. Louis, Missouri... Microwave Service, mutual exclusivity will occur if two or more acceptable applications that are in conflict...

  12. Finding Common Ground

    ERIC Educational Resources Information Center

    Benson, Jeffrey

    2017-01-01

    Regular education teachers and special educators shouldn't view their jobs as mutually exclusive, writes Jeffrey Benson in this article. He argues that all students benefit when both teachers form collaborative partnerships. Drawing on his four decades of experience in schools, Benson details how regular education teachers can incorporate ideas…

  13. NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component.

    PubMed

    Shi, Hexin; Wang, Ying; Li, Xiaohong; Zhan, Xiaoming; Tang, Miao; Fina, Maggy; Su, Lijing; Pratt, David; Bu, Chun Hui; Hildebrand, Sara; Lyon, Stephen; Scott, Lindsay; Quan, Jiexia; Sun, Qihua; Russell, Jamie; Arnett, Stephanie; Jurek, Peter; Chen, Ding; Kravchenko, Vladimir V; Mathison, John C; Moresco, Eva Marie Y; Monson, Nancy L; Ulevitch, Richard J; Beutler, Bruce

    2016-03-01

    The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1β (IL-1β) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.

  14. Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum.

    PubMed Central

    Scherf, A; Hernandez-Rivas, R; Buffet, P; Bottius, E; Benatar, C; Pouvelle, B; Gysin, J; Lanzer, M

    1998-01-01

    Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P.falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs in situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. In situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation. PMID:9736619

  15. Adaptive color halftoning for minimum perceived error using the blue noise mask

    NASA Astrophysics Data System (ADS)

    Yu, Qing; Parker, Kevin J.

    1997-04-01

    Color halftoning using a conventional screen requires careful selection of screen angles to avoid Moire patterns. An obvious advantage of halftoning using a blue noise mask (BNM) is that there are no conventional screen angle or Moire patterns produced. However, a simple strategy of employing the same BNM on all color planes is unacceptable in case where a small registration error can cause objectionable color shifts. In a previous paper by Yao and Parker, strategies were presented for shifting or inverting the BNM as well as using mutually exclusive BNMs for different color planes. In this paper, the above schemes will be studied in CIE-LAB color space in terms of root mean square error and variance for luminance channel and chrominance channel respectively. We will demonstrate that the dot-on-dot scheme results in minimum chrominance error, but maximum luminance error and the 4-mask scheme results in minimum luminance error but maximum chrominance error, while the shift scheme falls in between. Based on this study, we proposed a new adaptive color halftoning algorithm that takes colorimetric color reproduction into account by applying 2-mutually exclusive BNMs on two different color planes and applying an adaptive scheme on other planes to reduce color error. We will show that by having one adaptive color channel, we obtain increased flexibility to manipulate the output so as to reduce colorimetric error while permitting customization to specific printing hardware.

  16. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and in the 24 GHz Service, will be entitled to comparative consideration with one or more conflicting... comparative consideration with one or more conflicting applications in accordance with the provisions of § 1...), except under any of the following circumstances: (1) The application has been designated for comparative...

  17. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and in the 24 GHz Service, will be entitled to comparative consideration with one or more conflicting... comparative consideration with one or more conflicting applications in accordance with the provisions of § 1...), except under any of the following circumstances: (1) The application has been designated for comparative...

  18. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... and in the 24 GHz Service, will be entitled to comparative consideration with one or more conflicting... comparative consideration with one or more conflicting applications in accordance with the provisions of § 1...), except under any of the following circumstances: (1) The application has been designated for comparative...

  19. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and in the 24 GHz Service, will be entitled to comparative consideration with one or more conflicting... comparative consideration with one or more conflicting applications in accordance with the provisions of § 1...), except under any of the following circumstances: (1) The application has been designated for comparative...

  20. 47 CFR 101.45 - Mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and in the 24 GHz Service, will be entitled to comparative consideration with one or more conflicting... comparative consideration with one or more conflicting applications in accordance with the provisions of § 1...), except under any of the following circumstances: (1) The application has been designated for comparative...

  1. 47 CFR 73.7004 - Petitions to deny tentative selectee(s).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Educational Channels, and for Certain Applications for Noncommercial Educational Stations on Non-Reserved Channels § 73.7004 Petitions to deny tentative selectee(s). (a) For mutually exclusive applicants subject... announcing the tentative selection of an applicant through fair distribution (§ 73.7002) or point system...

  2. Knowledge and Power in Higher Education: A Reader.

    ERIC Educational Resources Information Center

    Brown, Richard Harvey, Ed.; Schubert, J. Daniel, Ed.

    This collection of essays is authored by social scientists who are concerned primarily with relationships between academic knowledge and political power, rethinking the traditional view of politics and science as mutually exclusive fields of study. Chapters are organized into three parts: "Introduction"; "The Institutional Politics of Knowledge…

  3. 76 FR 42573 - Radio Broadcasting Services; Oklahoma and Texas

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-19

    ...: Final rule; application for review. SUMMARY: This document denies the Application for Review filed by... Texas Licenses, L.P. (``Joint Petitioners'') of the dismissal of a second alternative proposal to their...). In response to the NPRM, the Joint Petitioners filed a mutually exclusive Counterproposal involving...

  4. Constraint-based Attribute and Interval Planning

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari; Frank, Jeremy

    2013-01-01

    In this paper we describe Constraint-based Attribute and Interval Planning (CAIP), a paradigm for representing and reasoning about plans. The paradigm enables the description of planning domains with time, resources, concurrent activities, mutual exclusions among sets of activities, disjunctive preconditions and conditional effects. We provide a theoretical foundation for the paradigm, based on temporal intervals and attributes. We then show how the plans are naturally expressed by networks of constraints, and show that the process of planning maps directly to dynamic constraint reasoning. In addition, we de ne compatibilities, a compact mechanism for describing planning domains. We describe how this framework can incorporate the use of constraint reasoning technology to improve planning. Finally, we describe EUROPA, an implementation of the CAIP framework.

  5. 78 FR 71535 - Guidance for Tax-Exempt Social Welfare Organizations on Candidate-Related Political Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... promotes social welfare. Whether such an activity promotes social welfare is an independent determination... mutually exclusive. For example, the category of express advocacy communications may overlap with the... Commission under the Federal Election Campaign Act as an independent expenditure. [[Page 71539

  6. Encouraging Autonomy and Preparing for IELTS: Mutually Exclusive Goals?

    ERIC Educational Resources Information Center

    Barrett-Lennard, Siri

    1997-01-01

    Suggests foreign students in Australia may not be getting preparation needed to integrate successfully into university study. Research is reviewed that indicates these students not only need help preparing for the International English Language Testing System (IELTS) but also with learning at an Australian university. Academic preparation courses…

  7. Race Treatment and Cardiovascular Health: A Study of Men With Prostate Cancer

    DTIC Science & Technology

    2012-10-01

    the cases; paper records were requested on an as-needed basis to supplement electronically available data (only 22 (1.1%) charts were requested for...1.2%) Prostatectomy 102 (10.2%) 115 (11.5%) Alternative/ Herbal Therapy 7 (0.7%) 15 (1.5%) * Not Necessarily Mutually Exclusive Preliminary

  8. Prosecution to Enhance Treatment.

    ERIC Educational Resources Information Center

    Goldsmith, Stephen

    1990-01-01

    Advocates the use of criminal prosecution of pregnant women who abuse illegal substances. Discusses the views that use of drugs is a form of illness and that pregnant women should be exempt from laws. Concludes that court supervision and sanctions can improve treatment. Argues that punishment and treatment need not be mutually exclusive and…

  9. Economic growth, ecological economics, and wilderness preservation

    Treesearch

    Brian Czech

    2000-01-01

    Economic growth is a perennial national goal. Perpetual economic growth and wilderness preservation are mutually exclusive. Wilderness scholarship has not addressed this conflict. The economics profession is unlikely to contribute to resolution, because the neoclassical paradigm holds that there is no limit to economic growth. A corollary of the paradigm is that...

  10. It All Adds Up: Learning Early Math through Play and Games

    ERIC Educational Resources Information Center

    Ramani, Geetha B.; Eason, Sarah H.

    2015-01-01

    Playing and learning mathematics do not have to be mutually exclusive activities, especially in kindergarten. Play and games can give young children opportunities to learn and develop foundational math skills that are aligned with Common Core standards for mathematics through age-appropriate, fun, and engaging activities.

  11. Reconceptualizing Children's Suggestibility: Bidirectional and Temporal Properties

    ERIC Educational Resources Information Center

    Gilstrap, Livia L.; Ceci, Stephen J.

    2005-01-01

    Forty-one children (3 to 7 years) were exposed to a staged event and later interviewed by 1 of 41 professional interviewers. All interviews were coded with a detailed, mutually exclusive, and exhaustive coding scheme capturing adult behaviors (leading questions vs. neutral) and child behaviors (acquiescence vs. denial) in a temporally organized…

  12. 47 CFR 1.227 - Consolidations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...(a), (b), and (d), and § 80.374 of this chapter) mutual exclusivity will occur if the later... and Issues § 1.227 Consolidations. (a) The Commission, upon motion or upon its own motion, will, where... issues, or (2) Any applications which present conflicting claims, except where a random selection process...

  13. 47 CFR 1.227 - Consolidations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...(a), (b), and (d), and § 80.374 of this chapter) mutual exclusivity will occur if the later... and Issues § 1.227 Consolidations. (a) The Commission, upon motion or upon its own motion, will, where... issues, or (2) Any applications which present conflicting claims, except where a random selection process...

  14. 47 CFR 1.227 - Consolidations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...(a), (b), and (d), and § 80.374 of this chapter) mutual exclusivity will occur if the later... and Issues § 1.227 Consolidations. (a) The Commission, upon motion or upon its own motion, will, where... issues, or (2) Any applications which present conflicting claims, except where a random selection process...

  15. Mission-Driven and For-Profit: Not Mutually Exclusive

    ERIC Educational Resources Information Center

    Moritz, Benjamin

    2014-01-01

    In order to counteract some serious misconceptions in Gary Bell's essay "Honors for Sale," Benjamin Moritz opens this essay with inspirational stories of students who overcame disadvantages to complete their college education The first and most fundamental problem the author notes in Bell's essay is the assumption that privatization and…

  16. Conceptual Questions and Lack of Formal Reasoning: Are They Mutually Exclusive?

    ERIC Educational Resources Information Center

    Igaz, Csaba; Proksa, Miroslav

    2012-01-01

    Using specially designed conceptual question pairs, 9th grade students were tested on tasks (presented as experimental situations in pictorial form) that involved controlling the variables' scheme of formal reasoning. The question topics focused on these three chemical contexts: chemistry in everyday life, chemistry without formal concepts, and…

  17. A Comparison of Two-Group Classification Methods

    ERIC Educational Resources Information Center

    Holden, Jocelyn E.; Finch, W. Holmes; Kelley, Ken

    2011-01-01

    The statistical classification of "N" individuals into "G" mutually exclusive groups when the actual group membership is unknown is common in the social and behavioral sciences. The results of such classification methods often have important consequences. Among the most common methods of statistical classification are linear discriminant analysis,…

  18. 47 CFR 90.165 - Procedures for mutually exclusive applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... grant, pursuant to § 1.935 of this chapter. (1) Selection methods. In selecting the application to grant, the Commission may use competitive bidding, random selection, or comparative hearings, depending on... chapter, either before or after employing selection procedures. (3) Type of filing group used. Except as...

  19. 47 CFR 73.3521 - Mutually exclusive applications for low power television, television translators and television...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... television, television translators and television booster stations. 73.3521 Section 73.3521 Telecommunication..., television translators and television booster stations. When there is a pending application for a new low power television, television translator, or television booster station, or for major changes in an...

  20. 47 CFR 73.3521 - Mutually exclusive applications for low power television, television translators and television...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... television, television translators and television booster stations. 73.3521 Section 73.3521 Telecommunication..., television translators and television booster stations. When there is a pending application for a new low power television, television translator, or television booster station, or for major changes in an...

  1. 47 CFR 73.3521 - Mutually exclusive applications for low power television, television translators and television...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... television, television translators and television booster stations. 73.3521 Section 73.3521 Telecommunication..., television translators and television booster stations. When there is a pending application for a new low power television, television translator, or television booster station, or for major changes in an...

  2. 47 CFR 73.3521 - Mutually exclusive applications for low power television, television translators and television...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... television, television translators and television booster stations. 73.3521 Section 73.3521 Telecommunication..., television translators and television booster stations. When there is a pending application for a new low power television, television translator, or television booster station, or for major changes in an...

  3. 47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Competitive Bidding Procedures for 800 MHz Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

  4. 47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Competitive Bidding Procedures for 900 MHz Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 900 MHz SMR service licenses are subject to competitive bidding. The...

  5. Social Network Positions and Smoking Experimentation among Chinese Adolescents

    ERIC Educational Resources Information Center

    Fang, Xiaoyi; Li, Xiaoming; Stanton, Bonita; Dong, Qi

    2003-01-01

    Objective: To explore the relationship between peer social network positions and smoking experimentation among Chinese adolescents. Methods: Self-administered questionnaires were administered to 1040 adolescents in grades 6, 8, and 10. Paired-friendship linkages were used to assign participants into 3 mutually exclusive social network positions.…

  6. 42 CFR 412.620 - Patient classification system.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... weighting factors to reflect changes in— (1) Treatment patterns; (2) Technology; (3) Number of discharges... 42 Public Health 2 2013-10-01 2013-10-01 false Patient classification system. 412.620 Section 412... rehabilitation facilities into mutually exclusive case-mix groups. (2) For purposes of this subpart, case-mix...

  7. 42 CFR 412.620 - Patient classification system.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... weighting factors to reflect changes in— (1) Treatment patterns; (2) Technology; (3) Number of discharges... 42 Public Health 2 2012-10-01 2012-10-01 false Patient classification system. 412.620 Section 412... rehabilitation facilities into mutually exclusive case-mix groups. (2) For purposes of this subpart, case-mix...

  8. 42 CFR 412.620 - Patient classification system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... weighting factors to reflect changes in— (1) Treatment patterns; (2) Technology; (3) Number of discharges... 42 Public Health 2 2014-10-01 2014-10-01 false Patient classification system. 412.620 Section 412... rehabilitation facilities into mutually exclusive case-mix groups. (2) For purposes of this subpart, case-mix...

  9. Studies in Family Planning, Number 52.

    ERIC Educational Resources Information Center

    Population Council, New York, NY.

    The first of the two articles reviews the types of population education currently available, indicating that sex education, education for family living, population awareness, and education for basic value orientations are not mutually exclusive. The objectives and evaluation of such courses are not necessarily identical in different parts of the…

  10. Teaching Geosciences in Mississippi

    ERIC Educational Resources Information Center

    Dewey, Christopher; Beasley, Rodney W.

    2007-01-01

    Historically, two paths have developed in an individual and communal search for understanding and meaning: The study of science and the search for a higher spirituality. Although they should not necessarily be mutually exclusive, the history of science is littered with the collision of these two pathways, for rarely have they met without…

  11. Second Label Learning in Bilingual and Monolingual Infants

    ERIC Educational Resources Information Center

    Kandhadai, Padmapriya; Hall, D. Geoffrey; Werker, Janet F.

    2017-01-01

    "Mutual exclusivity" is the assumption that each object has only one category label. Prior research suggests that bilingual infants, unlike monolingual infants, fail to adhere to this assumption to guide word learning. Yet previous work has not addressed whether bilingual infants systematically interpret a novel word for a familiar…

  12. Putting time into proof outlines

    NASA Technical Reports Server (NTRS)

    Schneider, Fred B.; Bloom, Bard; Marzullo, Keith

    1991-01-01

    A logic for reasoning about timing of concurrent programs is presented. The logic is based on proof outlines and can handle maximal parallelism as well as resource-constrained execution environments. The correctness proof for a mutual exclusion protocol that uses execution timings in a subtle way illustrates the logic in action.

  13. Team Training for Command and Control Systems. Volume II. Recommendations for Research Program.

    DTIC Science & Technology

    1982-04-01

    between individual and group goals and how they are set, the roles of hedonistic individual orientation and altruistic commitment to a group, and... boredom . They are not intended to be definitive, comprehensive, nor exhaustive. They are also not mutually exclusive and other partitionings of the

  14. The Dynamics of Metaphors: Class-Inclusion or Comparison?

    ERIC Educational Resources Information Center

    Drunkenmölle, Tomas

    2012-01-01

    In current literature, metaphor is treated as either an instance of implicit comparison or as a nonliteral class-inclusion statement. I will argue that, contrary to these positions, the notions of comparison and class-inclusion are not mutually exclusive in character but rather complementary cognitive concepts which entail one another. While…

  15. Race Socialization Messages across Historical Time

    ERIC Educational Resources Information Center

    Brown, Tony N.; Lesane-Brown, Chase L.

    2006-01-01

    In this study we investigated whether the content of race socialization messages varied by birth cohort, using data from a national probability sample. Most respondents recalled receiving messages about what it means to be black from their parents or guardians; these messages were coded into five mutually exclusive content categories: individual…

  16. 47 CFR 73.3521 - Mutually exclusive applications for low power television, television translators and television...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... television, television translators and television booster stations. 73.3521 Section 73.3521 Telecommunication..., television translators and television booster stations. When there is a pending application for a new low power television, television translator, or television booster station, or for major changes in an...

  17. Ants farm subterranean aphids mostly in single clone groups - an example of prudent husbandry for carbohydrates and proteins?

    PubMed Central

    2012-01-01

    Background Mutualistic interactions are wide-spread but the mechanisms underlying their evolutionary stability and ecological dynamics remain poorly understood. Cultivation mutualisms in which hosts consume symbionts occur in phylogenetically diverse groups, but often have symbiont monocultures for each host. This is consistent with the prediction that symbionts should avoid coexistence with other strains so that host services continue to benefit relatives, but it is less clear whether hosts should always favor monocultures and what mechanisms they might have to manipulate symbiont diversity. Few mutualisms have been studied in sufficient genetic detail to address these issues, so we decided to characterize symbiont diversity in the complex mutualism between multiple root aphid species and Lasius flavus ants. After showing elsewhere that three of these aphid species have low dispersal and mostly if not exclusively asexual reproduction, we here investigate aphid diversity within and between ant nest mounds. Results The three focal species (Geoica utricularia, Forda marginata and Tetraneura ulmi) had considerable clonal diversity at the population level. Yet more than half of the ant mounds contained just a single aphid species, a significantly higher percentage than expected from a random distribution. Over 60% of these single-species mounds had a single aphid clone, and clones tended to persist across subsequent years. Whenever multiple species/clones co-occurred in the same mound, they were spatially separated with more than 95% of the aphid chambers containing individuals of a single clone. Conclusions L. flavus “husbandry” is characterized by low aphid “livestock” diversity per colony, especially at the nest-chamber level, but it lacks the exclusive monocultures known from other cultivation mutualisms. The ants appear to eat most of the early instar aphids, so that adult aphids are unlikely to face limited phloem resources and scramble competition with other aphids. We suggest that such culling of carbohydrate-providing symbionts for protein ingestion may maintain maximal host yield per aphid while also benefitting the domesticated aphids as long as their clone-mates reproduce successfully. The cost-benefit logic of this type of polyculture husbandry has striking analogies with human farming practices based on slaughtering young animals for meat to maximize milk-production by a carefully regulated adult livestock population. PMID:22747564

  18. Two spatial memories are not better than one: evidence of exclusivity in memory for object location.

    PubMed

    Baguley, Thom; Lansdale, Mark W; Lines, Lorna K; Parkin, Jennifer K

    2006-05-01

    This paper studies the dynamics of attempting to access two spatial memories simultaneously and its implications for the accuracy of recall. Experiment 1 demonstrates in a range of conditions that two cues pointing to different experiences of the same object location produce little or no higher recall than that observed with a single cue. Experiment 2 confirms this finding in a within-subject design where both cues have previously elicited recall. Experiment 3 shows that these findings are only consistent with a model in which two representations of the same object location are mutually exclusive at both encoding and retrieval, and inconsistent with models that assume information from both representations is available. We propose that these representations quantify directionally specific judgments of location relative to specific anchor points in the stimulus; a format that precludes the parallel processing of like representations. Finally, we consider the apparent paradox of how such representations might contribute to the acquisition of spatial knowledge from multiple experiences of the same stimuli.

  19. Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

    PubMed Central

    Oh, Wonjung; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

    2013-01-01

    Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N=392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend’s withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class. PMID:18193479

  20. Trajectories of social withdrawal from middle childhood to early adolescence.

    PubMed

    Oh, Wonjung; Rubin, Kenneth H; Bowker, Julie C; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

    2008-05-01

    Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.

  1. Bet hedging based cooperation can limit kin selection and form a basis for mutualism.

    PubMed

    Uitdehaag, Joost C M

    2011-07-07

    Mutualism is a mechanism of cooperation in which partners that differ help each other. As such, mutualism opposes mechanisms of kin selection and tag-based selection (for example the green beard mechanism), which are based on giving exclusive help to partners that are related or carry the same tag. In contrast to kin selection, which is a basis for parochialism and intergroup warfare, mutualism can therefore be regarded as a mechanism that drives peaceful coexistence between different groups and individuals. Here the competition between mutualism and kin (tag) selection is studied. In a model where kin selection and tag-based selection are dominant, mutualism is promoted by introducing environmental fluctuations. These fluctuations cause reduction in reproductive success by the mechanism of variance discount. The best strategy to counter variance discount is to share with agents who experience the most anticorrelated fluctuations, a strategy called bet hedging. In this way, bet hedging stimulates cooperation with the most unrelated partners, which is a basis for mutualism. Analytic results and simulations reveal that, if this effect is large enough, mutualistic strategies can dominate kin selective strategies. In addition, mutants of these mutualistic strategies that experience fluctuations that are more anticorrelated to their partner, can outcompete wild type, which can lead to the evolution of specialization. In this way, the evolutionary success of mutualistic strategies can be explained by bet hedging-based cooperation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Emerging Trends of Research on Transfer of Learning

    ERIC Educational Resources Information Center

    Subedi, Bhawani Shankar

    2004-01-01

    The terms "transfer of learning" and "transfer of training" are usually found mutually exclusive in training and development literature. Transfer is a key concept in adult learning theories because most education and training aspires to transfer. The end goals of training and education are not achieved unless transfer occurs. Emerging trends of…

  3. Memory Reconsolidation and Extinction in the Crab: Mutual Exclusion or Coexistence?

    ERIC Educational Resources Information Center

    Perez-Cuesta, Luis Maria; Maldonado, Hector

    2009-01-01

    A conditioned stimulus (CS) exposure has the ability to induce two qualitatively different mnesic processes: memory reconsolidation and memory extinction. Previous work from our laboratory has shown that upon a single CS presentation the triggering of one or the other process depends on CS duration (short CS exposure triggers reconsolidation,…

  4. 43 CFR 11.84 - Damage determination phase-implementation guidance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... should determine the uses made of the resource services identified in the Quantification phase. (2) Only committed uses, as that phrase is used in this part, of the resource or services over the recovery period... resource services have mutually exclusive uses, the highest-and-best use of the injured resource or...

  5. Bayesian Network Meta-Analysis for Unordered Categorical Outcomes with Incomplete Data

    ERIC Educational Resources Information Center

    Schmid, Christopher H.; Trikalinos, Thomas A.; Olkin, Ingram

    2014-01-01

    We develop a Bayesian multinomial network meta-analysis model for unordered (nominal) categorical outcomes that allows for partially observed data in which exact event counts may not be known for each category. This model properly accounts for correlations of counts in mutually exclusive categories and enables proper comparison and ranking of…

  6. From Comprehensive to Singular: A Latent Class Analysis of College Teaching Practices

    ERIC Educational Resources Information Center

    Campbell, Corbin M.; Cabrera, Alberto F.; Ostrow Michel, Jessica; Patel, Shikha

    2017-01-01

    While decades of research on college teaching has investigated several forms of classroom practices, much of this research approaches teaching as falling into mutually exclusive paradigms (e.g., active learning vs. lecturing). This paper enters inside the college classroom using external raters to understand patterns of pedagogical practices…

  7. Social Justice and Educational Administration: Mutually Exclusive?

    ERIC Educational Resources Information Center

    Karpinski, Carol F.; Lugg, Catherine A.

    2006-01-01

    Purpose: The purpose of this article is to explore some of the current tensions within educational administration in the USA and conclude with a few cautions for educators who engage in social justice projects. Design/methodology/approach: Using a selective case, this historical essay examines the issues of social justice and equity as they have…

  8. Brain-Immune Interactions as the Basis of Gulf War Illness: Consortium Development

    DTIC Science & Technology

    2012-12-01

    advancements regarding the role of glia in chronic pain processing (Watkins et al., 2007; Watkins et al., 2009), axonal transport deficits in...cytokine signaling) Behavioral Effects (fatigue, pain , cognitive problems) Astrocyte Activation (cytokine signaling) mutually exclusive and once...K. Sullivan, Ph.D. 12 characterized by persistent pain , cognitive dysfunction, and fatigue

  9. Ethnicizing Poverty through Social Security Provision in Rural Hungary

    ERIC Educational Resources Information Center

    Schwarcz, Gyongyi

    2012-01-01

    Rural poverty has become an increasingly ethnicised category for the majority society in contemporary Hungary. The article aims to explore the process and practice of social exclusion and ethnicisation in relation to mutual effects of post-socialist welfare restructuring and changing discourse on poverty in the post-socialist rural reality. The…

  10. Creating Opportunity for All: Building Pathways from Continuing Education to Credit Programs

    ERIC Educational Resources Information Center

    Price, Derek V.; Sedlak, Wendy

    2018-01-01

    Community college students start college with goals including transferring to earn a bachelor's degree and gaining the skills and credentials that have immediate labor market value. These goals are not mutually exclusive. Students deserve access to clear pathways, whether they enroll in short-term education and training programs or in college…

  11. The importance of wilderness to whitebark pine research and management

    Treesearch

    Robert E. Keane

    2000-01-01

    Whitebark pine is a keystone species in upper subalpine forests of the northern Rocky Mountains, Cascades, and Sierra Nevada that has been declining because of recent mountain pine beetle and exotic blister rust epidemics, coupled with advancing succession resulting from fire exclusion. Whitebark pine and Wilderness have a mutually beneficial relationship because 1)...

  12. Does the Association with Psychosomatic Health Problems Differ between Cyberbullying and Traditional Bullying?

    ERIC Educational Resources Information Center

    Beckman, Linda; Hagquist, Curt; Hellstrom, Lisa

    2012-01-01

    The association between mental health problems and traditional bullying is well known, whereas the strength of the association in cyberbullying is less known. This study aimed to compare the association between mutually exclusive groups of bullying involvement and psychosomatic problems as measured by the PsychoSomatic Problems scale. The sample…

  13. Phonological Similarity and Mutual Exclusivity: On-Line Recognition of Atypical Pronunciations in 3-5-Year-Olds

    ERIC Educational Resources Information Center

    Creel, Sarah C.

    2012-01-01

    Recent research has considered the phonological specificity of children's word representations, but few studies have examined the flexibility of those representations. Tolerating acoustic-phonetic deviations has been viewed as a negative in terms of discriminating minimally different word forms, but may be a positive in an increasingly…

  14. 47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false 800 MHz SMR spectrum subject to competitive... Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

  15. 47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false 800 MHz SMR spectrum subject to competitive... Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

  16. 47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false 800 MHz SMR spectrum subject to competitive... Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

  17. 47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false 800 MHz SMR spectrum subject to competitive... Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

  18. The Canvas Mirror: Painting as Politics in the New Deal.

    ERIC Educational Resources Information Center

    Fogel, Jared A.; Stevens, Robert L.

    2001-01-01

    Explores four artistic classifications prominent in depression-era art examining and contrasting examples of each: (1) Regionalism; (2) Social Realism; (3) American Idealism; and (4) Anti-Fascism. Focuses on artworks by the artist Seymour Fogel because his work demonstrates that Regionalism and Social Realism were not mutually exclusive and that…

  19. How to Address the Volitional Dimension of the Engineer's Social Responsibility

    ERIC Educational Resources Information Center

    Heikkero, T.

    2008-01-01

    In this paper I argue that volitional aspects, i.e. ethos, attitude, pathos, will, underlying emotion, in engineering action need to be addressed when teaching social responsibility within the engineering curriculum. After presenting reasons for this claim, I look at two different, but not mutually exclusive, approaches to address volitional…

  20. Cognitive Operations on Space and Their Impact on the Precision of Location Memory

    ERIC Educational Resources Information Center

    Lansdale, Mark; Humphries, Joyce; Flynn, Victoria

    2013-01-01

    Learning about object locations in space usually involves the summation of information from different experiences of that space and requires various cognitive operations to make this possible. These processes are poorly understood and, in the extreme, may not occur--leading to mutual exclusivity of memories (Baguley, Lansdale, Lines, & Parkin,…

  1. The Delaware Function Rater: A Method of Quantifying Classroom Behavior.

    ERIC Educational Resources Information Center

    Gaynor, John F.; Gaynor, Mary F.

    Developed was a student behavior rating system for use by teachers in identifying and assessing behavior problems and as an aid in classroom management. A time coding instrument was used, with behavior expressed as relative frequencies of a hierarchy of four mutually exclusive, exhaustive categories of behavior--relevent, unproductive, disruptive,…

  2. Mitigating budget constraints on visitation volume surveys: the case of U.S. National forests

    Treesearch

    Ashley E. Askew; Donald B.K. English; Stanley J. Zarnoch; Neelam C. Poudyal; J.M. Bowker

    2014-01-01

    Stratified random sampling (SRS) provides a scientifically based estimate of a population comprising mutually exclusive, homogenous subgroups. In the National Visitor Use Monitoring (NVUM) program, SRS is used to estimate recreation visitation and visitor characteristics across activities on National forests. However, with rising costs and declining budgets, carrying...

  3. Individualism, Nationalism, and Universalism: The Educational Ideals of Mordecai M. Kaplan's Philosophy of Jewish Education

    ERIC Educational Resources Information Center

    Ackerman, Ari

    2008-01-01

    This article will examine educational ideals by exploring the relation between the individual, the collective, and humanity in Kaplan's Jewish and educational philosophy. Generally the goals of individualism, nationalism, and universalism are seen as mutually exclusive. By contrast, Kaplan argues for the symbiotic relationship between…

  4. SNSAG5 IS AN ALTERNATIVE SURFACE ANTIGEN OF SARCOCYSTIS NEURONA STRAINS THAT IS MUTUALLY EXCLUSIVE TO SNSAG1

    USDA-ARS?s Scientific Manuscript database

    Sarcocystis neurona is an obligate intracellular parasite that causes equine protozoal myeloencephalitis (EPM). Previous work has identified a gene family of paralogous surface antigens in S. neurona called SnSAGs. These surface proteins are immunogenic in their host animals, and are therefore can...

  5. Hard Facts and Soft Skills

    ERIC Educational Resources Information Center

    Terego, Alex

    2009-01-01

    The argument now raging in academic circles pits those who espouse teaching 21st century skills against those who believe that schools should be teaching explicit and well-sequenced content. This debate has largely been framed as an either-or proposition. In this author's view, portraying this debate as one between two mutually exclusive sides…

  6. Non-Mutually Exclusive Deep Neural Network Classifier for Combined Modes of Bearing Fault Diagnosis.

    PubMed

    Duong, Bach Phi; Kim, Jong-Myon

    2018-04-07

    The simultaneous occurrence of various types of defects in bearings makes their diagnosis more challenging owing to the resultant complexity of the constituent parts of the acoustic emission (AE) signals. To address this issue, a new approach is proposed in this paper for the detection of multiple combined faults in bearings. The proposed methodology uses a deep neural network (DNN) architecture to effectively diagnose the combined defects. The DNN structure is based on the stacked denoising autoencoder non-mutually exclusive classifier (NMEC) method for combined modes. The NMEC-DNN is trained using data for a single fault and it classifies both single faults and multiple combined faults. The results of experiments conducted on AE data collected through an experimental test-bed demonstrate that the DNN achieves good classification performance with a maximum accuracy of 95%. The proposed method is compared with a multi-class classifier based on support vector machines (SVMs). The NMEC-DNN yields better diagnostic performance in comparison to the multi-class classifier based on SVM. The NMEC-DNN reduces the number of necessary data collections and improves the bearing fault diagnosis performance.

  7. Mutually exclusive signaling signatures define the hepatic and pancreatic progenitor cell lineage divergence

    PubMed Central

    Rodríguez-Seguel, Elisa; Mah, Nancy; Naumann, Heike; Pongrac, Igor M.; Cerdá-Esteban, Nuria; Fontaine, Jean-Fred; Wang, Yongbo; Chen, Wei; Andrade-Navarro, Miguel A.; Spagnoli, Francesca M.

    2013-01-01

    Understanding how distinct cell types arise from multipotent progenitor cells is a major quest in stem cell biology. The liver and pancreas share many aspects of their early development and possibly originate from a common progenitor. However, how liver and pancreas cells diverge from a common endoderm progenitor population and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we defined the molecular identity of liver and pancreas progenitors that were isolated from the mouse embryo at two time points, spanning the period when the lineage decision is made. The integration of temporal and spatial gene expression profiles unveiled mutually exclusive signaling signatures in hepatic and pancreatic progenitors. Importantly, we identified the noncanonical Wnt pathway as a potential developmental regulator of this fate decision and capable of inducing the pancreas program in endoderm and liver cells. Our study offers an unprecedented view of gene expression programs in liver and pancreas progenitors and forms the basis for formulating lineage-reprogramming strategies to convert adult hepatic cells into pancreatic cells. PMID:24013505

  8. Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization-dependent SUMOylation.

    PubMed

    Zimnik, Susan; Gaestel, Matthias; Niedenthal, Rainer

    2009-03-01

    Post-translational modifications control the physiological activity of the signal transducer and activator of transcription STAT1. While phosphorylation at tyrosine Y701 is a prerequisite for STAT1 dimerization, its SUMOylation represses the transcriptional activity. Recently, we have demonstrated that SUMOylation at lysine K703 inhibits the phosphorylation of nearby localized Y701 of STAT1. Here, we analysed the influence of phosphorylation of Y701 on SUMOylation of K703 in vivo. For that reason, an Ubc9/substrate dimerization-dependent SUMOylation (USDDS) system was developed, which consists of fusions of the SUMOylation substrate and of the SUMO-conjugating enzyme Ubc9 to the chemically activatable heterodimerization domains FKBP and FRB, respectively. When FKBP fusion proteins of STAT1, p53, CRSP9, FOS, CSNK2B, HES1, TCF21 and MYF6 are coexpressed with Ubc9-FRB, treatment of HEK293 cells with the rapamycin-related dimerizer compound AP21967 induces SUMOylation of these proteins in vivo. For STAT1-FKBP and p53-FKBP we show that this SUMOylation takes place at their specific SUMOylation sites in vivo. Using USDDS, we then demonstrate that STAT1 phosphorylation at Y701 induced by interferon-beta treatment inhibits SUMOylation of K703 in vivo. Thus, pY701 and SUMO-K703 of STAT1 represent mutually exclusive modifications, which prevent signal integration at this molecule and probably ensure the existence of differentially modified subpopulations of STAT1 necessary for its regulated nuclear cytoplasmic activation/inactivation cycle.

  9. Characterizing genomic differences of human cancer stratified by the TP53 mutation status.

    PubMed

    Wang, Mengyao; Yang, Chao; Zhang, Xiuqing; Li, Xiangchun

    2018-06-01

    The key roles of the TP53 mutation in cancer have been well established. TP53 is the most frequently mutated gene, and its inactivation is widespread among human cancer types. However, the landscape of genomic alterations in human cancers stratified by the TP53 mutation has not yet been described. We obtained somatic mutation and copy number change data of 6551 regular-mutated samples from the Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy number alterations, mutational signatures and mutational strand asymmetries between cancer samples with and without the TP53 mutation. We identified 126 SMGs, 30 of which were statistically significant in both the TP53 mutant and wild-type groups. Several SMGs, such as VHL, SMAD4 and PTEN, showed a mutation bias towards the TP53 wild-type group, whereas ATRX, IDH1 and RB1 were more prevalent in the TP53 mutant group. Five mutational signatures were extracted from the combined TCGA dataset on which mutational asymmetry analysis was performed, revealing that the TP53 mutant group exhibited substantially greater replication and transcription biases. Furthermore, we found that alterations of multiple genes in a merged mutually exclusive network composed of BRAF, EGFR, PAK1, PIK3CA, PTEN, APC and TERT were related to shortened survival in the TP53 wild-type group. In summary, we characterized the genomic differences and similarities underlying human cancers stratified by the TP53 mutation and identified multi-gene alterations of a merged mutually exclusive network to be a poor prognostic factor for the TP53 wild-type group.

  10. The Effect of Prior Knowledge Activation on Text Recall: An Investigation of Two Conflicting Hypotheses.

    ERIC Educational Resources Information Center

    Machiels-Bongaerts, Maureen; And Others

    Two hypotheses, the cognitive capacity hypothesis and the selective attention hypothesis, try to account for the facilitation effects of prior knowledge activation. They appear to be mutually exclusive since they predict different recall patterns as a result of prior knowledge activation. This study was designed to determine whether the two…

  11. Do Multielement Visual Tracking and Visual Search Draw Continuously on the Same Visual Attention Resources?

    ERIC Educational Resources Information Center

    Alvarez, George A.; Horowitz, Todd S.; Arsenio, Helga C.; DiMase, Jennifer S.; Wolfe, Jeremy M.

    2005-01-01

    Multielement visual tracking and visual search are 2 tasks that are held to require visual-spatial attention. The authors used the attentional operating characteristic (AOC) method to determine whether both tasks draw continuously on the same attentional resource (i.e., whether the 2 tasks are mutually exclusive). The authors found that observers…

  12. Toward a Sociology of Acceptance: The Other Side of the Study of Deviance.

    ERIC Educational Resources Information Center

    Bogdan, Robert; Taylor, Steven

    1987-01-01

    This article discusses the history of the sociology of deviance and the exclusion from society of individuals who do not meet norms, and argues for a sociology emphasizing acceptance of differences on individual, group, and societal levels. Types of relationships based on mutual acceptance are discussed along with generalizations regarding the…

  13. Using Statechart Assertion for the Formal Validation and Verification of a Real-Time Software System: A Case Study

    DTIC Science & Technology

    2011-03-01

    could be an entry point into a repeated task (or thread). The following example uses binary semaphores . The VxWorks operating system utilizes binary... semaphores via system calls: SemTake and SemGive. These semaphores are used primarily for mutual exclusion to protect resources from being accessed

  14. Environmental Education and Ecofeminist Pedagogy: Bridging the Environmental and the Social

    ERIC Educational Resources Information Center

    Harvester, Lara; Blenkinsop, Sean

    2010-01-01

    This paper begins by suggesting that issues of social and ecological justice are not mutually exclusive. They are tied together through the logic of domination which is, in turn, sustained by oppositional value dualisms such man/woman, human/nature, and white/non-white. As such, we suggest that environmental education must deal with the shared…

  15. Prevalence of Schizophrenia Spectrum Disorders in Average-IQ Adults with Autism Spectrum Disorders: A Meta-Analysis

    ERIC Educational Resources Information Center

    Lugo Marín, Jorge; Rodríguez-Franco, Montserrat Alviani; Mahtani Chugani, Vinita; Magán Maganto, María; Díez Villoria, Emiliano; Canal Bedia, Ricardo

    2018-01-01

    Since their separation as independent diagnostics, autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) have been conceptualized as mutually exclusive disorders. Similarities between both disorders can lead to misdiagnosis, especially when it comes to average-IQ adults who were not identified during childhood. The aim of this…

  16. Neutron Crystallography, Molecular Dynamics, and Quantum Mechanics Studies of the Nature of Hydrogen Bonding in Cellulose I beta

    USDA-ARS?s Scientific Manuscript database

    In the crystal structure of cellulose Ibeta, disordered hydrogen (H) bonding can be represented by the average of two mutually exclusive H bonding schemes that have been designated A and B. An unanswered question is whether A and B interconvert dynamically, or whether they are static but present in ...

  17. 47 CFR 27.1103 - 2000-2020 MHz and 2180-2200 MHz bands subject to competitive bidding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false 2000-2020 MHz and 2180-2200 MHz bands subject... MHz, 2000-2020 MHz, and 2180-2200 MHz bands Licensing and Competitive Bidding Provisions § 27.1103 2000-2020 MHz and 2180-2200 MHz bands subject to competitive bidding. Mutually exclusive initial...

  18. Feature Biases in Early Word Learning: Network Distinctiveness Predicts Age of Acquisition

    ERIC Educational Resources Information Center

    Engelthaler, Tomas; Hills, Thomas T.

    2017-01-01

    Do properties of a word's features influence the order of its acquisition in early word learning? Combining the principles of mutual exclusivity and shape bias, the present work takes a network analysis approach to understanding how feature distinctiveness predicts the order of early word learning. Distance networks were built from nouns with edge…

  19. The How and Why of Academic Collaboration: Disciplinary Differences and Policy Implications

    ERIC Educational Resources Information Center

    Lewis, Jenny M.; Ross, Sandy; Holden, Thomas

    2012-01-01

    This paper examines how and why academics in different parts of the academy collaborate. In this paper we argue that: (1) There is a useful analytical distinction to be made between collaboration (fluid and expressive) and Collaboration (concrete and instrumental); (2) These two are not mutually exclusive and their use varies between disciplines;…

  20. On the Uses of Cultural Knowledge

    DTIC Science & Technology

    2007-11-01

    awareness that a cultural understanding of an adversary society is imperative if counterinsurgency is to succeed. This monograph, by Dr. Sheila...cultural awareness and understanding of adversary societies has been widely recognized as essential to operations and tactics on the battlefield, Dr...levels of warfare—strategy, operations, and tactics. Although not mutually exclusive, cultural knowledge informs these distinct levels in different

  1. Gender, Race, and Justifications for Group Exclusion: Urban Black Students Bussed to Affluent Suburban Schools

    ERIC Educational Resources Information Center

    Ispa-Landa, Simone

    2013-01-01

    Relational theories of gender conceptualize masculinity and femininity as mutually constitutive. Using a relational approach, I analyzed ethnographic and interview data from male and female black adolescents in Grades 8 through 10 enrolled in ''Diversify,'' an urban-to-suburban racial integration program ("n" = 38).…

  2. Novel Labels Support 10-Month-Olds' Attention to Novel Objects

    ERIC Educational Resources Information Center

    Mather, Emily; Plunkett, Kim

    2010-01-01

    What is the source of the "mutual exclusivity" bias whereby infants map novel labels onto novel objects? In an intermodal preferential looking task, we found that novel labels support 10-month-olds' attention to a novel object over a familiar object. In contrast, familiar labels and a neutral phrase gradually reduced attention to a novel object.…

  3. The Group-lending Model and Social Closure: Microcredit, Exclusion, and Health in Bangladesh

    PubMed Central

    Johnston, Heidi Bart

    2009-01-01

    According to social exclusion theory, health risks are positively associated with involuntary social, economic, political and cultural exclusion from society. In this paper, a social exclusion framework has been used, and available literature on microcredit in Bangladesh has been reviewed to explore the available evidence on associations among microcredit, exclusion, and health outcomes. The paper addresses the question of whether participation in group-lending reduces health inequities through promoting social inclusion. The group-lending model of microcredit is a development intervention in which small-scale credit for income-generation activities is provided to groups of individuals who do not have material collateral. The paper outlines four pathways through which microcredit can affect health status: financing care in the event of health emergencies; financing health inputs such as improved nutrition; as a platform for health education; and by increasing social capital through group meetings and mutual support. For many participants, the group-lending model of microcredit can mitigate exclusionary processes and lead to improvements in health for some; for others, it can worsen exclusionary processes which contribute to health disadvantage. PMID:19761085

  4. The group-lending model and social closure: microcredit, exclusion, and health in Bangladesh.

    PubMed

    Schurmann, Anna T; Johnston, Heidi Bart

    2009-08-01

    According to social exclusion theory, health risks are positively associated with involuntary social, economic, political and cultural exclusion from society. In this paper, a social exclusion framework has been used, and available literature on microcredit in Bangladesh has been reviewed to explore the available evidence on associations among microcredit, exclusion, and health outcomes. The paper addresses the question of whether participation in group-lending reduces health inequities through promoting social inclusion. The group-lending model of microcredit is a development intervention in which small-scale credit for income-generation activities is provided to groups of individuals who do not have material collateral. The paper outlines four pathways through which microcredit can affect health status: financing care in the event of health emergencies; financing health inputs such as improved nutrition; as a platform for health education; and by increasing social capital through group meetings and mutual support. For many participants, the group-lending model of microcredit can mitigate exclusionary processes and lead to improvements in health for some; for others, it can worsen exclusionary processes which contribute to health disadvantage.

  5. The Curious Case of the Camelthorn: Competition, Coexistence, and Nest-Site Limitation in a Multispecies Mutualism.

    PubMed

    Campbell, Heather; Fellowes, Mark D E; Cook, James M

    2015-12-01

    Myrmecophyte plants house ants within domatia in exchange for protection against herbivores. Ant-myrmecophyte mutualisms exhibit two general patterns due to competition between ants for plant occupancy: (i) domatia nest sites are a limiting resource and (ii) each individual plant hosts one ant species at a time. However, individual camelthorn trees (Vachellia erioloba) typically host two to four ant species simultaneously, often coexisting in adjacent domatia on the same branch. Such fine-grain spatial coexistence brings into question the conventional wisdom on ant-myrmecophyte mutualisms. Camelthorn ants appear not to be nest-site limited, despite low abundance of suitable domatia, and have random distributions of nest sites within and across trees. These patterns suggest a lack of competition between ants for domatia and contrast strongly with other ant-myrmecophyte systems. Comparison of this unusual case with others suggests that spatial scale is crucial to coexistence or competitive exclusion involving multiple ant species. Furthermore, coexistence may be facilitated when co-occurring ant species diverge strongly on at least one niche axis. Our conclusions provide recommendations for future ant-myrmecophyte research, particularly in utilizing multispecies systems to further our understanding of mutualism biology.

  6. A Neural Model of Chromatic Induction in Uniform and Textured Images and Psychophysical Detection of Non-Opponent Chromatic Qualia

    ERIC Educational Resources Information Center

    Livitz, Gennady

    2011-01-01

    Color is a complex and rich perceptual phenomenon that relates physical properties of light to certain perceptual qualia associated with vision. Hering's opponent color theory, widely regarded as capturing the most fundamental aspects of color phenomenology, suggests that certain unique hues are mutually exclusive as components of a single color.…

  7. Maintaining Consistency in Distributed Systems

    DTIC Science & Technology

    1991-11-01

    type of 8 concurrency is readily controlled using synchronization tools such as monitors or semaphores . which are a standard part of most threads...sug- gested that these issues are often best solved using traditional synchronization constructs, such as monitors and semaphores , and that...data structures would normally arise within individual programs, and be controlled using mutual exclusion constructs, such as semaphores and monitors

  8. Impact of Contact on the Development of Children's Positive Stereotyping about Aging Language Competence

    ERIC Educational Resources Information Center

    Kwong See, Sheree T.; Nicoladis, Elena

    2010-01-01

    This study examined young children's (M = 38 months) beliefs about the aging of language competence using a modified mutual exclusivity paradigm (cf. Markman, 1990). Children were shown pairs of objects (familiar and unfamiliar) and were asked by a younger and older experimenter to point to the object in the pair to which a novel non-word…

  9. Speech Act Analysis of Instructional Communications Resulting from a Home-Based Learning Task: A Job Just Begun.

    ERIC Educational Resources Information Center

    Nicassio, Frank J.

    In order to establish an initial data source for elementary level home-based intervention programs, 18 dyads of second-graders and their parents were divided into three mutually exclusive achievement groups and observed while completing an instructional tool introduced into the home by the childs' school. Parent/child interactions were stimulated…

  10. A Missing Link in Suggestibility Research: What Is Known About the Behavior of Field Interviewers in Unstructured Interviews With Young Children?

    ERIC Educational Resources Information Center

    Gilstrap, Livia L.

    2004-01-01

    Despite suggestibility researchers' focus on adult behaviors that distort children's reports, whether behaviors examined in experimental work are used in the field is unknown. The current study presents a mutually exclusive and exhaustive hierarchical coding system that reflects interview questioning behaviors of concern in experimental work. The…

  11. Test Takers' Beliefs and Experiences of a High-Stakes Computer-Based English Listening and Speaking Test

    ERIC Educational Resources Information Center

    Zhan, Ying; Wan, Zhi Hong

    2016-01-01

    Test takers' beliefs or experiences have been overlooked in most validation studies in language education. Meanwhile, a mutual exclusion has been observed in the literature, with little or no dialogue between validation studies and studies concerning the uses and consequences of testing. To help fill these research gaps, a group of Senior III…

  12. Mingling "Fact" with "Fiction": Strategies for Integrating Literature into History and Social Studies Classrooms

    ERIC Educational Resources Information Center

    Turk, Diana B.; Klein, Emily; Dickstein, Shari

    2007-01-01

    In this article, the authors offer a series of strategies to help teachers integrate literature into their history and social studies classrooms without losing the flavor or essence of either the literature they are using or the history they are trying to teach. None of the presented approaches is mutually exclusive of the others, and several may…

  13. 47 CFR 27.1103 - 2000-2020 MHz and 2180-2200 MHz bands subject to competitive bidding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false 2000-2020 MHz and 2180-2200 MHz bands subject... Bidding Provisions § 27.1103 2000-2020 MHz and 2180-2200 MHz bands subject to competitive bidding. Mutually exclusive initial applications for 2000-2020 MHz and 2180-2200 MHz band licenses are subject to...

  14. An Alternative to Adaptation by Sexual Selection: Habitat Choice.

    PubMed

    Porter, Cody K; Akcali, Christopher K

    2018-06-09

    Adaptation in mating signals and preferences has generally been explained by sexual selection. We propose that adaptation in such mating traits might also arise via a non-mutually exclusive process wherein individuals preferentially disperse to habitats where they experience high mating performance. Here we explore the evolutionary implications of this process. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. EPDM polymers with intermolecular asymmetrical molecular weight, crystallinity and diene distribution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Datta, S.; Cheremishinoff, N.P.; Kresge, E.N.

    1993-12-31

    Rapid extrusion of EPDM elastomers require low viscosity and thus low molecular weights for the polymer. Efficient vulcanization of these elastomers requires network perfection and thus high molecular weights for the polymer. The benefits of these apparently mutually exclusive goals is important in uses of EPDM elastomers which require extrusion of profiles which are later cured. This paper shows that by introducing simultaneously asymmetry in the distribution of molecular weights, crystallinity and vulcanizable sites these apparently contradictory goals can be resolved. While these polymers cannot be made from a single Ziegler polymerization catalyst, the authors show the synthesis of thesemore » model EPDM polymers by blending polymers with very different molecular weights, ethylene and ENB contents. These blends can be rapidly extruded without melt fracture and can be cured to vulcanizates which have excellent tensile properties.« less

  16. Allostery Mediates Ligand Binding to Grb2 Adaptor in a Mutually Exclusive Manner

    PubMed Central

    McDonald, Caleb B.; El Hokayem, Jimmy; Zafar, Nawal; Balke, Jordan E.; Bhat, Vikas; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Farooq, Amjad

    2012-01-01

    Allostery plays a key role in dictating the stoichiometry and thermodynamics of multi-protein complexes driving a plethora of cellular processes central to health and disease. Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non-overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2-Sos1 and Grb2-Gab1 binary signaling complexes in concert in lieu of a composite Sos1-Grb2-Gab1 ternary complex. Of particular interest is the observation that the binding of Sos1 to the nSH3 domain within Grb2 sterically blocks the binding of Gab1 to the cSH3 domain and vice versa in a mutually exclusive manner. Importantly, the formation of both the Grb2-Sos1 and Grb2-Gab1 binary complexes is governed by a stoichiometry of 2:1, whereby the respective SH3 domains within Grb2 homodimer bind to Sos1 and Gab1 via multivalent interactions. Collectively, our study sheds new light on the role of allostery in mediating cellular signaling machinery. PMID:23334917

  17. Non-Mutually Exclusive Deep Neural Network Classifier for Combined Modes of Bearing Fault Diagnosis

    PubMed Central

    Kim, Jong-Myon

    2018-01-01

    The simultaneous occurrence of various types of defects in bearings makes their diagnosis more challenging owing to the resultant complexity of the constituent parts of the acoustic emission (AE) signals. To address this issue, a new approach is proposed in this paper for the detection of multiple combined faults in bearings. The proposed methodology uses a deep neural network (DNN) architecture to effectively diagnose the combined defects. The DNN structure is based on the stacked denoising autoencoder non-mutually exclusive classifier (NMEC) method for combined modes. The NMEC-DNN is trained using data for a single fault and it classifies both single faults and multiple combined faults. The results of experiments conducted on AE data collected through an experimental test-bed demonstrate that the DNN achieves good classification performance with a maximum accuracy of 95%. The proposed method is compared with a multi-class classifier based on support vector machines (SVMs). The NMEC-DNN yields better diagnostic performance in comparison to the multi-class classifier based on SVM. The NMEC-DNN reduces the number of necessary data collections and improves the bearing fault diagnosis performance. PMID:29642466

  18. A high performance totally ordered multicast protocol

    NASA Technical Reports Server (NTRS)

    Montgomery, Todd; Whetten, Brian; Kaplan, Simon

    1995-01-01

    This paper presents the Reliable Multicast Protocol (RMP). RMP provides a totally ordered, reliable, atomic multicast service on top of an unreliable multicast datagram service such as IP Multicasting. RMP is fully and symmetrically distributed so that no site bears un undue portion of the communication load. RMP provides a wide range of guarantees, from unreliable delivery to totally ordered delivery, to K-resilient, majority resilient, and totally resilient atomic delivery. These QoS guarantees are selectable on a per packet basis. RMP provides many communication options, including virtual synchrony, a publisher/subscriber model of message delivery, an implicit naming service, mutually exclusive handlers for messages, and mutually exclusive locks. It has commonly been held that a large performance penalty must be paid in order to implement total ordering -- RMP discounts this. On SparcStation 10's on a 1250 KB/sec Ethernet, RMP provides totally ordered packet delivery to one destination at 842 KB/sec throughput and with 3.1 ms packet latency. The performance stays roughly constant independent of the number of destinations. For two or more destinations on a LAN, RMP provides higher throughput than any protocol that does not use multicast or broadcast.

  19. A minimal model for multiple epidemics and immunity spreading.

    PubMed

    Sneppen, Kim; Trusina, Ala; Jensen, Mogens H; Bornholdt, Stefan

    2010-10-18

    Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

  20. The devil to pay: a cost of mutualism with Myrmelachista schumanni ants in ‘devil's gardens’ is increased herbivory on Duroia hirsuta trees

    PubMed Central

    Frederickson, Megan E; Gordon, Deborah M

    2007-01-01

    ‘Devil's gardens’ are nearly pure stands of the myrmecophyte, Duroia hirsuta, that occur in Amazonian rainforests. Devil's gardens are created by Myrmelachista schumanni ants, which nest in D. hirsuta trees and kill other plants using formic acid as an herbicide. Here, we show that this ant–plant mutualism has an associated cost; by making devil's gardens, M. schumanni increases herbivory on D. hirsuta. We measured standing leaf herbivory on D. hirsuta trees and found that they sustain higher herbivory inside than outside devil's gardens. We also measured the rate of herbivory on nursery-grown D. hirsuta saplings planted inside and outside devil's gardens in ant-exclusion and control treatments. We found that when we excluded ants, herbivory on D. hirsuta was higher inside than outside devil's gardens. These results suggest that devil's gardens are a concentrated resource for herbivores. Myrmelachista schumanni workers defend D. hirsuta against herbivores, but do not fully counterbalance the high herbivore pressure in devil's gardens. We suggest that high herbivory may limit the spread of devil's gardens, possibly explaining why devil's gardens do not overrun Amazonian rainforests. PMID:17301016

  1. The devil to pay: a cost of mutualism with Myrmelachista schumanni ants in 'devil's gardens' is increased herbivory on Duroia hirsuta trees.

    PubMed

    Frederickson, Megan E; Gordon, Deborah M

    2007-04-22

    'Devil's gardens' are nearly pure stands of the myrmecophyte, Duroia hirsuta, that occur in Amazonian rainforests. Devil's gardens are created by Myrmelachista schumanni ants, which nest in D. hirsuta trees and kill other plants using formic acid as an herbicide. Here, we show that this ant-plant mutualism has an associated cost; by making devil's gardens, M. schumanni increases herbivory on D. hirsuta. We measured standing leaf herbivory on D. hirsuta trees and found that they sustain higher herbivory inside than outside devil's gardens. We also measured the rate of herbivory on nursery-grown D. hirsuta saplings planted inside and outside devil's gardens in ant-exclusion and control treatments. We found that when we excluded ants, herbivory on D. hirsuta was higher inside than outside devil's gardens. These results suggest that devil's gardens are a concentrated resource for herbivores. Myrmelachista schumanni workers defend D. hirsuta against herbivores, but do not fully counterbalance the high herbivore pressure in devil's gardens. We suggest that high herbivory may limit the spread of devil's gardens, possibly explaining why devil's gardens do not overrun Amazonian rainforests.

  2. Synchronization of Concurrent Processes

    DTIC Science & Technology

    1975-07-01

    Pettersen Stanford Ur.iversity Artificial Intelligence Laboratory ABSTRACT Th oaoer gives an overview of commonly used synchronization primitives and...wr.ters . ut.l.z.ng the DroDo4d synchronization primitive . The solution is simpler and shorter than other known S’ms The first sections of the paper...un reicr»» side il nrcttaary and Identity by block number) Scheduling, process scheduling, synchronization , mutual exclusion, semaphores , critical

  3. Multiple Labels for Objects in Conversations with Young Children: Parents' Language and Children's Developing Expectations about Word Meanings

    ERIC Educational Resources Information Center

    Callanan, Maureen A.; Sabbagh, Mark A.

    2004-01-01

    Children sometimes seem to expect words to have mutually exclusive meanings in certain contexts of early word learning. In 2 studies, 12- to 24-month-old children and their parents were videotaped as they engaged in conversations while playing with sets of toys (sea creatures, vehicles, doll clothing) in free-play, storytelling, and categorization…

  4. Bias and Undermatching in Delinquent Boys' Verbal Behavior as a Function of Their Level of Deviance

    ERIC Educational Resources Information Center

    McDowell, J. J.; Caron, Marcia L.

    2010-01-01

    Eighty-one 13- to 14-year-old boys at risk for delinquency (target boys) engaged in brief dyadic conversations with their peer friends. The target boys' verbal behavior was coded into two mutually exclusive content categories, rule-break talk and normative talk. Positive social responses from peer boys for each category of talk were also recorded,…

  5. Putting time into proof outlines

    NASA Technical Reports Server (NTRS)

    Schneider, Fred B.; Bloom, Bard; Marzullo, Keith

    1993-01-01

    A logic for reasoning about timing properties of concurrent programs is presented. The logic is based on Hoare-style proof outlines and can handle maximal parallelism as well as certain resource-constrained execution environments. The correctness proof for a mutual exclusion protocol that uses execution timings in a subtle way illustrates the logic in action. A soundness proof using structural operational semantics is outlined in the appendix.

  6. A Latent Class Analysis of Weight-Related Health Behaviors among 2-and 4-Year College Students and Associated Risk of Obesity

    ERIC Educational Resources Information Center

    Mathur, Charu; Stigler, Melissa; Lust, Katherine; Laska, Melissa

    2014-01-01

    Little is known about the complex patterning of weight-related health behaviors in 2-and 4-year college students. The objective of this study was to identify and describe unique classes of weight-related health behaviors among college students. Latent class analysis was used to identify homogenous, mutually exclusive classes of nine health…

  7. Assessing the paradigm of mutually exclusive erosion and deposition of mud, with examples from upper Chesapeake Bay

    USGS Publications Warehouse

    Sanford, L.P.; Halka, J.P.

    1993-01-01

    A paradigm of cohesive sediment transport research is that erosion and deposition are mutually exclusive. Many laboratory studies have shown that there is a velocity/stress threshold below which erosion does not occur and a lower threshold above which deposition does not occur. In contrast, a deposition threshold is not included in standard noncohesive sediment transport models, allowing erosion and deposition to occur simultaneously. Several researchers have also modeled erosion and deposition of mud without a deposition threshold. This distinction can have important implications for suspended sediment transport predictions and for data interpretation. Model-data comparisons based on observations of in situ erosion and deposition of upper Chesapeake Bay mud indicate poor agreement when the sediments are modeled as a single resuspended particle class and mutually exclusive erosion and deposition is assumed. The total resuspended sediment load increases in conjunction with increasing bottom shear stress as anticipated, but deposition is initiated soon after the shear stress begins to decrease and long before the stress falls below the value at which erosion had previously begun. Models assuming no critical stress for deposition, with continuous deposition proportional to the near bottom resuspended sediment concentration, describe the data better. Empirical parameter values estimated from these model fits are similar to other published values for estuarine cohesive sediments, indicating significantly greater erodability for higher water content surface sediments and settling velocities appropriate for large estuarine flocs. The apparent failure of the cohesive paradigm when applied to in situ data does not mean that the concept of a critical stress for deposition is wrong. Two possibilities for explaining the observed discrepancies are that certain aspects of in situ conditions have not been replicated in the laboratory experiments underlying the cohesive paradigm, and that in situ sediment behavior is better described as a sequence of particle classes than as the single particle class modeled here. However, the in situ measurements needed to resolve these questions are very difficult and data generally are not available. For practical modeling purposes, allowing continuous deposition of a single resuspended particle class may often give quite satisfactory results. ?? 1993.

  8. Visual attention spreads broadly but selects information locally.

    PubMed

    Shioiri, Satoshi; Honjyo, Hajime; Kashiwase, Yoshiyuki; Matsumiya, Kazumichi; Kuriki, Ichiro

    2016-10-19

    Visual attention spreads over a range around the focus as the spotlight metaphor describes. Spatial spread of attentional enhancement and local selection/inhibition are crucial factors determining the profile of the spatial attention. Enhancement and ignorance/suppression are opposite effects of attention, and appeared to be mutually exclusive. Yet, no unified view of the factors has been provided despite their necessity for understanding the functions of spatial attention. This report provides electroencephalographic and behavioral evidence for the attentional spread at an early stage and selection/inhibition at a later stage of visual processing. Steady state visual evoked potential showed broad spatial tuning whereas the P3 component of the event related potential showed local selection or inhibition of the adjacent areas. Based on these results, we propose a two-stage model of spatial attention with broad spread at an early stage and local selection at a later stage.

  9. Artistic creativity, artistic production, and aging.

    PubMed

    Mazzucchi, Anna; Sinforiani, Elena; Boller, François

    2013-01-01

    This chapter reviews the changes produced by age on various aspects of artistic painting, particularly creativity and actual production. Aging in trained painters is often accompanied by a decline in creativity, which in turn is due to the cognitive decline related to aging. It has been argued, however, that aging does not cause a decline, but only changes in style and content. The two views are not mutually exclusive, and we present examples illustrating both aspects. We also show that, in addition to cognitive changes, impairment of sensory organs, especially vision, and of the bones and joints, may also produce marked changes in an artist's production and style. We conclude by showing that finding ways to induce creativity in persons who do not consider themselves artists can be a way of stimulating creativity and contribute to successful aging. © 2013 Elsevier B.V. All rights reserved.

  10. A Risk-Continuum Categorization of Product Use Among US Youth Tobacco Users

    PubMed Central

    El-Toukhy, Sherine

    2016-01-01

    Introduction: To examine prevalence and correlates of five mutually exclusive tobacco-use patterns among US youth tobacco users. Methods: A nationally representative sample of tobacco users (N = 3202, 9–17 years) was classified into five product-use patterns. Weighted multinominal and multivariate logistic regression models were used to examine prevalence of product-use patterns by gender, race and ethnicity, and grade level; and associations between product-use patterns and perceived accessibility of tobacco products, exposure and receptivity to pro-tobacco marketing, social benefits of smoking, and tobacco-associated risks. Results: Dual use (ie, use of two product categories) was the most prevalent pattern (30.5%), followed by non-cigarette combustible only (26.7%), polytobacco (ie, use of three product categories; 17.5%), cigarette only (14.9%), and noncombustible only (10.4%) use. Product-use patterns differed by gender, race, and ethnicity. Compared to cigarette only users, dual and polytobacco users were more likely to be exposed to and be receptive to pro-tobacco marketing, and were less likely to acknowledge tobacco-use related risks (Ps < .05). Conclusions: Curbing tobacco use warrants research on users of more than one tobacco-product categories according to the risk-continuum categorization. Implications: We present a risk-continuum categorization of product-use patterns among tobacco users not older than 17 years. We classify tobacco users into five mutually exclusive product-use patterns: cigarette only users, non-cigarette combustible only users, noncombustible only users, dual use, and polytobacco use. This categorization overcomes limitations in current literature on tobacco-use patterns, which include exclusion of certain products (eg, e-cigarettes) and product-use patterns (eg, exclusive users of non-cigarette products), and inconsistent classification of tobacco users. It is parsimonious yet complex enough to retain differential characteristics of sub-tobacco users based on number (single, dual, polytobacco) and categories (cigarettes, non-cigarette combustibles, noncombustibles) of tobacco products consumed. PMID:26764258

  11. Amenable to reason: Aristotle's rhetoric and the moral psychology of practical ethics.

    PubMed

    London, A J

    2000-12-01

    An Aristotelian conception of practical ethics can be derived from the account of practical reasoning that Aristotle articulates in is Rhetoric and this has important implications for the way we understand the nature and limits of practical ethics. an important feature of this conception of practical ethics is its responsiveness to the complex ways in which agents form and maintain moral commitments, and this has important implications for the debate concerning methods of ethics in applied ethics. In particular, this feature enables us to understand casuistry, narrative, and principlism as mutually supportive modes of moral inquiry, rather than divergent and mutually exclusive methods of ethics. As a result, an Aristotelian conception of practical ethics clears the conceptual common ground upon which practical ethicists can forge a stable and realistic self-understanding.

  12. Seasonal sexual segregation in two Thalassarche albatross species: competitive exclusion, reproductive role specialization or foraging niche divergence?

    PubMed

    Phillips, R A; Silk, J R D; Phalan, B; Catry, P; Croxall, J P

    2004-06-22

    Sexual segregation by micro- or macrohabitat is common in birds, and usually attributed to size-mediated dominance and exclusion of females by larger males, trophic niche divergence or reproductive role specialization. Our study of black-browed albatrosses, Thalassarche melanophrys, and grey-headed albatrosses, T. chrysostoma, revealed an exceptional degree of sexual segregation during incubation, with largely mutually exclusive core foraging ranges for each sex in both species. Spatial segregation was not apparent during brood-guard or post-guard chick rearing, when adults are constrained to feed close to colonies, providing no evidence for dominance-related competitive exclusion at the macrohabitat level. A comprehensive morphometric comparison indicated considerable species and sexual dimorphism in wing area and wing loading that corresponded, both within and between species, to broad-scale habitat preferences relating to wind strength. We suggest that seasonal sexual segregation in these two species is attributable to niche divergence mediated by differences in flight performance. Such sexual segregation may also have implications for conservation in relation to sex-specific overlap with commercial fisheries.

  13. A, E, I, O, U and Always Y: A Simple Technique for Improving Communication and Assessment in the Mathematics Classroom

    ERIC Educational Resources Information Center

    Vazquez, Lorna Thomas

    2008-01-01

    This article describes the A, E, I, O, U technique, designed to help teachers ensure that teaching and learning are not mutually exclusive in the classroom. Most teachers would agree that motivating average teenagers to communicate how they got an answer or justify their problem-solving strategies can be as difficult as teaching a dog to whistle.…

  14. Synthesis, Interdiction, and Protection of Layered Networks

    DTIC Science & Technology

    2009-09-01

    152 4.7 Al Qaeda Network from Sageman Database . . . . . . . . . . 157 4.8 Interdiction Resources versus Closeness Centrality . . . . . . 159...where S may be a polyhedron , a set with discrete variables, a set with nonlin- earities, or so on); and partitions it into two mutually exclusive subsets...p. vii]. However, this database is based on Dr. Sagemans’s 2004 publication and may be dated. Therefore, the analysis in this section is to

  15. Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

    DTIC Science & Technology

    2017-12-01

    meaning that most men with prostate cancer have multiple, genetically distinct cancers. Pathologists cannot assess clonality by routine microscopic...Hence, in this proposal we utilized dual ERG/SPINK1 immunohistochemistry (IHC)—as a readout of clonal, mutually exclusive molecular subtypes—to assess...multiclonal (also referred to as multifocal), meaning that more than 80% of men with prostate cancer actually have multiple, genetically distinct

  16. Using Object-Oriented Databases for Implementation of Interactive Electronic Technical Manuals

    DTIC Science & Technology

    1992-03-01

    analytical process applied throughout the system acquisition program in order to define supportability related design factors and to ensure development of a...Node Alternatives Node Alternatives (NODEALTS) is a list of mutually exclusive nodes, grouped together by the fact that they apply to different...contextual situations. The content specific layer NODEALTS element is a reference to a set of nodes that might apply in different situations. No hierarchy

  17. U.S. Space Policy and Space Industry Strangulation

    DTIC Science & Technology

    2010-03-01

    protecting U.S. national security, and creating an environment in which non-U.S. citizens can participate fully in the U.S. space industry. 14...still protecting U.S. national security, and creating an environment in which non-U.S. citizens can participate fully in the U.S. space industry...security, and creating and sustaining a globally competitive space industry. These realms are not mutually exclusive. If technologies are overly guarded

  18. Voices Crying in the Wilderness: A Comparison of Pro-Boers and Anti- Imperialists, 1899-1902

    DTIC Science & Technology

    1991-05-01

    subordinate relationship to the national office. Its activities remained the same, however, and it continued to dominate the direction of the movement...repugnant, yet mutually exclusive, options confronted Blacks. First, an obvious consanguinity figuratively linked Filipinos and Blacks. Soldiers calling...more than a reaction to arbitrary military despotism. For some time the basic relationship between the home .:ountry and some colonies, the "white

  19. Quantifying short run cost-effectiveness during a gradual implementation process.

    PubMed

    van de Wetering, Gijs; Woertman, Willem H; Verbeek, Andre L; Broeders, Mireille J; Adang, Eddy M M

    2013-12-01

    This paper examines the short run inefficiencies that arise during gradual implementation of a new cost-effective technology in healthcare. These inefficiencies arise when health gains associated with the new technology cannot be obtained immediately because the new technology does not yet supply all patients, and when there is overcapacity for the old technology in the short run because the supply of care is divided among two mutually exclusive technologies. Such efficiency losses are not taken into account in standard textbook cost-effectiveness analysis in which a steady state is presented where costs and effects are assumed to be unchanging over time. A model is constructed to quantify such short run inefficiencies as well as to inform the decision maker about the optimal implementation pattern for the new technology. The model operates by integrating the incremental net benefit equations for both the period of co-existence of mutually exclusive technologies and the period after complete substitution of the old technology. It takes into account the rate of implementation of the new technology, depreciation of capital of the old technology as well as the demand curves for both technologies. The model is applied to the real world case of converting from screen film to digital mammography in the Netherlands.

  20. Sulfur dioxide-hydrogen peroxide relationships in clean air, clouds, and precipitation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schwartz, S.E.; Daum, P.H.

    1988-01-01

    In-cloud oxidation by H/sub 2/O/sub 2/ is a major route for conversion of atmospheric SO/sub 2/ to sulfate, as indicated by kinetic calculations for representative H/sub 2/O/sub 2/ concentrations and supported by the observation of mutual exclusivity of gaseous SO/sub 2/ and aqueous H/sub 2/O/sub 2/ in non-precipitating liquid-water stratiform clouds, which generally persist sufficiently for reaction to proceed to completion. Measurements reported here indicate the aqueous S(IV) and H/sub 2/O/sub 2/ are also mutually exclusive in surface precipitation samples, but that SO/sub 2/ and aqueous H/sub 2/O/sub 2/ often coexist in precipitating clouds. Gaseous SO/sub 2/ and H/sub 2/O/submore » 2/ are also commonly simultaneously present in clear air; in the mixed layer either species maybe in excess, but H/sub 2/O/sub 2/ present with SO/sub 2/ in precipitating clouds is attributed to material dissolved in falling hydrometeors which has not had time to react with SO/sub 2/. This supported by model calculations evaluating the characteristic time and distance for reaction of aqueous H/sub 2/O/sub 2/ in droplets falling through an SO/sub 2/-containing layer. 29 refs., 6 figs.« less

  1. A Tutorial on Multilevel Survival Analysis: Methods, Models and Applications

    PubMed Central

    Austin, Peter C.

    2017-01-01

    Summary Data that have a multilevel structure occur frequently across a range of disciplines, including epidemiology, health services research, public health, education and sociology. We describe three families of regression models for the analysis of multilevel survival data. First, Cox proportional hazards models with mixed effects incorporate cluster-specific random effects that modify the baseline hazard function. Second, piecewise exponential survival models partition the duration of follow-up into mutually exclusive intervals and fit a model that assumes that the hazard function is constant within each interval. This is equivalent to a Poisson regression model that incorporates the duration of exposure within each interval. By incorporating cluster-specific random effects, generalised linear mixed models can be used to analyse these data. Third, after partitioning the duration of follow-up into mutually exclusive intervals, one can use discrete time survival models that use a complementary log–log generalised linear model to model the occurrence of the outcome of interest within each interval. Random effects can be incorporated to account for within-cluster homogeneity in outcomes. We illustrate the application of these methods using data consisting of patients hospitalised with a heart attack. We illustrate the application of these methods using three statistical programming languages (R, SAS and Stata). PMID:29307954

  2. Generating effective project scheduling heuristics by abstraction and reconstitution

    NASA Technical Reports Server (NTRS)

    Janakiraman, Bhaskar; Prieditis, Armand

    1992-01-01

    A project scheduling problem consists of a finite set of jobs, each with fixed integer duration, requiring one or more resources such as personnel or equipment, and each subject to a set of precedence relations, which specify allowable job orderings, and a set of mutual exclusion relations, which specify jobs that cannot overlap. No job can be interrupted once started. The objective is to minimize project duration. This objective arises in nearly every large construction project--from software to hardware to buildings. Because such project scheduling problems are NP-hard, they are typically solved by branch-and-bound algorithms. In these algorithms, lower-bound duration estimates (admissible heuristics) are used to improve efficiency. One way to obtain an admissible heuristic is to remove (abstract) all resources and mutual exclusion constraints and then obtain the minimal project duration for the abstracted problem; this minimal duration is the admissible heuristic. Although such abstracted problems can be solved efficiently, they yield inaccurate admissible heuristics precisely because those constraints that are central to solving the original problem are abstracted. This paper describes a method to reconstitute the abstracted constraints back into the solution to the abstracted problem while maintaining efficiency, thereby generating better admissible heuristics. Our results suggest that reconstitution can make good admissible heuristics even better.

  3. Epigenetic Silencing of Plasmodium falciparum Genes Linked to Erythrocyte Invasion

    PubMed Central

    Cortés, Alfred; Carret, Celine; Kaneko, Osamu; Yim Lim, Brian Y. S.; Ivens, Alasdair; Holder, Anthony A

    2007-01-01

    The process of erythrocyte invasion by merozoites of Plasmodium falciparum involves multiple steps, including the formation of a moving junction between parasite and host cell, and it is characterised by the redundancy of many of the receptor–ligand interactions involved. Several parasite proteins that interact with erythrocyte receptors or participate in other steps of invasion are encoded by small subtelomerically located gene families of four to seven members. We report here that members of the eba, rhoph1/clag, acbp, and pfRh multigene families exist in either an active or a silenced state. In the case of two members of the rhoph1/clag family, clag3.1 and clag3.2, expression was mutually exclusive. Silencing was clonally transmitted and occurred in the absence of detectable DNA alterations, suggesting that it is epigenetic. This was demonstrated for eba-140. Our data demonstrate that variant or mutually exclusive expression and epigenetic silencing in Plasmodium are not unique to genes such as var, which encode proteins that are exported to the surface of the erythrocyte, but also occur for genes involved in host cell invasion. Clonal variant expression of invasion-related ligands increases the flexibility of the parasite to adapt to its human host. PMID:17676953

  4. A Tutorial on Multilevel Survival Analysis: Methods, Models and Applications.

    PubMed

    Austin, Peter C

    2017-08-01

    Data that have a multilevel structure occur frequently across a range of disciplines, including epidemiology, health services research, public health, education and sociology. We describe three families of regression models for the analysis of multilevel survival data. First, Cox proportional hazards models with mixed effects incorporate cluster-specific random effects that modify the baseline hazard function. Second, piecewise exponential survival models partition the duration of follow-up into mutually exclusive intervals and fit a model that assumes that the hazard function is constant within each interval. This is equivalent to a Poisson regression model that incorporates the duration of exposure within each interval. By incorporating cluster-specific random effects, generalised linear mixed models can be used to analyse these data. Third, after partitioning the duration of follow-up into mutually exclusive intervals, one can use discrete time survival models that use a complementary log-log generalised linear model to model the occurrence of the outcome of interest within each interval. Random effects can be incorporated to account for within-cluster homogeneity in outcomes. We illustrate the application of these methods using data consisting of patients hospitalised with a heart attack. We illustrate the application of these methods using three statistical programming languages (R, SAS and Stata).

  5. SU-E-J-179: Prediction of Pelvic Nodal Coverage Using Mutual Information Between Cone-Beam and Planning CTs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jani, S; Kishan, A; O'Connell, D

    2014-06-01

    Purpose: To investigate if pelvic nodal coverage for prostate patients undergoing intensity modulated radiotherapy (IMRT) can be predicted using mutual image information computed between planning and cone-beam CTs (CBCTs). Methods: Four patients with high-risk prostate adenocarcinoma were treated with IMRT on a Varian TrueBeam. Plans were designed such that 95% of the nodal planning target volume (PTV) received the prescription dose of 45 Gy (N=1) or 50.4 Gy (N=3). Weekly CBCTs (N=25) were acquired and the nodal clinical target volumes and organs at risk were contoured by a physician. The percent nodal volume receiving prescription dose was recorded as amore » ground truth. Using the recorded shifts performed by the radiation therapists at the time of image acquisition, CBCTs were aligned with the planning kVCT. Mutual image information (MI) was calculated between the CBCT and the aligned planning CT within the contour of the nodal PTV. Due to variable CBCT fields-of-view, CBCT images covering less than 90% of the nodal volume were excluded from the analysis, resulting in the removal of eight CBCTs. Results: A correlation coefficient of 0.40 was observed between the MI metric and the percent of the nodal target volume receiving the prescription dose. One patient's CBCTs had clear outliers from the rest of the patients. Upon further investigation, we discovered image artifacts that were present only in that patient's images. When those four images were excluded, the correlation improved to 0.81. Conclusion: This pilot study shows the potential of predicting pelvic nodal dosimetry by computing the mutual image information between planning CTs and patient setup CBCTs. Importantly, this technique does not involve manual or automatic contouring of the CBCT images. Additional patients and more robust exclusion criteria will help validate our findings.« less

  6. Sensitivity analysis in a Lassa fever deterministic mathematical model

    NASA Astrophysics Data System (ADS)

    Abdullahi, Mohammed Baba; Doko, Umar Chado; Mamuda, Mamman

    2015-05-01

    Lassa virus that causes the Lassa fever is on the list of potential bio-weapons agents. It was recently imported into Germany, the Netherlands, the United Kingdom and the United States as a consequence of the rapid growth of international traffic. A model with five mutually exclusive compartments related to Lassa fever is presented and the basic reproduction number analyzed. A sensitivity analysis of the deterministic model is performed. This is done in order to determine the relative importance of the model parameters to the disease transmission. The result of the sensitivity analysis shows that the most sensitive parameter is the human immigration, followed by human recovery rate, then person to person contact. This suggests that control strategies should target human immigration, effective drugs for treatment and education to reduced person to person contact.

  7. The shield effect: nuptial gifts protect males against pre-copulatory sexual cannibalism

    PubMed Central

    Albo, Maria J.

    2016-01-01

    Several not mutually exclusive functions have been ascribed to nuptial gifts across different taxa. Although the idea that a nuptial prey gift may protect the male from pre-copulatory sexual cannibalism is attractive, it has previously been considered of no importance based on indirect evidence and rejected by experimental tests. We reinvestigated whether nuptial gifts may function as a shield against female attacks during mating encounters in the spider Pisaura mirabilis and whether female hunger influences the likelihood of cannibalistic attacks. The results showed that pre-copulatory sexual cannibalism was enhanced when males courted without a gift and this was independent of female hunger. We propose that the nuptial gift trait has evolved partly as a counteradaptation to female aggression in this spider species. PMID:27194284

  8. The shield effect: nuptial gifts protect males against pre-copulatory sexual cannibalism.

    PubMed

    Toft, Søren; Albo, Maria J

    2016-05-01

    Several not mutually exclusive functions have been ascribed to nuptial gifts across different taxa. Although the idea that a nuptial prey gift may protect the male from pre-copulatory sexual cannibalism is attractive, it has previously been considered of no importance based on indirect evidence and rejected by experimental tests. We reinvestigated whether nuptial gifts may function as a shield against female attacks during mating encounters in the spider Pisaura mirabilis and whether female hunger influences the likelihood of cannibalistic attacks. The results showed that pre-copulatory sexual cannibalism was enhanced when males courted without a gift and this was independent of female hunger. We propose that the nuptial gift trait has evolved partly as a counteradaptation to female aggression in this spider species. © 2016 The Author(s).

  9. Structural basis for signaling by exclusive EDS1 heteromeric complexes with SAG101 or PAD4 in plant innate immunity.

    PubMed

    Wagner, Stephan; Stuttmann, Johannes; Rietz, Steffen; Guerois, Raphael; Brunstein, Elena; Bautor, Jaqueline; Niefind, Karsten; Parker, Jane E

    2013-12-11

    Biotrophic plant pathogens encounter a postinfection basal resistance layer controlled by the lipase-like protein enhanced disease susceptibility 1 (EDS1) and its sequence-related interaction partners, senescence-associated gene 101 (SAG101) and phytoalexin deficient 4 (PAD4). Maintainance of separate EDS1 family member clades through angiosperm evolution suggests distinct functional attributes. We report the Arabidopsis EDS1-SAG101 heterodimer crystal structure with juxtaposed N-terminal α/β hydrolase and C-terminal α-helical EP domains aligned via a large conserved interface. Mutational analysis of the EDS1-SAG101 heterodimer and a derived EDS1-PAD4 structural model shows that EDS1 signals within mutually exclusive heterocomplexes. Although there is evolutionary conservation of α/β hydrolase topology in all three proteins, a noncatalytic resistance mechanism is indicated. Instead, the respective N-terminal domains appear to facilitate binding of the essential EP domains to create novel interaction surfaces on the heterodimer. Transitions between distinct functional EDS1 heterodimers might explain the central importance and versatility of this regulatory node in plant immunity. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site.

    PubMed

    Nguyen, Thi Hoang Duong; Li, Jade; Galej, Wojciech P; Oshikane, Hiroyuki; Newman, Andrew J; Nagai, Kiyoshi

    2013-06-04

    The U5 small nuclear ribonucleoprotein particle (snRNP) helicase Brr2 disrupts the U4/U6 small nuclear RNA (snRNA) duplex and allows U6 snRNA to engage in an intricate RNA network at the active center of the spliceosome. Here, we present the structure of yeast Brr2 in complex with the Jab1/MPN domain of Prp8, which stimulates Brr2 activity. Contrary to previous reports, our crystal structure and mutagenesis data show that the Jab1/MPN domain binds exclusively to the N-terminal helicase cassette. The residues in the Jab1/MPN domain, whose mutations in human Prp8 cause the degenerative eye disease retinitis pigmentosa, are found at or near the interface with Brr2, clarifying its molecular pathology. In the cytoplasm, Prp8 forms a precursor complex with U5 snRNA, seven Smproteins, Snu114, and Aar2, but after nuclear import, Brr2 replaces Aar2 to form mature U5 snRNP. Our structure explains why Aar2 and Brr2 are mutually exclusive and provides important insights into the assembly of U5 snRNP.

  11. Detecting and overcoming systematic errors in genome-scale phylogenies.

    PubMed

    Rodríguez-Ezpeleta, Naiara; Brinkmann, Henner; Roure, Béatrice; Lartillot, Nicolas; Lang, B Franz; Philippe, Hervé

    2007-06-01

    Genome-scale data sets result in an enhanced resolution of the phylogenetic inference by reducing stochastic errors. However, there is also an increase of systematic errors due to model violations, which can lead to erroneous phylogenies. Here, we explore the impact of systematic errors on the resolution of the eukaryotic phylogeny using a data set of 143 nuclear-encoded proteins from 37 species. The initial observation was that, despite the impressive amount of data, some branches had no significant statistical support. To demonstrate that this lack of resolution is due to a mutual annihilation of phylogenetic and nonphylogenetic signals, we created a series of data sets with slightly different taxon sampling. As expected, these data sets yielded strongly supported but mutually exclusive trees, thus confirming the presence of conflicting phylogenetic and nonphylogenetic signals in the original data set. To decide on the correct tree, we applied several methods expected to reduce the impact of some kinds of systematic error. Briefly, we show that (i) removing fast-evolving positions, (ii) recoding amino acids into functional categories, and (iii) using a site-heterogeneous mixture model (CAT) are three effective means of increasing the ratio of phylogenetic to nonphylogenetic signal. Finally, our results allow us to formulate guidelines for detecting and overcoming phylogenetic artefacts in genome-scale phylogenetic analyses.

  12. Nonrandom Composition of Flower Colors in a Plant Community: Mutually Different Co-Flowering Natives and Disturbance by Aliens

    PubMed Central

    Makino, Takashi T.; Yokoyama, Jun

    2015-01-01

    When pollinators use flower color to locate food sources, a distinct color can serve as a reproductive barrier against co-flowering species. This anti-interference function of flower color may result in a community assembly of plant species displaying mutually different flower colors. However, such color dispersion is not ubiquitous, suggesting a variable selection across communities and existence of some opposing factors. We conducted a 30-week study in a plant community and measured the floral reflectances of 244 species. The reflectances were evaluated in insect color spaces (bees, swallowtails, and flies), and the dispersion was compared with random expectations. We found that co-existing colors were overdispersed for each analyzed pollinator type, and this overdispersion was statistically significant for bees. Furthermore, we showed that exclusion of 32 aliens from the analysis significantly increased the color dispersion of native flowers in every color space. This result indicated that aliens disturbed a native plant–pollinator network via similarly colored flowers. Our results demonstrate the masking effects of aliens in the detection of color dispersion of native flowers and that variations in pollinator vision yield different outcomes. Our results also support the hypothesis that co-flowering species are one of the drivers of color diversification and affect the community assembly. PMID:26650121

  13. Report to the Congressional Defense Committees: Status of the Department of Defense’s Business Transformation Efforts

    DTIC Science & Technology

    2008-03-15

    information insures timely payment of entitlements and foregoes receipt of mutually exclusive payments. This depth of information supplies visibility and...reporting capability, and integration with authoritative data sources such as FPDS- NG, CCR, and contractor companies to improve data quality and reduce...manual entry requirements in Q2 FY09. • Continue to implement in theater, focusing on contingency contracts for private security companies and

  14. A Semantics of Synchronization.

    DTIC Science & Technology

    1980-09-01

    suggestion of having very hungry philosophers. One can easily imagine the complexity of the equivalent implementation using semaphores . Synchronization types...Edinburgh, July 1978. [STAR79] Stark, E.W., " Semaphore Primitives and Fair Mutual Exclusion," TM-158, Laboratory for Computer Science, M.I.T., Cambridge...AD-AQ91 015 MASSACHUSETTS INST OF TECH CAMBRIDGE LAB FOR COMPUTE--ETC F/S 9/2 A SEMANTICS OF SYNCHRONIZATION .(U) .C SEP 80 C A SEAQUIST N00015-75

  15. Genomic Variability of Mycobacterium tuberculosis Strains of the Euro-American Lineage Based on Large Sequence Deletions and 15-Locus MIRU-VNTR Polymorphism

    PubMed Central

    Rindi, Laura; Medici, Chiara; Bimbi, Nicola; Buzzigoli, Andrea; Lari, Nicoletta; Garzelli, Carlo

    2014-01-01

    A sample of 260 Mycobacterium tuberculosis strains assigned to the Euro-American family was studied to identify phylogenetically informative genomic regions of difference (RD). Mutually exclusive deletions of regions RD115, RD122, RD174, RD182, RD183, RD193, RD219, RD726 and RD761 were found in 202 strains; the RDRio deletion was detected exclusively among the RD174-deleted strains. Although certain deletions were found more frequently in certain spoligotype families (i.e., deletion RD115 in T and LAM, RD174 in LAM, RD182 in Haarlem, RD219 in T and RD726 in the “Cameroon” family), the RD-defined sublineages did not specifically match with spoligotype-defined families, thus arguing against the use of spoligotyping for establishing exact phylogenetic relationships between strains. Notably, when tested for katG463/gyrA95 polymorphism, all the RD-defined sublineages belonged to Principal Genotypic Group (PGG) 2, except sublineage RD219 exclusively belonging to PGG3; the 58 Euro-American strains with no deletion were of either PGG2 or 3. A representative sample of 197 isolates was then analyzed by standard 15-locus MIRU-VNTR typing, a suitable approach to independently assess genetic relationships among the strains. Analysis of the MIRU-VNTR typing results by using a minimum spanning tree (MST) and a classical dendrogram showed groupings that were largely concordant with those obtained by RD-based analysis. Isolates of a given RD profile show, in addition to closely related MIRU-VNTR profiles, related spoligotype profiles that can serve as a basis for better spoligotype-based classification. PMID:25197794

  16. [Mutual aid societies for industrial accidents and occupational diseases in the social security service within the framework of the Prevention of Occupational Risk Act].

    PubMed

    Albalá-Ortiz, M

    The passing of the Prevention of Industrial Risks Act, in force from 9 February 1996 has altered previous ideas on the subject, which is currently considered to be of utmost importance for national and community legislation. In this article we describe the preventive functions of the Mutual Aid Societies for Industrial Accidents and professional diseases of the National Health Service. We have analysed the current legislation so as to clarify the activities of the Mutual Aid Societies in the field of the prevention of industrial accidents, and have defined the actions which may be taken in this field according to the present laws. Two different types of preventive activities are considered: (1) Those which depend on contributions, included in the professional risks cover, and which are obliged to prepare an annual plan of the measures taken to prevent industrial accidents and professional illness, following the guidelines established by the Ministry of Labor and Social Services and according to certain priorities. (2) The functions corresponding to the services for third-party prevention exclusively for their associated companies when the Mutual Aid Society is approved as a service for third party cover. This requires a voluntary or professional contract and the financial cost is borne by the company which requests it. The objective of the current legislation is, amongst other things, to introduce the new preventive approach established by the Prevention of Industrial Risks Act in the workplace and through the Mutual Aid Societies as well as to foment a new culture of prevention.

  17. FGFR2 Point Mutations in 466 Endometrioid Endometrial Tumors: Relationship with MSI, KRAS, PIK3CA, CTNNB1 Mutations and Clinicopathological Features

    PubMed Central

    Powell, Matthew A.; Wellens, Candice L.; Gao, Feng; Mutch, David G.; Goodfellow, Paul J.; Pollock, Pamela M.

    2012-01-01

    Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35–7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09–3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05–0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies. PMID:22383975

  18. Characterization of 1,577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathological Insights into Molecular Subtypes

    PubMed Central

    Tomlins, Scott A.; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B.; Dicker, Adam P.; Trock, Bruce; DeMarzo, Angelo; Ross, Ashley; Schaeffer, Edward M.; Klein, Eric A.; Magi-Galluzzi, Cristina; Karnes, Jeffery R.; Jenkins, Robert B.; Feng, Felix Y.

    2015-01-01

    Background Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 over-expression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. Objective To determine the analytical validity and clinicopatholgical associations of microarray-based molecular subtyping. Design, Setting and Participants We analyzed Affymetrix GeneChip expression profiles for 1,577 patients from eight radical prostatectomy (RP) cohorts, including 1,351 cases assessed using the Decipher prognostic assay (performed in a CLIA-certified laboratory). A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS+) or SPINK1 over-expression (SPINK1+). Outcome Measurements Associations with clinical features and outcomes by multivariable logistic regression analysis and receiver operating curves. Results and Limitations The m-ERG classifier showed 95% accuracy in an independent validation subset (n=155 samples). Across cohorts, 45%, 9%, 8% and 38% of PCa were classified as m-ERG+, m-ETS+, m-SPINK1+, and triple negative (m-ERG−/m-ETS−/m-SPINK1−), respectively. Gene expression profiling supports three underlying molecularly defined groups (m-ERG+, m-ETS+ and m-SPINK1+/triple negative). On multivariable analysis, m-ERG+ tumors were associated with lower preoperative serum PSA and Gleason scores, but enriched for extraprostatic extension (p<0.001). m-ETS+ tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1+/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different between subtypes. Conclusions A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathological differences were found among subtypes based on global expression patterns. PMID:25964175

  19. Sugary secretions of wasp galls: a want-to-be extrafloral nectar?

    PubMed

    Aranda-Rickert, Adriana; Rothen, Carolina; Diez, Patricia; González, Ana María; Marazzi, Brigitte

    2017-11-10

    The most widespread form of protective mutualisms is represented by plants bearing extrafloral nectaries (EFNs) that attract ants and other arthropods for indirect defence. Another, but less common, form of sugary secretion for indirect defence occurs in galls induced by cynipid wasps. Until now, such galls have been reported only for cynipid wasps that infest oak trees in the northern hemisphere. This study provides the first evidence of galls that exude sugary secretions in the southern hemisphere and asks whether they can be considered as analogues of plants' EFNs. The ecology and anatomy of galls and the chemical composition of the secretion were investigated in north-western Argentina, in natural populations of the host trees Prosopis chilensis and P. flexuosa . To examine whether ants protect the galls from natural enemies, ant exclusion experiments were conducted in the field. The galls produce large amounts of sucrose-rich, nectar-like secretions. No typical nectary and sub-nectary parenchymatic tissues or secretory trichomes can be observed; instead there is a dense vascularization with phloem elements reaching the gall periphery. At least six species of ants, but also vespid wasps, Diptera and Coleoptera, consumed the gall secretions. The ant exclusion experiment showed that when ants tended galls, no differences were found in the rate of successful emergence of gall wasps or in the rate of parasitism and inquiline infestation compared with ant-excluded galls. The gall sugary secretion is not analogous to extrafloral nectar because no nectar-producing structure is associated with it, but is functionally equivalent to arthropod honeydew because it provides indirect defence to the plant parasite. As in other facultative mutualisms mediated by sugary secretions, the gall secretion triggers a complex multispecies interaction, in which the outcome of individual pair-wise interactions depends on the ecological context in which they take place. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. Enforcement of entailment constraints in distributed service-based business processes.

    PubMed

    Hummer, Waldemar; Gaubatz, Patrick; Strembeck, Mark; Zdun, Uwe; Dustdar, Schahram

    2013-11-01

    A distributed business process is executed in a distributed computing environment. The service-oriented architecture (SOA) paradigm is a popular option for the integration of software services and execution of distributed business processes. Entailment constraints, such as mutual exclusion and binding constraints, are important means to control process execution. Mutually exclusive tasks result from the division of powerful rights and responsibilities to prevent fraud and abuse. In contrast, binding constraints define that a subject who performed one task must also perform the corresponding bound task(s). We aim to provide a model-driven approach for the specification and enforcement of task-based entailment constraints in distributed service-based business processes. Based on a generic metamodel, we define a domain-specific language (DSL) that maps the different modeling-level artifacts to the implementation-level. The DSL integrates elements from role-based access control (RBAC) with the tasks that are performed in a business process. Process definitions are annotated using the DSL, and our software platform uses automated model transformations to produce executable WS-BPEL specifications which enforce the entailment constraints. We evaluate the impact of constraint enforcement on runtime performance for five selected service-based processes from existing literature. Our evaluation demonstrates that the approach correctly enforces task-based entailment constraints at runtime. The performance experiments illustrate that the runtime enforcement operates with an overhead that scales well up to the order of several ten thousand logged invocations. Using our DSL annotations, the user-defined process definition remains declarative and clean of security enforcement code. Our approach decouples the concerns of (non-technical) domain experts from technical details of entailment constraint enforcement. The developed framework integrates seamlessly with WS-BPEL and the Web services technology stack. Our prototype implementation shows the feasibility of the approach, and the evaluation points to future work and further performance optimizations.

  1. [Alternative medicine, from North America to East Asia: between persistent exclusion and embodied pluralism].

    PubMed

    Monnais, Laurence

    2017-02-01

    At a time of growing interest in integrative approaches to health and care, this article examines, from a historical perspective, the factors underlying the global popularity of so-called complementary and alternative medicines (CAM). Focusing on the multiple and changing meanings of the concepts used with reference to CAM since the nineteenth century, it emphasizes the agency of CAM practitioners' and calls into question a linear progression from outright exclusion to gradual inclusion into mainstream health care systems. This analysis concludes that biomedicine and "other" medical systems have mutually defined each other in a process of co-production that has had a significant impact on the medicalization of contemporary societies from North America to East Asia. © 2017 médecine/sciences – Inserm.

  2. Clinic and Functional Analysis of p73R1 Mutations in Prostate Cancer

    DTIC Science & Technology

    2006-02-01

    sequence variants in Marfan syndrome and related connective tissue disorders. Genet Test 1:237-42. Matsuoka S, Huang M, Elledge SJ. 1998. Linkage of ATM... Syndrome (LFS; MIM# 151623), a highly penetrant familial cancer phenotype, usually associated with inherited mutations in TP53 (Bell, et al., 1999...TP53 (Table 1). Mutually exclusive mutations of CHEK2 and TP53 have been reported in patients with Li-Fraumeni syndrome (LFS) and also in patients

  3. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

    PubMed

    Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-07-01

    Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

  4. The evolution of increased competitive ability, innate competitive advantages, and novel biochemical weapons act in concert for a tropical invader.

    PubMed

    Qin, Rui-Min; Zheng, Yu-Long; Valiente-Banuet, Alfonso; Callaway, Ragan M; Barclay, Gregor F; Pereyra, Carlos Silva; Feng, Yu-Long

    2013-02-01

    There are many non-mutually exclusive mechanisms for exotic invasions but few studies have concurrently tested more than one hypothesis for the same species. Here, we tested the evolution of increased competitive ability (EICA) hypothesis in two common garden experiments in which Chromolaena odorata plants originating from native and nonnative ranges were grown in competition with natives from each range, and the novel weapons hypothesis in laboratory experiments with leachates from C. odorata. Compared with conspecifics originating from the native range, C. odorata plants from the nonnative range were stronger competitors at high nutrient concentrations in the nonnative range in China and experienced far more herbivore damage in the native range in Mexico. In both China and Mexico, C. odorata was more suppressed by species native to Mexico than by species native to China. Species native to China were much more inhibited by leaf extracts from C. odorata than species from Mexico, and this difference in allelopathic effects may provide a possible explanation for the biogeographic differences in competitive ability. Our results indicate that EICA, innate competitive advantages, and novel biochemical weapons may act in concert to promote invasion by C. odorata, and emphasize the importance of exploring multiple, non-mutually exclusive mechanisms for invasions. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  5. Cardiovascular disease and musculoskeletal disorder labels in family practice acted as markers of physical health severity.

    PubMed

    Prior, James A; Kadam, Umesh T

    2011-05-01

    Family practitioner diagnostic labels applied in consultation provide a signpost for treatment and management. Yet, it is unknown whether each label reflects the health of the respective patient group. Consultation records of 7,799 patients aged 50 years and older from six family practices were linked to a cross-sectional baseline health survey. Associations between six mutually exclusive cardiovascular disease and nine mutually exclusive musculoskeletal disorder categories, and physical health severity as measured by the Short Form-12 questionnaire were examined. There were 2,447 (31.4%) cardiovascular disease and 3,321 (42.6%) musculoskeletal disorder consulters. The mean physical health scores ranged from 38.38 (95% confidence interval [CI]: 37.8-39.0) for hypertension to the poorest score of health 28.98 (95% CI: 27.5-30.5) for consulters with heart failure, whereas in the musculoskeletal disorder group, scores ranged from 44.85 (95% CI: 42.2-47.5) for soft tissue disorder to 28.79 (95% CI: 26.8-30.8) for consulters with inflammatory polyarthropathy (trend P<0.001). This trend in the association between diagnostic categories and physical health severity within both spectrums remained after adjustment for confounders. Specific diagnostic labels for selected chronic illness indicate the severity of physical health for the corresponding consulting population. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Infants prefer the faces of strangers or mothers to morphed faces: an uncanny valley between social novelty and familiarity.

    PubMed

    Matsuda, Yoshi-Taka; Okamoto, Yoko; Ida, Misako; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

    2012-10-23

    The 'uncanny valley' response is a phenomenon involving the elicitation of a negative feeling and subsequent avoidant behaviour in human adults and infants as a result of viewing very realistic human-like robots or computer avatars. It is hypothesized that this uncanny feeling occurs because the realistic synthetic characters elicit the concept of 'human' but fail to satisfy it. Such violations of our normal expectations regarding social signals generate a feeling of unease. This conflict-induced uncanny valley between mutually exclusive categories (human and synthetic agent) raises a new question: could an uncanny feeling be elicited by other mutually exclusive categories, such as familiarity and novelty? Given that infants prefer both familiarity and novelty in social objects, we address this question as well as the associated developmental profile. Using the morphing technique and a preferential-looking paradigm, we demonstrated uncanny valley responses of infants to faces of mothers (i.e. familiarity) and strangers (i.e. novelty). Furthermore, this effect strengthened with the infant's age. We excluded the possibility that infants detect and avoid traces of morphing. This conclusion follows from our finding that the infants equally preferred strangers' faces and the morphed faces of two strangers. These results indicate that an uncanny valley between familiarity and novelty may accentuate the categorical perception of familiar and novel objects.

  7. Diagnosis and management of differentiated thyroid cancer using molecular biology.

    PubMed

    Witt, Robert L; Ferris, Robert L; Pribitkin, Edmund A; Sherman, Steven I; Steward, David L; Nikiforov, Yuri E

    2013-04-01

    To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer. Ovid Medline 2006-2012 Manuscripts with clinical correlates. Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation. 1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

  8. Tendinopathy in diabetes mellitus patients-Epidemiology, pathogenesis, and management.

    PubMed

    Lui, P P Y

    2017-08-01

    Chronic tendinopathy is a frequent and disabling musculo-skeletal problem affecting the athletic and general populations. The affected tendon is presented with local tenderness, swelling, and pain which restrict the activity of the individual. Tendon degeneration reduces the mechanical strength and predisposes it to rupture. The pathogenic mechanisms of chronic tendinopathy are not fully understood and several major non-mutually exclusive hypotheses including activation of the hypoxia-apoptosis-pro-inflammatory cytokines cascade, neurovascular ingrowth, increased production of neuromediators, and erroneous stem cell differentiation have been proposed. Many intrinsic and extrinsic risk/causative factors can predispose to the development of tendinopathy. Among them, diabetes mellitus is an important risk/causative factor. This review aims to appraise the current literature on the epidemiology and pathology of tendinopathy in diabetic patients. Systematic reviews were done to summarize the literature on (a) the association between diabetes mellitus and tendinopathy/tendon tears, (b) the pathological changes in tendon under diabetic or hyperglycemic conditions, and (c) the effects of diabetes mellitus or hyperglycemia on the outcomes of tendon healing. The potential mechanisms of diabetes mellitus in causing and exacerbating tendinopathy with reference to the major non-mutually exclusive hypotheses of the pathogenic mechanisms of chronic tendinopathy as reported in the literature are also discussed. Potential strategies for the management of tendinopathy in diabetic patients are presented. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Introducing the Qplex: a novel arena for quantum theory

    NASA Astrophysics Data System (ADS)

    Appleby, Marcus; Fuchs, Christopher A.; Stacey, Blake C.; Zhu, Huangjun

    2017-07-01

    We reconstruct quantum theory starting from the premise that, as Asher Peres remarked, "Unperformed experiments have no results." The tools of quantum information theory, and in particular the symmetric informationally complete (SIC) measurements, provide a concise expression of how exactly Peres's dictum holds true. That expression is a constraint on how the probability distributions for outcomes of different, hypothetical and mutually exclusive experiments ought to mesh together, a type of constraint not foreseen in classical thinking. Taking this as our foundational principle, we show how to reconstruct the formalism of quantum theory in finite-dimensional Hilbert spaces. The central variety of mathematical entity in our reconstruction is the qplex, a very particular type of subset of a probability simplex. Along the way, by closely studying the symmetry properties of qplexes, we derive a condition for the existence of a d-dimensional SIC.

  10. Dual-channel in-line digital holographic double random phase encryption

    PubMed Central

    Das, Bhargab; Yelleswarapu, Chandra S; Rao, D V G L N

    2012-01-01

    We present a robust encryption method for the encoding of 2D/3D objects using digital holography and virtual optics. Using our recently developed dual-plane in-line digital holography technique, two in-line digital holograms are recorded at two different planes and are encrypted using two different double random phase encryption configurations, independently. The process of using two mutually exclusive encryption channels makes the system more robust against attacks since both the channels should be decrypted accurately in order to get a recognizable reconstruction. Results show that the reconstructed object is unrecognizable even when the portion of the correct phase keys used during decryption is close to 75%. The system is verified against blind decryptions by evaluating the SNR and MSE. Validation of the proposed method and sensitivities of the associated parameters are quantitatively analyzed and illustrated. PMID:23471012

  11. A Chinese view of the Western nursing metaparadigm.

    PubMed

    Kao, Hsueh-Fen Sabrina; Reeder, Francelyn M; Hsu, Min-Tao; Cheng, Su-Fen

    2006-06-01

    The purpose of this article is to reveal Chinese-rooted meanings present within the Western nursing metaparadigm and to illustrate some similarities with Rogers's Science of Unitary Human Beings. Confucian and Taoist beliefs have the potential to illuminate the basic constructs inherent in holistic nursing. The Western nursing metaparadigm of four concepts--person, nursing, health, and environment--was explored through the lens of a Chinese worldview and led to the presentation of a broadened view for an integrated model of nursing. Asian and Western worldviews of human beings and health are not mutually exclusive. The Chinese holistic worldview of Taoism and Confucianism resonates theoretically and cosmically with the dynamic nature of the human-environment mutual relationship basic to Rogers' unitary view. This strong, theoretical link, when elaborated for its similarities and implications, can broaden the knowledge base to guide contemporary nursing practice, education, and research, particularly relevant for holistic nursing.

  12. Accuracy and biases in newlyweds' perceptions of each other: not mutually exclusive but mutually beneficial.

    PubMed

    Luo, Shanhong; Snider, Anthony G

    2009-11-01

    There has been a long-standing debate about whether having accurate self-perceptions or holding positive illusions of self is more adaptive. This debate has recently expanded to consider the role of accuracy and bias of partner perceptions in romantic relationships. In the present study, we hypothesized that because accuracy, positivity bias, and similarity bias are likely to serve distinct functions in relationships, they should all make independent contributions to the prediction of marital satisfaction. In a sample of 288 newlywed couples, we tested this hypothesis by simultaneously modeling the actor effects and partner effects of accuracy, positivity bias, and similarity bias in predicting husbands' and wives' satisfaction. Findings across several perceptual domains suggest that all three perceptual indices independently predicted the perceiver's satisfaction. Accuracy and similarity bias, but not positivity bias, made unique contributions to the target's satisfaction. No sex differences were found.

  13. A Risk-Continuum Categorization of Product Use Among US Youth Tobacco Users.

    PubMed

    El-Toukhy, Sherine; Choi, Kelvin

    2016-07-01

    To examine prevalence and correlates of five mutually exclusive tobacco-use patterns among US youth tobacco users. A nationally representative sample of tobacco users (N = 3202, 9-17 years) was classified into five product-use patterns. Weighted multinominal and multivariate logistic regression models were used to examine prevalence of product-use patterns by gender, race and ethnicity, and grade level; and associations between product-use patterns and perceived accessibility of tobacco products, exposure and receptivity to pro-tobacco marketing, social benefits of smoking, and tobacco-associated risks. Dual use (ie, use of two product categories) was the most prevalent pattern (30.5%), followed by non-cigarette combustible only (26.7%), polytobacco (ie, use of three product categories; 17.5%), cigarette only (14.9%), and noncombustible only (10.4%) use. Product-use patterns differed by gender, race, and ethnicity. Compared to cigarette only users, dual and polytobacco users were more likely to be exposed to and be receptive to pro-tobacco marketing, and were less likely to acknowledge tobacco-use related risks (Ps < .05). Curbing tobacco use warrants research on users of more than one tobacco-product categories according to the risk-continuum categorization. We present a risk-continuum categorization of product-use patterns among tobacco users not older than 17 years. We classify tobacco users into five mutually exclusive product-use patterns: cigarette only users, non-cigarette combustible only users, noncombustible only users, dual use, and polytobacco use. This categorization overcomes limitations in current literature on tobacco-use patterns, which include exclusion of certain products (eg, e-cigarettes) and product-use patterns (eg, exclusive users of non-cigarette products), and inconsistent classification of tobacco users. It is parsimonious yet complex enough to retain differential characteristics of sub-tobacco users based on number (single, dual, polytobacco) and categories (cigarettes, non-cigarette combustibles, noncombustibles) of tobacco products consumed. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Failure to learn from feedback underlies word learning difficulties in toddlers at risk for autism.

    PubMed

    Bedford, R; Gliga, T; Frame, K; Hudry, K; Chandler, S; Johnson, M H; Charman, T

    2013-01-01

    Children's assignment of novel words to nameless objects, over objects whose names they know (mutual exclusivity; ME) has been described as a driving force for vocabulary acquisition. Despite their ability to use ME to fast-map words (Preissler & Carey, 2005), children with autism show impaired language acquisition. We aimed to address this puzzle by building on studies showing that correct referent selection using ME does not lead to word learning unless ostensive feedback is provided on the child's object choice (Horst & Samuelson, 2008). We found that although toddlers aged 2;0 at risk for autism can use ME to choose the correct referent of a word, they do not benefit from feedback for long-term retention of the word-object mapping. Further, their difficulty using feedback is associated with their smaller receptive vocabularies. We propose that difficulties learning from social feedback, not lexical principles, limits vocabulary building during development in children at risk for autism.

  15. Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

    PubMed

    Takeda, Kenichi; Yamasaki, Akira; Igishi, Tadashi; Kawasaki, Yuji; Ito-Nishii, Shizuka; Izumi, Hiroki; Sakamoto, Tomohiro; Touge, Hirokazu; Kodani, Masahiro; Makino, Haruhiko; Yanai, Masaaki; Tanaka, Natsumi; Matsumoto, Shingo; Araki, Kunio; Nakamura, Hiroshige; Shimizu, Eiji

    2017-02-01

    Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed. All patients were categorized into the emphysema or non-emphysema group. Wild-type EGFR was detected in 136 (54%) and mutant EGFR in 48 (19%). Emphysematous changes were observed in 87 (36%) patients. EGFR mutation was highly frequent in the non-emphysema group (p=0.0014). Multivariate logistic regression analysis showed that emphysema was an independent risk factor for reduced frequency of EGFR mutation (Odds Ratio=3.47, p=0.005). Our data showed a relationship between emphysematous changes and EGFR mutation status. There might be mutually exclusive genetic risk factors for carcinogenesis and development of emphysematous changes. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

    PubMed

    Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Horswell, Stuart; Chambers, Tim; O'Brien, Tim; Lopez, Jose I; Watkins, Thomas B K; Nicol, David; Stares, Mark; Challacombe, Ben; Hazell, Steve; Chandra, Ashish; Mitchell, Thomas J; Au, Lewis; Eichler-Jonsson, Claudia; Jabbar, Faiz; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Stewart, Aengus; Xing, Wei; Smith, Jonathan C; Escudero, Mickael; Huffman, Adam; Matthews, Nik; Elgar, Greg; Phillimore, Ben; Costa, Marta; Begum, Sharmin; Ward, Sophia; Salm, Max; Boeing, Stefan; Fisher, Rosalie; Spain, Lavinia; Navas, Carolina; Grönroos, Eva; Hobor, Sebastijan; Sharma, Sarkhara; Aurangzeb, Ismaeel; Lall, Sharanpreet; Polson, Alexander; Varia, Mary; Horsfield, Catherine; Fotiadis, Nicos; Pickering, Lisa; Schwarz, Roland F; Silva, Bruno; Herrero, Javier; Luscombe, Nick M; Jamal-Hanjani, Mariam; Rosenthal, Rachel; Birkbak, Nicolai J; Wilson, Gareth A; Pipek, Orsolya; Ribli, Dezso; Krzystanek, Marcin; Csabai, Istvan; Szallasi, Zoltan; Gore, Martin; McGranahan, Nicholas; Van Loo, Peter; Campbell, Peter; Larkin, James; Swanton, Charles

    2018-04-19

    The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

  17. Ant-plant mutualism: a dietary by-product of a tropical ant's macronutrient requirements.

    PubMed

    Arcila Hernández, Lina M; Sanders, Jon G; Miller, Gabriel A; Ravenscraft, Alison; Frederickson, Megan E

    2017-12-01

    Many arboreal ants depend on myrmecophytic plants for both food and shelter; in return, these ants defend their host plants against herbivores, which are often insects. Ant-plant and other mutualisms do not necessarily involve the exchange of costly rewards or services; they may instead result from by-product benefits, or positive outcomes that do not entail a cost for one or both partners. Here, we examined whether the plant-ant Allomerus octoarticulatus pays a short-term cost to defend their host plants against herbivores, or whether plant defense is a by-product benefit of ant foraging for insect prey. Because the food offered by ant-plants is usually nitrogen-poor, arboreal ants may balance their diets by consuming insect prey or associating with microbial symbionts to acquire nitrogen, potentially shifting the costs and benefits of plant defense for the ant partner. To determine the effect of ant diet on an ant-plant mutualism, we compared the behavior, morphology, fitness, stable isotope signatures, and gaster microbiomes of A. octoarticulatus ants nesting in Cordia nodosa trees maintained for nearly a year with or without insect herbivores. At the end of the experiment, ants from herbivore exclosures preferred protein-rich baits more than ants in the control (i.e., herbivores present) treatment. Furthermore, workers in the control treatment were heavier than in the herbivore-exclusion treatment, and worker mass predicted reproductive output, suggesting that foraging for insect prey directly increased ant colony fitness. The gaster microbiome of ants was not significantly affected by the herbivore exclusion treatment. We conclude that the defensive behavior of some phytoecious ants is a by-product of their need for external protein sources; thus, the consumption of insect herbivores by ants benefits both the ant colony and the host plant. © 2017 by the Ecological Society of America.

  18. Mother- and father-child mutuality in Anglo and Indian British families: a link with lower externalizing problems.

    PubMed

    Deater-Deckard, Kirby; Atzaba-Poria, Naama; Pike, Alison

    2004-12-01

    We observed mother- and father-child dyadic mutuality (responsiveness, interaction reciprocity, and cooperation), and its association with child behavior problems, in a socioeconomically and ethnically diverse sample of 125 male (51%) and female 7-to-9-year-old children. Dyadic mutuality and positivity were coded from in-home videotaped structured tasks, and parents completed ratings of child externalizing problems. Mothers showed more mutuality than fathers. The same child showed moderately similar mutuality with both of her or his parents (r = .47). Mutuality was higher among Anglo parents compared to Indian parents, an effect that was due in part to acculturation (i.e., years since immigration, native language use, traditional native culture attitudes). Greater mutuality, when coupled with dyadic positive affect, was associated with fewer externalizing problems (R2 = .24). This pattern held across gender, ethnic, and sociocconomic groups.

  19. Hypersonic Combined Cycle Propulsion Panel Symposium (75th) Held in Madrid, Spain on 28 May - 1 June 1990 (La Propulsion Hypersonique a Cycles Combines)

    DTIC Science & Technology

    1990-12-01

    mutually exclusive. That is, they may be utilized simultaneously to compound the additive refrigerative enhancement effect. The Recycled ScramLACE (Figure...small positive reaction (say 10%) in order to obviate diffusion. Impulse stages can be velocity compounded , an arrangement in which a large pressure...with more effective seals. Conceptually, it is possible to design a series of velocity compounded stages to run in tandem to give the correct overall

  20. Induction of belief decision trees from data

    NASA Astrophysics Data System (ADS)

    AbuDahab, Khalil; Xu, Dong-ling; Keane, John

    2012-09-01

    In this paper, a method for acquiring belief rule-bases by inductive inference from data is described and evaluated. Existing methods extract traditional rules inductively from data, with consequents that are believed to be either 100% true or 100% false. Belief rules can capture uncertain or incomplete knowledge using uncertain belief degrees in consequents. Instead of using singled-value consequents, each belief rule deals with a set of collectively exhaustive and mutually exclusive consequents. The proposed method extracts belief rules from data which contain uncertain or incomplete knowledge.

  1. A Minimum-Residual Finite Element Method for the Convection-Diffusion Equation

    DTIC Science & Technology

    2013-05-01

    4p . We note that these two choices of discretization for V are not mutually exclusive, and that novel choices for Vh are likely the key to yielding...the inside with the positive- definite operator A, which is precisely the discrete system that arises under the optimal test function framework of DPG...converts the fine-scale problem into a symmetric-positive definite one, allowing for a well-behaved subgrid model of fine scale behavior. We begin again

  2. Bioethical pluralism and complementarity.

    PubMed

    Grinnell, Frederick; Bishop, Jeffrey P; McCullough, Laurence B

    2002-01-01

    This essay presents complementarity as a novel feature of bioethical pluralism. First introduced by Neils Bohr in conjunction with quantum physics, complementarity in bioethics occurs when different perspectives account for equally important features of a situation but are mutually exclusive. Unlike conventional approaches to bioethical pluralism, which attempt in one fashion or another to isolate and choose between different perspectives, complementarity accepts all perspectives. As a result, complementarity results in a state of holistic, dynamic tension, rather than one that yields singular or final moral judgments.

  3. Omega System Performance Assessment

    DTIC Science & Technology

    1989-03-01

    defined locally (i.e., a point 3-9 function of space and time), a weighted average of P(X 3) over the earth’s surface is taken to match the definition...operations which follow, product indicates set intersection and addition indicates set union . 3-10 Bi event that only station i is off-air, i = 1, 2...case, event X3 could not occur under any circumstances. By expressing the set universe as the union of all possible (mutually exclusive) B-events, it is

  4. Idealism and materialism in perception.

    PubMed

    Rose, David; Brown, Dora

    2015-01-01

    Koenderink (2014, Perception, 43, 1-6) has said most Perception readers are deluded, because they believe an 'All Seeing Eye' observes an objective reality. We trace the source of Koenderink's assertion to his metaphysical idealism, and point to two major weaknesses in his position-namely, its dualism and foundationalism. We counter with arguments from modern philosophy of science for the existence of an objective material reality, contrast Koenderink's enactivism to his idealism, and point to ways in which phenomenology and cognitive science are complementary and not mutually exclusive.

  5. Characterizing genomic alterations in cancer by complementary functional associations | Office of Cancer Genomics

    Cancer.gov

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment.

  6. Reinstatement in a Cocaine vs. Food Choice Situation: Reversal of Preference between Drug and Non-Drug Rewards

    PubMed Central

    Tunstall, Brendan J.; Kearns, David N.

    2013-01-01

    Recent studies (for review see Ahmed, 2010; 2012) show that when given a mutually exclusive choice between cocaine and food, rats almost exclusively choose food. The present experiment investigated potential shifts in preference between levers associated with either food or cocaine which might occur during extinction (food and cocaine no longer available) and during footshock-induced, cocaine-primed, and food-primed reinstatement. During self-administration sessions where food and cocaine were simultaneously available, rats demonstrated a stable food preference, choosing food over cocaine on 83% of trials. During extinction when neither reinforcer was available, no preference between levers was evident and responding decreased until rats responded on the previously food- and cocaine-associated levers at equally low rates. Footshock resulted in a non-specific reinstatement of responding upon both levers, while cocaine priming resulted in a significant preference for cocaine seeking over food seeking. This suggests that the mechanism underlying footshock-induced reinstatement is distinct from that of cocaine-primed reinstatement. Food priming engendered a mild, non-specific increase in responding on both levers. Although rats generally prefer food over cocaine when presented with a choice between these primary reinforcers, the present results suggest that in certain situations cocaine-seeking behavior prevails over food-seeking behavior. PMID:23551949

  7. The GDNF Target Vsnl1 Marks the Ureteric Tip

    PubMed Central

    Ola, Roxana; Jakobson, Madis; Kvist, Jouni; Perälä, Nina; Kuure, Satu; Braunewell, Karl-Heinz; Bridgewater, Darren; Rosenblum, Norman D.; Chilov, Dmitri; Immonen, Tiina; Sainio, Kirsi

    2011-01-01

    Glial cell line-derived neurotrophic factor (GDNF) is indispensable for ureteric budding and branching. If applied exogenously, GDNF promotes ectopic ureteric buds from the Wolffian duct. Although several downstream effectors of GDNF are known, the identification of early response genes is incomplete. Here, microarray screening detected several GDNF-regulated genes in the Wolffian duct, including Visinin like 1 (Vsnl1), which encodes a neuronal calcium-sensor protein. We observed renal Vsnl1 expression exclusively in the ureteric epithelium, but not in Gdnf-null kidneys. In the tissue culture of Gdnf-deficient kidney primordium, exogenous GDNF and alternative bud inducers (FGF7 and follistatin) restored Vsnl1 expression. Hence, Vsnl1 characterizes the tip of the ureteric bud epithelium regardless of the inducer. In the tips, Vsnl1 showed a mosaic expression pattern that was mutually exclusive with β-catenin transcriptional activation. Vsnl1 was downregulated in both β-catenin-stabilized and β-catenin-deficient kidneys. Moreover, in a mouse collecting duct cell line, Vsnl1 compromised β-catenin stability, suggesting a counteracting relationship between Vsnl1 and β-catenin. In summary, Vsnl1 marks ureteric bud tips in embryonic kidneys, and its mosaic pattern demonstrates a heterogeneity of cell types that may be critical for normal ureteric branching. PMID:21289216

  8. Tackling community concerns about commercialisation and genetic research: a modest interdisciplinary proposal.

    PubMed

    Haddow, Gillian; Laurie, Graeme; Cunningham-Burley, Sarah; Hunter, Kathryn G

    2007-01-01

    In recent years, there has been a rise in the creation of DNA databases promising a range of health benefits to individuals and populations. This development has been accompanied by an interest in, and concern for the ethical, legal and social aspects of such collections. In terms of policy solutions, much of the focus of these debates has been on issues of consent, confidentiality and research governance. However, there are broader concerns, such as those associated with commercialisation, which cannot be adequately addressed by these foci. In this article, we focus on the health-wealth benefits that DNA databases promise by considering the views of 10 focus groups on Generation Scotland, Scotland's first national genetic database. As in previous studies, our qualitative research on public/s and stakeholders' views of DNA databases show the prospect of utilising donated samples and information derived for wealth-related ends (i.e. for private profit), irrespective of whether there is an associated health-related benefit, arouses considerable reaction. While health-wealth benefits are not mutually exclusive ideals, the tendency has been to cast 'public' benefits as exclusively health-related, while 'private' commercial benefits for funders and/or researchers are held out as a necessary pay-off. We argue for a less polarised approach that reconsiders what is meant by 'public benefits' and questions the exclusivity of commercial interests. We believe accommodation can be achieved via the mobilisation of a grass roots solution known as 'benefit-sharing' or a 'profit pay-off'. We propose a sociologically informed model that has a pragmatic, legal framework, which responds seriously to public concerns.

  9. Independent, specialized invasions of ectomycorrhizal mutualism by two nonphotosynthetic orchids

    PubMed Central

    Taylor, D. Lee; Bruns, Thomas D.

    1997-01-01

    We have investigated the mycorrhizal associations of two nonphotosynthetic orchids from distant tribes within the Orchidaceae. The two orchids were found to associate exclusively with two distinct clades of ectomycorrhizal basidiomycetous fungi over wide geographic ranges. Yet both orchids retained the internal mycorrhizal structure typical of photosynthetic orchids that do not associate with ectomycorrhizal fungi. Restriction fragment length polymorphism and sequence analysis of two ribosomal regions along with fungal isolation provided congruent, independent evidence for the identities of the fungal symbionts. All 14 fungal entities that were associated with the orchid Cephalanthera austinae belonged to a clade within the Thelephoraceae, and all 18 fungal entities that were associated with the orchid Corallorhiza maculata fell within the Russulaceae. Restriction fragment length polymorphism and single-strand conformational polymorphism analysis of ectomycorrhizal tree roots collected adjacent to Cephalanthera showed that (i) the fungi associated internally with Cephalanthera also form typical external ectomycorrhizae and that (ii) ectomycorrhizae formed by other Basidiomycetes were abundant where the orchid grows but these fungi did not associate with the orchid. This is the first proof of ectomycorrhizal epiparasitism in nature by an orchid. We argue that these orchids are cheaters because they do not provide fixed carbon to associated fungi. This view suggests that mycorrhizae, like other ancient mutualisms, are susceptible to cheating. The extreme specificity in these orchids relative to other ectomycorrhizal plants agrees with trends seen in more conventional parasites. PMID:9114020

  10. Assessing Vocal Development in Infants and Toddlers

    PubMed Central

    Nathani, Suneeti; Ertmer, David J.

    2012-01-01

    The purpose of this study was to examine changes in prelinguistic vocal productions during the first 20 months of life. Vocalizations were classified into 23 mutually exclusive and exhaustive types, and grouped into five ascending levels using the Stark Assessment of Early Vocal Development-Revised (SAEVD-R). Data from 30 typically developing infants, aged 0–20 months, show that older infants attained higher developmental levels on the SAEVD-R than younger infants. Infants 0–2, 3–5, and 6–8 months of age primarily produced vocalizations from Levels 1 (Reflexive), 2 (Control of Phonation), and 3 (Expansion). Infants 9–20 months of age also produced vocalizations from Level 4 (Basic Canonical Syllables). Only infants from 16–20 months of age produced Level 5 (Advanced Forms) vocalizations in significant quantities. The outcomes indicate that the SAEVD-R is a valuable instrument for evaluating prelinguistic vocal development. PMID:16728333

  11. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

    PubMed

    Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

    2014-06-16

    Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Classifying individuals based on a densely captured sequence of vital signs: An example using repeated blood pressure measurements during hemodialysis treatment.

    PubMed

    Goldstein, Benjamin A; Chang, Tara I; Winkelmayer, Wolfgang C

    2015-10-01

    Electronic Health Records (EHRs) present the opportunity to observe serial measurements on patients. While potentially informative, analyzing these data can be challenging. In this work we present a means to classify individuals based on a series of measurements collected by an EHR. Using patients undergoing hemodialysis, we categorized people based on their intradialytic blood pressure. Our primary criteria were that the classifications were time dependent and independent of other subjects. We fit a curve of intradialytic blood pressure using regression splines and then calculated first and second derivatives to come up with four mutually exclusive classifications at different time points. We show that these classifications relate to near term risk of cardiac events and are moderately stable over a succeeding two-week period. This work has general application for analyzing dense EHR data. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Reconstruction of stochastic temporal networks through diffusive arrival times

    NASA Astrophysics Data System (ADS)

    Li, Xun; Li, Xiang

    2017-06-01

    Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications.

  14. A scaling law for random walks on networks

    PubMed Central

    Perkins, Theodore J.; Foxall, Eric; Glass, Leon; Edwards, Roderick

    2014-01-01

    The dynamics of many natural and artificial systems are well described as random walks on a network: the stochastic behaviour of molecules, traffic patterns on the internet, fluctuations in stock prices and so on. The vast literature on random walks provides many tools for computing properties such as steady-state probabilities or expected hitting times. Previously, however, there has been no general theory describing the distribution of possible paths followed by a random walk. Here, we show that for any random walk on a finite network, there are precisely three mutually exclusive possibilities for the form of the path distribution: finite, stretched exponential and power law. The form of the distribution depends only on the structure of the network, while the stepping probabilities control the parameters of the distribution. We use our theory to explain path distributions in domains such as sports, music, nonlinear dynamics and stochastic chemical kinetics. PMID:25311870

  15. A novel resource-service mutualism between bats and pitcher plants.

    PubMed

    Grafe, T Ulmar; Schöner, Caroline R; Kerth, Gerald; Junaidi, Anissa; Schöner, Michael G

    2011-06-23

    Mutualistic relationships between vertebrates and plants apart from the pollen and seed-dispersal syndromes are rare. At first view, carnivorous pitcher plants of the genus Nepenthes seem to be highly unlikely candidates for mutualistic interactions with animals, as they form dimorphic terrestrial and aerial pitchers that trap arthropods and small vertebrates. Surprisingly, however, the aerial pitchers of Nepenthes rafflesiana variety elongata are poor insect traps, with low amounts of insect-attractive volatile compounds and low amounts of digestive fluid. Here, we show that N. rafflesiana elongata gains an estimated 33.8 per cent of the total foliar nitrogen from the faeces of Hardwicke's woolly bats (Kerivoula hardwickii hardwickii) that exclusively roost in its aerial pitchers. This is the first case in which the faeces-trapping syndrome has been documented in a pitcher plant that attracts bats and only the second case of a mutualistic association between a carnivorous plant and a mammal to date.

  16. Adolescents, parents, and peers: what is one with or without the other?

    PubMed

    Valiant, G L

    1983-06-01

    The present study investigates the relationship between Asian and white adolescents, resident in Britain, and their parents and peers. Ninety Asian and 81 white youths aged between 11 and 16 years, completed questionnaires concerning the quality of relations with parents; conflict between parents and peers; and willingness to approach parents, peers, siblings, teachers, and religious leaders in particular situations. In addition, diaries of time spent with peers were kept for a one week period. The data tend to show that relations among youths and groups of would-be advisers are influenced by both age and cultural background. Also, they would further support the view that relations with parents and peers do not represent mutually exclusive domains, but must be seen as developing from both a consideration of the appropriateness of each group in particular circumstances as well as the availability of other groups of "significant" persons.

  17. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

    PubMed Central

    Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

  18. Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia.

    PubMed

    Wang, Jiguang; Khiabanian, Hossein; Rossi, Davide; Fabbri, Giulia; Gattei, Valter; Forconi, Francesco; Laurenti, Luca; Marasca, Roberto; Del Poeta, Giovanni; Foà, Robin; Pasqualucci, Laura; Gaidano, Gianluca; Rabadan, Raul

    2014-12-11

    Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination, and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

  19. CHIP as a membrane-shuttling proteostasis sensor

    PubMed Central

    Kopp, Yannick; Martínez-Limón, Adrián; Hofbauer, Harald F; Ernst, Robert; Calloni, Giulia

    2017-01-01

    Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function. We reconstituted this process in vitro and found that mainly phosphatidic acid and phosphatidylinositol-4-phosphate enhance association of chaperone-free CHIP with liposomes. HSP70 and membranes compete for mutually exclusive binding to the tetratricopeptide repeat domain of CHIP. At new cellular locations, access to compartment-specific substrates would enable CHIP to participate in the reorganization of the respective organelles, as exemplified by the fragmentation of the Golgi apparatus (effector function). PMID:29091030

  20. Reconstruction of stochastic temporal networks through diffusive arrival times

    PubMed Central

    Li, Xun; Li, Xiang

    2017-01-01

    Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications. PMID:28604687

  1. A scaling law for random walks on networks

    NASA Astrophysics Data System (ADS)

    Perkins, Theodore J.; Foxall, Eric; Glass, Leon; Edwards, Roderick

    2014-10-01

    The dynamics of many natural and artificial systems are well described as random walks on a network: the stochastic behaviour of molecules, traffic patterns on the internet, fluctuations in stock prices and so on. The vast literature on random walks provides many tools for computing properties such as steady-state probabilities or expected hitting times. Previously, however, there has been no general theory describing the distribution of possible paths followed by a random walk. Here, we show that for any random walk on a finite network, there are precisely three mutually exclusive possibilities for the form of the path distribution: finite, stretched exponential and power law. The form of the distribution depends only on the structure of the network, while the stepping probabilities control the parameters of the distribution. We use our theory to explain path distributions in domains such as sports, music, nonlinear dynamics and stochastic chemical kinetics.

  2. Population structuring of multi-copy, antigen-encoding genes in Plasmodium falciparum

    PubMed Central

    Artzy-Randrup, Yael; Rorick, Mary M; Day, Karen; Chen, Donald; Dobson, Andrew P; Pascual, Mercedes

    2012-01-01

    The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity. DOI: http://dx.doi.org/10.7554/eLife.00093.001 PMID:23251784

  3. Trace element evidence for a laterally inhomogeneous moon

    NASA Technical Reports Server (NTRS)

    Jovanovic, S.; Reed, G. W., Jr.

    1978-01-01

    A number of trace element interrelationships support the concept of a laterally inhomogeneous moon based originally on Clr/P2O5 ratios. The correspondence between Clr/P2O3 and Rb/Sr ratios in basalts are of special interest since the isotropic evolution of the latter pair of elements relates to the earliest history of the moon. This implies the times when the Clr/P2O5 relationships were established. The early magma ocean is conjectured to have been made up of non-intermixing seas resulting either from large convection cells or large body accretion. These mutually exclusive regions could be lunar geological provinces. It is proposed that the diversity of basalts from the Apollo 17 site is related to the lateral inhomogeneity of the moon. Ca/Na ratios in basalts show a trend which parallels that of Ru/Os and in a corresponding fashion may serve as a depth indicator.

  4. A scaling law for random walks on networks.

    PubMed

    Perkins, Theodore J; Foxall, Eric; Glass, Leon; Edwards, Roderick

    2014-10-14

    The dynamics of many natural and artificial systems are well described as random walks on a network: the stochastic behaviour of molecules, traffic patterns on the internet, fluctuations in stock prices and so on. The vast literature on random walks provides many tools for computing properties such as steady-state probabilities or expected hitting times. Previously, however, there has been no general theory describing the distribution of possible paths followed by a random walk. Here, we show that for any random walk on a finite network, there are precisely three mutually exclusive possibilities for the form of the path distribution: finite, stretched exponential and power law. The form of the distribution depends only on the structure of the network, while the stepping probabilities control the parameters of the distribution. We use our theory to explain path distributions in domains such as sports, music, nonlinear dynamics and stochastic chemical kinetics.

  5. The influence of hold time on the onset of plastic deformation in silicon

    DOE PAGES

    Wong, Sherman; Haberl, Bianca; Bradby, Jodie E.; ...

    2015-12-24

    Here, the formation of silicon (Si) in its -Sn form is known to be nucleation limited, with an undetermined period of time between when critical pressure for the trans- formation is reached and when the transformation actually occurs. In this letter, we use nanoindentation to apply critical pressure to diamond cubic Si and hold the sample under pressure to promote deformation via phase transformation and crystalline defects. We report that the number of indents in which phase transformation is observed increases with increasing hold time. Interestingly, the number of indents in which crystalline defects are observed also increase with increasingmore » hold time, suggesting crystalline defects are also nucleation limited. Raman spectroscopy and cross-sectional transmission electron microscopy is used to show that these two deformation mechanisms are mutually exclusive under the indentation conditions used within this letter.« less

  6. Constraints for the thawing and freezing potentials

    NASA Astrophysics Data System (ADS)

    Hara, Tetsuya; Suzuki, Anna; Saka, Shogo; Tanigawa, Takuma

    2018-01-01

    We study the accelerating present universe in terms of the time evolution of the equation of state w(z) (redshift z) due to thawing and freezing scalar potentials in the quintessence model. The values of dw/da and d^2w/da^2 at a scale factor of a = 1 are associated with two parameters of each potential. For five types of scalar potentials, the scalar fields Q and w as functions of time t and/or z are numerically calculated under the fixed boundary condition of w(z=0)=-1+Δ. The observational constraint w_obs (Planck Collaboration, arXiv:1502.01590) is imposed to test whether the numerical w(z) is in w_obs. Some solutions show thawing features in the freezing potentials. Mutually exclusive allowed regions in the dw/da vs. d^2w/da^2 diagram are obtained in order to identify the likely scalar potential and even the potential parameters for future observational tests.

  7. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas

    NASA Astrophysics Data System (ADS)

    Wiesner, Thomas; He, Jie; Yelensky, Roman; Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S.; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T.; Stephens, Philip J.; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumours with distinctive histopathological features. They include benign tumours (Spitz naevi), malignant tumours (spitzoid melanomas) and tumours with borderline histopathological features and uncertain clinical outcome (atypical Spitz tumours). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbour kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%) and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signalling pathways, are tumourigenic and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz naevi, 56% of atypical Spitz tumours and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signalling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanomas.

  8. Entropic uncertainty relations and locking: Tight bounds for mutually unbiased bases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ballester, Manuel A.; Wehner, Stephanie

    We prove tight entropic uncertainty relations for a large number of mutually unbiased measurements. In particular, we show that a bound derived from the result by Maassen and Uffink [Phys. Rev. Lett. 60, 1103 (1988)] for two such measurements can in fact be tight for up to {radical}(d) measurements in mutually unbiased bases. We then show that using more mutually unbiased bases does not always lead to a better locking effect. We prove that the optimal bound for the accessible information using up to {radical}(d) specific mutually unbiased bases is log d/2, which is the same as can be achievedmore » by using only two bases. Our result indicates that merely using mutually unbiased bases is not sufficient to achieve a strong locking effect and we need to look for additional properties.« less

  9. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma

    PubMed Central

    Verma, Sonal; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-01-01

    Introduction Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. Aim To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Materials and Methods Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Results Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. Conclusion EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients. PMID:28892905

  10. Surmounting the Tower of Babel: Monolingual and bilingual 2-year-olds' understanding of the nature of foreign language words.

    PubMed

    Byers-Heinlein, Krista; Chen, Ke Heng; Xu, Fei

    2014-03-01

    Languages function as independent and distinct conventional systems, and so each language uses different words to label the same objects. This study investigated whether 2-year-old children recognize that speakers of their native language and speakers of a foreign language do not share the same knowledge. Two groups of children unfamiliar with Mandarin were tested: monolingual English-learning children (n=24) and bilingual children learning English and another language (n=24). An English speaker taught children the novel label fep. On English mutual exclusivity trials, the speaker asked for the referent of a novel label (wug) in the presence of the fep and a novel object. Both monolingual and bilingual children disambiguated the reference of the novel word using a mutual exclusivity strategy, choosing the novel object rather than the fep. On similar trials with a Mandarin speaker, children were asked to find the referent of a novel Mandarin label kuò. Monolinguals again chose the novel object rather than the object with the English label fep, even though the Mandarin speaker had no access to conventional English words. Bilinguals did not respond systematically to the Mandarin speaker, suggesting that they had enhanced understanding of the Mandarin speaker's ignorance of English words. The results indicate that monolingual children initially expect words to be conventionally shared across all speakers-native and foreign. Early bilingual experience facilitates children's discovery of the nature of foreign language words. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. MFIB: a repository of protein complexes with mutual folding induced by binding.

    PubMed

    Fichó, Erzsébet; Reményi, István; Simon, István; Mészáros, Bálint

    2017-11-15

    It is commonplace that intrinsically disordered proteins (IDPs) are involved in crucial interactions in the living cell. However, the study of protein complexes formed exclusively by IDPs is hindered by the lack of data and such analyses remain sporadic. Systematic studies benefited other types of protein-protein interactions paving a way from basic science to therapeutics; yet these efforts require reliable datasets that are currently lacking for synergistically folding complexes of IDPs. Here we present the Mutual Folding Induced by Binding (MFIB) database, the first systematic collection of complexes formed exclusively by IDPs. MFIB contains an order of magnitude more data than any dataset used in corresponding studies and offers a wide coverage of known IDP complexes in terms of flexibility, oligomeric composition and protein function from all domains of life. The included complexes are grouped using a hierarchical classification and are complemented with structural and functional annotations. MFIB is backed by a firm development team and infrastructure, and together with possible future community collaboration it will provide the cornerstone for structural and functional studies of IDP complexes. MFIB is freely accessible at http://mfib.enzim.ttk.mta.hu/. The MFIB application is hosted by Apache web server and was implemented in PHP. To enrich querying features and to enhance backend performance a MySQL database was also created. simon.istvan@ttk.mta.hu, meszaros.balint@ttk.mta.hu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

  12. Design, Implementation, and Verification of the Reliable Multicast Protocol. Thesis

    NASA Technical Reports Server (NTRS)

    Montgomery, Todd L.

    1995-01-01

    This document describes the Reliable Multicast Protocol (RMP) design, first implementation, and formal verification. RMP provides a totally ordered, reliable, atomic multicast service on top of an unreliable multicast datagram service. RMP is fully and symmetrically distributed so that no site bears an undue portion of the communications load. RMP provides a wide range of guarantees, from unreliable delivery to totally ordered delivery, to K-resilient, majority resilient, and totally resilient atomic delivery. These guarantees are selectable on a per message basis. RMP provides many communication options, including virtual synchrony, a publisher/subscriber model of message delivery, a client/server model of delivery, mutually exclusive handlers for messages, and mutually exclusive locks. It has been commonly believed that total ordering of messages can only be achieved at great performance expense. RMP discounts this. The first implementation of RMP has been shown to provide high throughput performance on Local Area Networks (LAN). For two or more destinations a single LAN, RMP provides higher throughput than any other protocol that does not use multicast or broadcast technology. The design, implementation, and verification activities of RMP have occurred concurrently. This has allowed the verification to maintain a high fidelity between design model, implementation model, and the verification model. The restrictions of implementation have influenced the design earlier than in normal sequential approaches. The protocol as a whole has matured smoother by the inclusion of several different perspectives into the product development.

  13. Prevalence and sociodemographic determinants of tobacco use in four countries of the World Health Organization: South-East Asia region: findings from the Global Adult Tobacco Survey.

    PubMed

    Palipudi, K; Rizwan, S A; Sinha, D N; Andes, L J; Amarchand, R; Krishnan, A; Asma, S

    2014-12-01

    Tobacco use is a leading cause of deaths and Disability Adjusted Life Years lost worldwide, particularly in South-East Asia. Health risks associated with exclusive use of one form of tobacco alone has a different health risk profile when compared to dual use. In order to tease out specific profiles of mutually exclusive categories of tobacco use, we carried out this analysis. The Global Adult Tobacco Survey (GATS) data was used to describe the profiles of three mutually exclusive tobacco use categories ("Current smoking only," "Current smokeless tobacco [SLT] use only," and "Dual use") in four World Health Organization South-East Asia Region countries, namely Bangladesh, India, Indonesia and Thailand. GATS was a nationally representative household-based survey that used a stratified multistage cluster sampling design proportional to population size. Prevalence of different forms of usage were described as proportions. Logistics regression analyses was performed to calculate odds ratios (OR) with 95% confidence intervals. All analyses were weighted, accounted for the complex sampling design and conducted using SPSS version 18. The prevalence of different forms of tobacco use varied across countries. Current tobacco use ranged from 27.2% in Thailand to 43.3% in Bangladesh. Exclusively smoking was more common in Indonesia (34.0%) and Thailand (23.4%) and less common in Bangladesh (16.1%) and India (8.7%). Exclusively using SLT was more common in Bangladesh (20.3%) and India (20.6%) and less common on Indonesia (0.9%) and Thailand (3.5%). Dual use of smoking and SLT was found in Bangladesh (6.8%) and India (5.3%), but was negligible in Indonesia (0.8) and Thailand (0.4%). Gender, age, education and wealth had significant effects on the OR for most forms of tobacco use across all four countries with the exceptions of SLT use in Indonesia and dual use in both Indonesia and Thailand. In general, the different forms of tobacco use increased among males and with increasing age; and decreased with higher education and wealth. The results for urban versus rural residence were mixed and frequently not significant once controlling for the other demographic factors. This study addressed the socioeconomic disparities, which underlie health inequities due to tobacco use. Tobacco control activities in these countries should take in account local cultural, social and demographic factors for successful implementation.

  14. Memory Retrieval Has a Dynamic Influence on the Maintenance Mechanisms That Are Sensitive to ζ-Inhibitory Peptide (ZIP).

    PubMed

    Levitan, David; Fortis-Santiago, Yaihara; Figueroa, Joshua A; Reid, Emily E; Yoshida, Takashi; Barry, Nicholas C; Russo, Abigail; Katz, Donald B

    2016-10-12

    In neuroscientists' attempts to understand the long-term storage of memory, topics of particular importance and interest are the cellular and system mechanisms of maintenance (e.g., those sensitive to ζ-inhibitory peptide, ZIP) and those induced by memory retrieval (i.e., reconsolidation). Much is known about each of these processes in isolation, but less is known concerning how they interact. It is known that ZIP sensitivity and memory retrieval share at least some molecular targets (e.g., recycling α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA, receptors to the plasma membrane); conversely, the fact that sensitivity to ZIP emerges only after consolidation ends suggests that consolidation (and by extension reconsolidation) and maintenance might be mutually exclusive processes, the onset of one canceling the other. Here, we use conditioned taste aversion (CTA) in rats, a cortically dependent learning paradigm, to test this hypothesis. First, we demonstrate that ZIP infusions into gustatory cortex begin interfering with CTA memory 43-45 h after memory acquisition-after consolidation ends. Next, we show that a retrieval trial administered after this time point interrupts the ability of ZIP to induce amnesia and that ZIP's ability to induce amnesia is reengaged only 45 h after retrieval. This pattern of results suggests that memory retrieval and ZIP-sensitive maintenance mechanisms are mutually exclusive and that the progression from one to the other are similar after acquisition and retrieval. They also reveal concrete differences between ZIP-sensitive mechanisms induced by acquisition and retrieval: the latency with which ZIP-sensitive mechanisms are expressed differ for the two processes. Memory retrieval and the molecular mechanisms that are sensitive to ζ-inhibitory peptide (ZIP) are the few manipulations that have been shown to effect memory maintenance. Although much is known about their effect on maintenance separately, it is unknown how they interact. Here, we describe a model for the interaction between memory retrieval and ZIP-sensitive mechanisms, showing that retrieval trials briefly (i.e., for 45 h) interrupt these mechanisms. ZIP sensitivity emerges across a similar time window after memory acquisition and retrieval; the maintenance mechanisms that follow acquisition and retrieval differ, however, in the latency with which the impact of ZIP is expressed. Copyright © 2016 the authors 0270-6474/16/3610654-09$15.00/0.

  15. The proportional lack of archaeal pathogens: Do viruses/phages hold the key?

    PubMed Central

    Gill, Erin E; Brinkman, Fiona S L

    2011-01-01

    Although Archaea inhabit the human body and possess some characteristics of pathogens, there is a notable lack of pathogenic archaeal species identified to date. We hypothesize that the scarcity of disease-causing Archaea is due, in part, to mutually-exclusive phage and virus populations infecting Bacteria and Archaea, coupled with an association of bacterial virulence factors with phages or mobile elements. The ability of bacterial phages to infect Bacteria and then use them as a vehicle to infect eukaryotes may be difficult for archaeal viruses to evolve independently. Differences in extracellular structures between Bacteria and Archaea would make adsorption of bacterial phage particles onto Archaea (i.e. horizontal transfer of virulence) exceedingly hard. If phage and virus populations are indeed exclusive to their respective host Domains, this has important implications for both the evolution of pathogens and approaches to infectious disease control. PMID:21328413

  16. Associations between Parenting Behaviors and Adolescent Romantic Relationships

    PubMed Central

    Auslander, Beth A.; Short, Mary B.; Succop, Paul A.; Rosenthal, Susan L.

    2014-01-01

    We examined associations between parenting behaviors and romantic relationship qualities in 102 adolescent girls (14–21 years) who lived with their parent/parental figure and had current boyfriends. Adolescent girls’ perceptions that parents were accepting/involved and provided appropriate strictness and supervision were significantly related to adolescent girls’ perceptions of mutuality (i.e., bidirectional movement of thoughts, feelings, and activities between persons) [1] within their own romantic relationships which in turn was related to their romantic relationship satisfaction. No parenting variables were related to non-exclusivity. PMID:19541257

  17. Operation Condition Monitoring using Temporal Weighted Dempster-Shafer Theory

    DTIC Science & Technology

    2014-12-23

    are mutually exclusive; A mapping of  : 2 0,1m   , which defines the basic probability assignment( BPA ) of each subset A  of hypotheses and...satisfying ( ) 0;m   ( ) 1 A m A   . The BPA represents a certain piece of ev idence. A rule of D-S evidence combination, which could be used to...yield a new BPA from two independent evidences and their BPAs . There are a number of possible combination rules in application (Sentz, 2002). One

  18. Silymarin for hepatitis C virus infection

    PubMed Central

    Polyak, Stephen J; Oberlies, Nicholas H; Pécheur, Eve-Isabelle; Dahari, Harel; Ferenci, Peter; Pawlotsky, Jean-Michel

    2014-01-01

    Silymarin, an extract of milk thistle seeds, and silymarin-derived compounds have been considered hepatoprotective since the plant was first described in ancient times. Hepatoprotection is defined as several non-mutually exclusive biological activities including antiviral, antioxidant, anti-inflammatory and immunomodulatory functions. Despite clear evidence for silymarin-induced hepatoprotection in cell culture and animal models, evidence for beneficial effects in humans has been equivocal. This review will summarize the current state of knowledge on silymarin in the context of hepatitis C virus infection. The information was collated from a recent workshop on silibinin in Germany. PMID:23011959

  19. The Most Critical Unresolved Issues Associated with Race, Ethnicity, Culture, and Substance Use

    PubMed Central

    Unger, Jennifer B.

    2015-01-01

    This paper discusses the limitations of previous research on race, ethnicity, culture, and substance use. The study offers the following recommendations for future research in this area: (1) move beyond simple comparisons of mutually exclusive groups, (2) focus on the meaning of an ethnic label to the individual, (3) consider the complex interactions between an individual’s cultural identity and the cultural context, (4) understand and acknowledge the researcher’s inherent biases, and (5) translate research findings into practice and policy change. PMID:22217334

  20. Assessing China’s Soft Power in Asia: Implications for U.S. Strategy

    DTIC Science & Technology

    2012-04-01

    especially as it might be thought of as an instrument of policy.”19 Gray‟s critiques deride the strategic usefulness of soft 8 power based on the length...soft power flows from hard power, but not the reverse. Gray critiques soft power as if it is mutually exclusive of hard power; that is, if you use ...and film …the freedom is not there. (The Chinese government) really tries to control and manage it, and there is self- censorship as well. That is

  1. Success Factors for Adoption of Real-Time Java

    DTIC Science & Technology

    2010-04-01

    use Java in an effective way in order to achieve objectives If d ’t l t ti f bj ti d d ’t lt i t l i 9© 2010 Atego. All rights reserved. you on p an o...order to effectively use object-oriented programming practices. Te ps d’execution des algos 400 450 500 550 600 650 700 n m s TacticalPicture...find all garbage, nor to defragment the available free pool Common operations may have surprising effects (e.g. entering a mutual exclusion region

  2. Mutuality and the social regulation of neural threat responding

    PubMed Central

    Coan, James A.; Kasle, Shelley; Jackson, Alice; Schaefer, Hillary S.; Davidson, Richard J.

    2014-01-01

    Recent studies have shown that the presence of a caring relational partner can attenuate neural responses to threat. Here we report reanalyzed data from Coan, Schaefer, and Davidson (2006), investigating the role of relational mutuality in the neural response to threat. Mutuality reflects the degree to which couple members show mutual interest in the sharing of internal feelings, thoughts, aspirations, and joys – a vital form of responsiveness in attachment relationships. We predicted that wives who were high (versus low) in perceived mutuality, and who attended the study session with their husbands, would show reduced neural threat reactivity in response to mild electric shocks. We also explored whether this effect would depend on physical contact (handholding). As predicted, we observed that higher mutuality scores corresponded with decreased neural threat responding in the right dorsolateral prefrontal cortex and supplementary motor cortex. These effects were independent of hand-holding condition. These findings suggest that higher perceived mutuality corresponds with decreased self-regulatory effort and attenuated preparatory motor activity in response to threat cues, even in the absence of direct physical contact with social resources. PMID:23547803

  3. Epstein-Barr virus latency switch in human B-cells: a physico-chemical model.

    PubMed

    Werner, Maria; Ernberg, Ingemar; Zou, Jiezhi; Almqvist, Jenny; Aurell, Erik

    2007-08-31

    The Epstein-Barr virus is widespread in all human populations and is strongly associated with human disease, ranging from infectious mononucleosis to cancer. In infected cells the virus can adopt several different latency programs, affecting the cells' behaviour. Experimental results indicate that a specific genetic switch between viral latency programs, reprograms human B-cells between proliferative and resting states. Each of these two latency programs makes use of a different viral promoter, Cp and Qp, respectively. The hypothesis tested in this study is that this genetic switch is controlled by both human and viral transcription factors; Oct-2 and EBNA-1. We build a physico-chemical model to investigate quantitatively the dynamical properties of the promoter regulation and experimentally examine protein level variations between the two latency programs. Our experimental results display significant differences in EBNA-1 and Oct-2 levels between resting and proliferating programs. With the model we identify two stable latency programs, corresponding to a resting and proliferating cell. The two programs differ in robustness and transcriptional activity. The proliferating state is markedly more stable, with a very high transcriptional activity from its viral promoter. We predict the promoter activities to be mutually exclusive in the two different programs, and our relative promoter activities correlate well with experimental data. Transitions between programs can be induced, by affecting the protein levels of our transcription factors. Simulated time scales are in line with experimental results. We show that fundamental properties of the Epstein-Barr virus involvement in latent infection, with implications for tumor biology, can be modelled and understood mathematically. We conclude that EBNA-1 and Oct-2 regulation of Cp and Qp is sufficient to establish mutually exclusive expression patterns. Moreover, the modelled genetic control predict both mono- and bistable behavior and a considerable difference in transition dynamics, based on program stability and promoter activities. Both these phenomena we hope can be further investigated experimentally, to increase the understanding of this important switch. Our results also stress the importance of the little known regulation of human transcription factor Oct-2.

  4. Using Single-Nucleotide Polymorphisms To Discriminate Disease-Associated from Carried Genomes of Neisseria meningitidis▿†

    PubMed Central

    Katz, Lee S.; Sharma, Nitya V.; Harcourt, Brian H.; Thomas, Jennifer Dolan; Wang, Xin; Mayer, Leonard W.; Jordan, I. King

    2011-01-01

    Neisseria meningitidis is one of the main agents of bacterial meningitis, causing substantial morbidity and mortality worldwide. However, most of the time N. meningitidis is carried as a commensal not associated with invasive disease. The genomic basis of the difference between disease-associated and carried isolates of N. meningitidis may provide critical insight into mechanisms of virulence, yet it has remained elusive. Here, we have taken a comparative genomics approach to interrogate the difference between disease-associated and carried isolates of N. meningitidis at the level of individual nucleotide variations (i.e., single nucleotide polymorphisms [SNPs]). We aligned complete genome sequences of 8 disease-associated and 4 carried isolates of N. meningitidis to search for SNPs that show mutually exclusive patterns of variation between the two groups. We found 63 SNPs that distinguish the 8 disease-associated genomes from the 4 carried genomes of N. meningitidis, which is far more than can be expected by chance alone given the level of nucleotide variation among the genomes. The putative list of SNPs that discriminate between disease-associated and carriage genomes may be expected to change with increased sampling or changes in the identities of the isolates being compared. Nevertheless, we show that these discriminating SNPs are more likely to reflect phenotypic differences than shared evolutionary history. Discriminating SNPs were mapped to genes, and the functions of the genes were evaluated for possible connections to virulence mechanisms. A number of overrepresented functional categories related to virulence were uncovered among SNP-associated genes, including genes related to the category “symbiosis, encompassing mutualism through parasitism.” PMID:21622743

  5. Ultra-tough and strong, hybrid thin films based on ionically crosslinked polymers and 2D inorganic platelets

    NASA Astrophysics Data System (ADS)

    Ji, Dong Hwan; Choi, Suji; Kim, Jaeyun; nanobiomaterials lab Team

    Integration of high strength and toughness tend to be mutually exclusive and synthesized hybrid films with superior mechanical properties have been difficult to fabricate controllable shapes and various scales. Although diverse synthesized hybrid films consisting of organic matrix and inorganic materials with brick-and-mortar structure, show improved mechanical properties, these films are still limited in toughness and fabrication methods. Herein, we report ultra-tough and strong hybrid thin films with self-assembled uniform microstructures with controllable shapes and various scale based on hydrogel-mediated process. Ca2+-crosslinking in alginate chains and well-aligned alumina platelets in alginate matrix lead to a synergistic enhancement of strength and toughness in the resulting film. Consequentially, Ca2+-crosslinked Alg/Alu films showed outstanding toughness of 29 MJ m-3 and tensile strength of 160 MPa. Furthermore, modifying Alu surface with polyvinylpyrrolidone (PVP), tensile strength was further improved up to 200 MPa. Our results suggest an alternative approach to design and processing of self-assembled hydrogel-mediated hybrid films with outstanding mechanical properties.

  6. What it feels like to be a mother: Variations by children’s developmental stages

    PubMed Central

    Luthar, Suniya S.; Ciciolla, Lucia

    2015-01-01

    The central question we addressed was whether mothers’ adjustment might vary systematically by the developmental stages of their children. In an internet-based study of over 2,200 mostly well-educated mothers with children ranging from infants to adults, we examined multiple aspects of mothers’ personal well-being, parenting, and perceptions of their children. Uniformly, adjustment indices showed curvilinear patterns across children’s developmental stages, with mothers of middle-schoolers faring the most poorly, and mothers of adult children and infants faring the best. Findings based on children in mutually exclusive age groups -- e.g., mothers with only (one or more) infants, preschoolers, etc. -- had larger effect sizes than those based on the age of the mothers’ oldest child. In contrast to the recurrent findings based on children’s developmental stages, mothers’ adjustment dimensions showed few variations by their children’s gender. Collectively, results of this study suggest that there is value in preventive interventions involving mothers not just in their children’s infancy and preschool years, but also as their children traverse the developmentally challenging years surrounding puberty. PMID:26501727

  7. C/EBPβ LIP and c-Jun synergize to regulate expression of the murine progesterone receptor.

    PubMed

    Wang, Weizhong; Do, Han Ngoc; Aupperlee, Mark D; Durairaj, Srinivasan; Flynn, Emily E; Miksicek, Richard J; Haslam, Sandra Z; Schwartz, Richard C

    2018-06-02

    CCAAT/enhancer binding protein β (C/EBPβ) is required for murine mammary ductal morphogenesis and alveologenesis. Progesterone is critical for proliferation and alveologenesis in adult mammary glands, and there is a similar requirement for progesterone receptor isoform B (PRB) in alveologenesis. We examined C/EBPβ regulation of PR expression. All three C/EBPβ isoforms, including typically inhibitory LIP, transactivated the PR promoter. LIP, particularly, strongly synergized with c-Jun to drive PR transcription. Endogenous C/EBPβ and c-Jun stimulated a PR promoter-reporter and these two factors showed promoter occupancy on the endogenous PR gene. Additionally, LIP overexpression elevated endogenous PR protein expression. In pregnancy, both PRB and the relative abundance of LIP among C/EBPβ isoforms increase. Consistent with a role in PRB expression, in vivo C/EBPβ and PR isoform A expression showed mutually exclusive localization in mammary epithelium, while C/EBPβ and PRB largely co-localized. We suggest a critical role for C/EBPβ, particularly LIP, in PRB expression. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Functional traits determine formation of mutualism and predation interactions in seed-rodent dispersal system of a subtropical forest

    NASA Astrophysics Data System (ADS)

    Chang, Gang; Zhang, Zhibin

    2014-02-01

    Network structure in plant-animal systems has been widely investigated but the roles of functional traits of plants and animals in formation of mutualism and predation interactions and community structure are still not fully understood. In this study, we quantitatively assessed interaction strength of mutualism and predation between 5 tree species and 7 rodent species by using semi-natural enclosures in a subtropical forest in southwest China. Seeds with high handling-time and nutrition traits (for both rat and mouse species) or high tannin trait (for mouse species) show high mutualism but low predation with rodents; while seeds with low handling-time and low nutrition traits show high predation but low mutualism with rodents. Large-sized rat species are more linked to seeds with high handling-time and high nutrition traits, while small-sized mouse species are more connected with seeds with low handling-time, low nutrition value and high tannin traits. Anti-predation seed traits tend to increase chance of mutualism instead of reducing predation by rodents, suggesting formation of mutualism may be connected with that of predation. Our study demonstrates that seed and animal traits play significant roles in the formation of mutualism and predation and network structure of the seed-rodent dispersal system.

  9. Multiple Origins of the Pathogenic Yeast Candida orthopsilosis by Separate Hybridizations between Two Parental Species.

    PubMed

    Schröder, Markus S; Martinez de San Vicente, Kontxi; Prandini, Tâmara H R; Hammel, Stephen; Higgins, Desmond G; Bagagli, Eduardo; Wolfe, Kenneth H; Butler, Geraldine

    2016-11-01

    Mating between different species produces hybrids that are usually asexual and stuck as diploids, but can also lead to the formation of new species. Here, we report the genome sequences of 27 isolates of the pathogenic yeast Candida orthopsilosis. We find that most isolates are diploid hybrids, products of mating between two unknown parental species (A and B) that are 5% divergent in sequence. Isolates vary greatly in the extent of homogenization between A and B, making their genomes a mosaic of highly heterozygous regions interspersed with homozygous regions. Separate phylogenetic analyses of SNPs in the A- and B-derived portions of the genome produces almost identical trees of the isolates with four major clades. However, the presence of two mutually exclusive genotype combinations at the mating type locus, and recombinant mitochondrial genomes diagnostic of inter-clade mating, shows that the species C. orthopsilosis does not have a single evolutionary origin but was created at least four times by separate interspecies hybridizations between parents A and B. Older hybrids have lost more heterozygosity. We also identify two isolates with homozygous genomes derived exclusively from parent A, which are pure non-hybrid strains. The parallel emergence of the same hybrid species from multiple independent hybridization events is common in plant evolution, but is much less documented in pathogenic fungi.

  10. Why power matters: creating a foundation of mutual support in couple relationships.

    PubMed

    Knudson-Martin, Carmen

    2013-03-01

    Research shows that equal power helps couples create intimacy and relationship success. However, though couples increasingly desire equal relationships, cultural models of mutual support are not well developed. Clinicians often approach heterosexual couple therapy as though partners are inherently equal, thus reinforcing unacknowledged gender inequities. This article examines research that shows why power imbalances are destructive to intimate relationships and focuses on four gender-related aspects of mutual support: (a) shared relational responsibility, (b) mutual vulnerability, (c) mutual attunement, and (d) shared influence. Case examples illustrate how socio-emotional attunement, interrupting the flow of power, and introducing alternative relational experience help couple therapists identify and address power disparities in these important relational processes. Encouraging the powerful person to take relational initiative and introducing alternative gender discourse are especially important. © FPI, Inc.

  11. Analysis of Single-cell Gene Transcription by RNA Fluorescent In Situ Hybridization (FISH)

    PubMed Central

    Ronander, Elena; Bengtsson, Dominique C.; Joergensen, Louise; Jensen, Anja T. R.; Arnot, David E.

    2012-01-01

    Adhesion of Plasmodium falciparum infected erythrocytes (IE) to human endothelial receptors during malaria infections is mediated by expression of PfEMP1 protein variants encoded by the var genes. The haploid P. falciparum genome harbors approximately 60 different var genes of which only one has been believed to be transcribed per cell at a time during the blood stage of the infection. How such mutually exclusive regulation of var gene transcription is achieved is unclear, as is the identification of individual var genes or sub-groups of var genes associated with different receptors and the consequence of differential binding on the clinical outcome of P. falciparum infections. Recently, the mutually exclusive transcription paradigm has been called into doubt by transcription assays based on individual P. falciparum transcript identification in single infected erythrocytic cells using RNA fluorescent in situ hybridization (FISH) analysis of var gene transcription by the parasite in individual nuclei of P. falciparum IE1. Here, we present a detailed protocol for carrying out the RNA-FISH methodology for analysis of var gene transcription in single-nuclei of P. falciparum infected human erythrocytes. The method is based on the use of digoxigenin- and biotin- labeled antisense RNA probes using the TSA Plus Fluorescence Palette System2 (Perkin Elmer), microscopic analyses and freshly selected P. falciparum IE. The in situ hybridization method can be used to monitor transcription and regulation of a variety of genes expressed during the different stages of the P. falciparum life cycle and is adaptable to other malaria parasite species and other organisms and cell types. PMID:23070076

  12. The Development of Mutuality in Natural Small Groups.

    ERIC Educational Resources Information Center

    Baker, Paul Morgan

    1983-01-01

    Describes factors affecting the development of mutuality of attraction in natural small groups, and tests the hypothesis of the acquaintance process in 41 female residents of three floors of a university dormitory over the course of a year. Two floors showed definite increases in dyadic mutuality over time. (JAC)

  13. A Secure Base from which to Cooperate: Security, Child and Parent Willing Stance, and Adaptive and Maladaptive Outcomes in two Longitudinal Studies.

    PubMed

    Goffin, Kathryn C; Boldt, Lea J; Kochanska, Grazyna

    2017-10-17

    Early secure attachment plays a key role in socialization by inaugurating a long-term mutual positive, collaborative interpersonal orientation within the parent-child dyad. We report findings from Family Study (community mothers, fathers, and children, from age 2 to 12, N = 102, 51 girls) and Play Study (exclusively low-income mothers and children, from age 3.5 to 7, N = 186, 90 girls). We examined links among observed secure attachment at toddler age, child and parent receptive, willing stance to each other, observed in parent-child contexts at early school age, and developmental outcomes. The developmental outcomes included parent-rated child antisocial behavior problems and observed positive mutuality with regard to conflict issues at age 12 in Family Study, and mother-rated child antisocial behavior problems and observed child regard for rules and moral self at age 7 in Play Study. In mother-child relationships, the child's willing stance mediated indirect effects of child security on positive mutuality in Family Study and on all outcomes in Play Study. In father-child relationships, both the child's and the parent's willing stance mediated indirect effects of child security on both outcomes. Early security initiates an adaptive developmental cascade by enlisting the child and the parent as active, willingly receptive and cooperative agents in the socialization process. Implications for children's parenting interventions are noted.

  14. Comparison of Three Optical Methods for Measuring Model Deformation

    NASA Technical Reports Server (NTRS)

    Burner, A. W.; Fleming, G. A.; Hoppe, J. C.

    2000-01-01

    The objective of this paper is to compare the current state-of-the-art of the following three optical techniques under study by NASA for measuring model deformation in wind tunnels: (1) video photogrammetry, (2) projection moire interferometry, and (3) the commercially available Optotrak system. An objective comparison of these three techniques should enable the selection of the best technique for a particular test undertaken at various NASA facilities. As might be expected, no one technique is best for all applications. The techniques are also not necessarily mutually exclusive and in some cases can be complementary to one another.

  15. Mutational Dynamics of Aroid Chloroplast Genomes

    PubMed Central

    Ahmed, Ibrar; Biggs, Patrick J.; Matthews, Peter J.; Collins, Lesley J.; Hendy, Michael D.; Lockhart, Peter J.

    2012-01-01

    A characteristic feature of eukaryote and prokaryote genomes is the co-occurrence of nucleotide substitution and insertion/deletion (indel) mutations. Although similar observations have also been made for chloroplast DNA, genome-wide associations have not been reported. We determined the chloroplast genome sequences for two morphotypes of taro (Colocasia esculenta; family Araceae) and compared these with four publicly available aroid chloroplast genomes. Here, we report the extent of genome-wide association between direct and inverted repeats, indels, and substitutions in these aroid chloroplast genomes. We suggest that alternative but not mutually exclusive hypotheses explain the mutational dynamics of chloroplast genome evolution. PMID:23204304

  16. Intracranial hypertension in a dieting patient.

    PubMed

    Sirdofsky, M; Kattah, J; Macedo, P

    1994-03-01

    We report a case of encephalopathy with paranoid psychosis in association with intracranial hypertension. This occurred in a patient whose diet consisted almost solely of walnuts, ginseng tea, and vitamin A supplements. The patient was found to be severely iron- and vitamin B12-deficient. She was vitamin A toxic. Venous sinus thrombosis was also present. Symptoms remitted with serial lumbar punctures, normalization of diet, and repletion of vitamin B12 and iron stores. Physicians should be alerted to the possibility of a potentially confusing clinical presentation with coexistent and seemingly mutually exclusive neurologic conditions in patients with extremely restricted or fad diets.

  17. Balancing acts: drag queens, gender and faith.

    PubMed

    Sullivan-Blum, Constance R

    2004-01-01

    While engaged in research on the same-sex marriage debate in mainline denominations, I interviewed 23 LGBT Christians, four of whom were drag queens. While it is not possible to generalize from such a small sample, the drag queens in this study insist on maintaining their identity as Christians despite the hegemonic discourse that renders faith and LGBT identities mutually exclusive. They developed innovative approaches to reconciling their gender and sexual identities with their spirituality. Their innovations are potentially liberating not just for them personally, but for LGBT people generally because they challenge Christianity's rigid dichotomies of gender and sexuality.

  18. Assessing older drivers: a primary care protocol to evaluate driving safety risk.

    PubMed

    Murden, Robert A; Unroe, Kathleen

    2005-08-01

    Most articles on elder drivers offer either general advice, or review testing protocols that divide drivers into two distinct groups: safe or unsafe. We believe it is unreasonable to expect any testing to fully separate drivers into just these two mutually exclusive groups, so we offer a protocol for a more practical approach. This protocol can be applied by primary care physicians. We review the justification for the many steps of this protocol, which have branches that lead to identifying drivers as low risk, high risk (for accidents) or needing further evaluation. Options for further evaluation are provided.

  19. Study: Results and Use of Army Studies

    DTIC Science & Technology

    1976-08-01

    Because the cate- gories are not mutually exclusive, it did not appear useful or enlight - ening to pursue the question of category "level-of-effort." If...AND PERSONNEL 12 3-2 CONCEPTS AND PLANS 25 3-3 OPERATIONS AND FORCE STRUCTURE 32 3-4 LOGISTICS 36 3-5 SCIENCE AND TECHNOLOGY 25 -- 3-6 MANAGEMENT 11...STRUCTURE 24.8% 26.2% 24.1% 21.1% 4-4 LOGISTICS 23.6% 21.9% 18.9% 19.2% 4-5 SCIENCE AND TECHNOLOGY 9.6% 10.0% 11.4% 11.7% 4-6 MANAGEMENT 10.2% 12.8% 13.0

  20. Blood type analyses of creole-like cattle: a comparison with Longhorns and mixed controls.

    PubMed

    Murphey, R M; Torres Penedo, M C; Stormont, C; Bahre, C J

    1979-01-01

    Creole-like cattle blood types were compared with a mixed control group and Longhorn data using hemolytic and electrophoretic techniques. Among the hemolytic tests, the crucial B system analyses indicated that 1) the Creole-like animals were more similar to Longhorns than were the controls; 2) the three groups were different from each other; 3) the three groups were not mutually exclusive. Eleven new phenogroups were postulated. The remaining blood group systems and the electrophoretic tests raised interesting biohistorical questions but were generally less useful in discriminating among the three groups of cattle.

  1. Model checking for linear temporal logic: An efficient implementation

    NASA Technical Reports Server (NTRS)

    Sherman, Rivi; Pnueli, Amir

    1990-01-01

    This report provides evidence to support the claim that model checking for linear temporal logic (LTL) is practically efficient. Two implementations of a linear temporal logic model checker is described. One is based on transforming the model checking problem into a satisfiability problem; the other checks an LTL formula for a finite model by computing the cross-product of the finite state transition graph of the program with a structure containing all possible models for the property. An experiment was done with a set of mutual exclusion algorithms and tested safety and liveness under fairness for these algorithms.

  2. Attitudes toward addiction, methadone treatment, and recovery among HIV-infected Ukrainian prisoners who inject drugs: Incarceration effects and exploration of mediators

    PubMed Central

    Polonsky, Maxim; Rozanova, Julia; Azbel, Lyuba; Bachireddy, Chethan; Izenberg, Jacob; Kiriazova, Tetiana; Dvoryak, Sergii; Altice, Frederick L.

    2016-01-01

    In this study, we use data from a survey conducted in Ukraine among 196 HIV-infected people who inject drugs (PWID), to explore attitudes toward drug addiction and methadone maintenance therapy (MMT), and intentions to change drug use during incarceration and after release from prison. Two groups were recruited: Group 1 (n=99) was currently incarcerated and Group 2 (n=97) had been recently released from prison. This paper’s key finding is that MMT treatment and addiction recovery were predominantly viewed as mutually exclusive processes. Group comparisons showed that participants in Group 1 exhibited higher optimism about changing their drug use, were less likely to endorse methadone, and reported higher intention to recover from their addiction. Group 2 participants, however, reported higher rates of HIV stigma. Structural equation modeling revealed that in both groups, optimism about recovery and awareness of addiction mediated the effect of drug addiction severity on intentions to recover. PMID:27011378

  3. Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

    PubMed

    Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

    2016-08-23

    Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Stimulus specificity and individual stereotypy of autonomic responses to motion stressors. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Morgan, M. G.

    1985-01-01

    Motion sickness research shows a lack of agreement regarding the contribution of the autonomic nervous system (ANS). The resolution of this question is exigent for Space Adaptation Syndrome, zero gravity sickness. A case is drawn for the necessity to apply a methodological approach that incorporates: (1) standardization of parameters in relation to the individual differences in variability and prestimulus levels; (2) a concern for patterning of responses; and (3) the physiological association with subjective reports. Vasomotor, heart rate, respiration rate, skin conductance and subjective reports of malaise were collected from 22 subjects while participating in three motion stressors; vertical acceleration, Coriolis stimulation, and combined optokinetic and Coriolis stimulation. The results demonstrate that ANS response patterns can be separated into three mutually exclusive components: (1) a generalized response to motion sickness; (2) a stimulus specific response to the type of stressor being presented; and (3) individualized stereotypical response patterns that are associated with subjective reports of malaise.

  5. Protein analysis by time-resolved measurements with an electro-switchable DNA chip

    PubMed Central

    Langer, Andreas; Hampel, Paul A.; Kaiser, Wolfgang; Knezevic, Jelena; Welte, Thomas; Villa, Valentina; Maruyama, Makiko; Svejda, Matej; Jähner, Simone; Fischer, Frank; Strasser, Ralf; Rant, Ulrich

    2013-01-01

    Measurements in stationary or mobile phases are fundamental principles in protein analysis. Although the immobilization of molecules on solid supports allows for the parallel analysis of interactions, properties like size or shape are usually inferred from the molecular mobility under the influence of external forces. However, as these principles are mutually exclusive, a comprehensive characterization of proteins usually involves a multi-step workflow. Here we show how these measurement modalities can be reconciled by tethering proteins to a surface via dynamically actuated nanolevers. Short DNA strands, which are switched by alternating electric fields, are employed as capture probes to bind target proteins. By swaying the proteins over nanometre amplitudes and comparing their motional dynamics to a theoretical model, the protein diameter can be quantified with Angström accuracy. Alterations in the tertiary protein structure (folding) and conformational changes are readily detected, and even post-translational modifications are revealed by time-resolved molecular dynamics measurements. PMID:23839273

  6. The Distribution and Cellular Lineages of XX and XY Cells in Gonads Associated with Ovotesticular Disorder of Sexual Development.

    PubMed

    Nishina-Uchida, Noriko; Fukuzawa, Ryuji; Ishii, Tomohiro; Anaka, Matthew R; Hasegawa, Tomonobu; Hasegawa, Yukihiro

    2016-01-01

    Individuals with a 46,XX/46,XY karyotype are categorized as ovotesticular disorder of sexual development (ODSD) and have gonads with either an ovary on one side and a testis on the other side or a mixed ovotestis. To examine the distribution of 46,XX and 46,XY cells in gonads of 3 patients with ODSD, FISH for X and Y chromosomes and immunohistochemistry for SOX9 and FOXL2 were carried out. FISH analysis showed that XX signals were present in Sertoli cells in the seminiferous tubules, while cells containing Y signals were seen in epithelia of ovarian follicles. The immunolabeling of SOX9 and FOXL2 in the seminiferous tubules and ovarian follicles was mutually exclusive, irrespective of the presence of reversed sex chromosomes. We therefore suggest that the fate of individual gonadal epithelial cells is determined not only by the sex chromosomes but also by local environmental factors. © 2016 S. Karger AG, Basel.

  7. Momentum-resolved observations of the phonon instability driving geometric improper ferroelectricity in yttrium manganite

    DOE PAGES

    Bansal, Dipanshu; Niedziela, Jennifer L.; Sinclair, Ryan; ...

    2018-01-02

    Magnetoelectrics offer tantalizing opportunities for devices coupling ferroelectricity and magnetism but remain difficult to realize. Breakthrough strategies could circumvent the mutually exclusive origins of magnetism and ferroelectricity by exploiting the interaction of multiple phonon modes in geometric improper and hybrid improper ferroelectrics. Yet, the proposed instability of a zone-boundary phonon mode, driving the emergence of ferroelectricity via coupling to a polar mode, remains to be directly observed. Here, we provide previously missing evidence for this scenario in the archetypal improper ferroelectric, yttrium manganite, through comprehensive scattering measurements of the atomic structure and phonons, supported with first-principles simulations. Our experiments andmore » theoretical modeling resolve the origin of the unusual temperature dependence of the polarization and rule out a reported double-step ferroelectric transition. These results emphasize the critical role of phonon anharmonicity in rationalizing lattice instabilities in improper ferroelectrics and show that including these effects in simulations could facilitate the design of magnetoelectrics.« less

  8. The development of fast-mapping and novel word retention strategies in monolingual and bilingual infants.

    PubMed

    Kalashnikova, Marina; Escudero, Paola; Kidd, Evan

    2018-04-30

    The mutual exclusivity (ME) assumption is proposed to facilitate early word learning by guiding infants to map novel words to novel referents. This study assessed the emergence and use of ME to both disambiguate and retain the meanings of novel words across development in 18-month-old monolingual and bilingual children (Experiment 1; N = 58), and in a sub-group of these children again at 24 months of age (Experiment 2: N = 32). Both monolinguals and bilinguals employed ME to select the referent of a novel label to a similar extent at 18 and 24 months. At 18 months, there were also no differences in novel word retention between the two language-background groups. However, at 24 months, only monolinguals showed the ability to retain these label-object mappings. These findings indicate that the development of the ME assumption as a reliable word-learning strategy is shaped by children's individual language exposure and experience with language use. © 2018 John Wiley & Sons Ltd.

  9. Testing the risk of predation hypothesis: the influence of recolonizing wolves on habitat use by moose.

    PubMed

    Nicholson, Kerry L; Milleret, Cyril; Månsson, Johan; Sand, Håkan

    2014-09-01

    Considered as absent throughout Scandinavia for >100 years, wolves (Canis lupus) have recently naturally recolonized south-central Sweden. This recolonization has provided an opportunity to study behavioral responses of moose (Alces alces) to wolves. We used satellite telemetry locations from collared moose and wolves to determine whether moose habitat use was affected by predation risk based on wolf use distributions. Moose habitat use was influenced by reproductive status and time of day and showed a different selection pattern between winter and summer, but there was weak evidence that moose habitat use depended on predation risk. The seemingly weak response may have several underlying explanations that are not mutually exclusive from the long term absence of non-human predation pressure: intensive harvest by humans during the last century is more important than wolf predation as an influence on moose behavior; moose have not adapted to recolonizing wolves; and responses may include other behavioral adaptations or occur at finer temporal and spatial levels than investigated.

  10. Momentum-resolved observations of the phonon instability driving geometric improper ferroelectricity in yttrium manganite

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bansal, Dipanshu; Niedziela, Jennifer L.; Sinclair, Ryan

    Magnetoelectrics offer tantalizing opportunities for devices coupling ferroelectricity and magnetism but remain difficult to realize. Breakthrough strategies could circumvent the mutually exclusive origins of magnetism and ferroelectricity by exploiting the interaction of multiple phonon modes in geometric improper and hybrid improper ferroelectrics. Yet, the proposed instability of a zone-boundary phonon mode, driving the emergence of ferroelectricity via coupling to a polar mode, remains to be directly observed. Here, we provide previously missing evidence for this scenario in the archetypal improper ferroelectric, yttrium manganite, through comprehensive scattering measurements of the atomic structure and phonons, supported with first-principles simulations. Our experiments andmore » theoretical modeling resolve the origin of the unusual temperature dependence of the polarization and rule out a reported double-step ferroelectric transition. These results emphasize the critical role of phonon anharmonicity in rationalizing lattice instabilities in improper ferroelectrics and show that including these effects in simulations could facilitate the design of magnetoelectrics.« less

  11. Momentum-resolved observations of the phonon instability driving geometric improper ferroelectricity in yttrium manganite.

    PubMed

    Bansal, Dipanshu; Niedziela, Jennifer L; Sinclair, Ryan; Garlea, V Ovidiu; Abernathy, Douglas L; Chi, Songxue; Ren, Yang; Zhou, Haidong; Delaire, Olivier

    2018-01-02

    Magnetoelectrics offer tantalizing opportunities for devices coupling ferroelectricity and magnetism but remain difficult to realize. Breakthrough strategies could circumvent the mutually exclusive origins of magnetism and ferroelectricity by exploiting the interaction of multiple phonon modes in geometric improper and hybrid improper ferroelectrics. Yet, the proposed instability of a zone-boundary phonon mode, driving the emergence of ferroelectricity via coupling to a polar mode, remains to be directly observed. Here, we provide previously missing evidence for this scenario in the archetypal improper ferroelectric, yttrium manganite, through comprehensive scattering measurements of the atomic structure and phonons, supported with first-principles simulations. Our experiments and theoretical modeling resolve the origin of the unusual temperature dependence of the polarization and rule out a reported double-step ferroelectric transition. These results emphasize the critical role of phonon anharmonicity in rationalizing lattice instabilities in improper ferroelectrics and show that including these effects in simulations could facilitate the design of magnetoelectrics.

  12. Somatic hypermutation in MutS homologue (MSH)3-, MSH6-, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern.

    PubMed

    Wiesendanger, M; Kneitz, B; Edelmann, W; Scharff, M D

    2000-02-07

    Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-)/- and Msh3(-)/-/Msh6(-)/- mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-)/- mice. In contrast, Msh3(-)/- mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.

  13. Cooperative interactions enable singular olfactory receptor expression in mouse olfactory neurons

    PubMed Central

    Monahan, Kevin; Schieren, Ira; Cheung, Jonah; Mumbey-Wafula, Alice; Monuki, Edwin S

    2017-01-01

    The monogenic and monoallelic expression of only one out of >1000 mouse olfactory receptor (ORs) genes requires the formation of large heterochromatic chromatin domains that sequester the OR gene clusters. Within these domains, intergenic transcriptional enhancers evade heterochromatic silencing and converge into interchromosomal hubs that assemble over the transcriptionally active OR. The significance of this nuclear organization in OR choice remains elusive. Here, we show that transcription factors Lhx2 and Ebf specify OR enhancers by binding in a functionally cooperative fashion to stereotypically spaced motifs that defy heterochromatin. Specific displacement of Lhx2 and Ebf from OR enhancers resulted in pervasive, long-range, and trans downregulation of OR transcription, whereas pre-assembly of a multi-enhancer hub increased the frequency of OR choice in cis. Our data provide genetic support for the requirement and sufficiency of interchromosomal interactions in singular OR choice and generate general regulatory principles for stochastic, mutually exclusive gene expression programs. PMID:28933695

  14. A metamorphic inorganic framework that can be switched between eight single-crystalline states

    NASA Astrophysics Data System (ADS)

    Zhan, Caihong; Cameron, Jamie M.; Gabb, David; Boyd, Thomas; Winter, Ross S.; Vilà-Nadal, Laia; Mitchell, Scott G.; Glatzel, Stefan; Breternitz, Joachim; Gregory, Duncan H.; Long, De-Liang; MacDonell, Andrew; Cronin, Leroy

    2017-02-01

    The design of highly flexible framework materials requires organic linkers, whereas inorganic materials are more robust but inflexible. Here, by using linkable inorganic rings made up of tungsten oxide (P8W48O184) building blocks, we synthesized an inorganic single crystal material that can undergo at least eight different crystal-to-crystal transformations, with gigantic crystal volume contraction and expansion changes ranging from -2,170 to +1,720 Å3 with no reduction in crystallinity. Not only does this material undergo the largest single crystal-to-single crystal volume transformation thus far reported (to the best of our knowledge), the system also shows conformational flexibility while maintaining robustness over several cycles in the reversible uptake and release of guest molecules switching the crystal between different metamorphic states. This material combines the robustness of inorganic materials with the flexibility of organic frameworks, thereby challenging the notion that flexible materials with robustness are mutually exclusive.

  15. Equilibrium and non-equilibrium dynamics simultaneously operate in the Galápagos islands.

    PubMed

    Valente, Luis M; Phillimore, Albert B; Etienne, Rampal S

    2015-08-01

    Island biotas emerge from the interplay between colonisation, speciation and extinction and are often the scene of spectacular adaptive radiations. A common assumption is that insular diversity is at a dynamic equilibrium, but for remote islands, such as Hawaii or Galápagos, this idea remains untested. Here, we reconstruct the temporal accumulation of terrestrial bird species of the Galápagos using a novel phylogenetic method that estimates rates of biota assembly for an entire community. We show that species richness on the archipelago is in an ascending phase and does not tend towards equilibrium. The majority of the avifauna diversifies at a slow rate, without detectable ecological limits. However, Darwin's finches form an exception: they rapidly reach a carrying capacity and subsequently follow a coalescent-like diversification process. Together, these results suggest that avian diversity of remote islands is rising, and challenge the mutual exclusivity of the non-equilibrium and equilibrium ecological paradigms. © 2015 The Authors Ecology Letters published by John Wiley & Sons Ltd and CNRS.

  16. Reconsidering Emotion Dysregulation.

    PubMed

    D'Agostino, Alessandra; Covanti, Serena; Rossi Monti, Mario; Starcevic, Vladan

    2017-12-01

    This article aims to review the concept of emotion dysregulation, focusing on issues related to its definition, meanings and role in psychiatric disorders. Articles on emotion dysregulation published until May 2016 were identified through electronic database searches. Although there is no agreement about the definition of emotion dysregulation, the following five overlapping, not mutually exclusive dimensions of emotion dysregulation were identified: decreased emotional awareness, inadequate emotional reactivity, intense experience and expression of emotions, emotional rigidity and cognitive reappraisal difficulty. These dimensions characterise a number of psychiatric disorders in various proportions, with borderline personality disorder and eating disorders seemingly more affected than other conditions. The present review contributes to the literature by identifying the key components of emotion dysregulation and by showing how these permeate various forms of psychopathology. It also makes suggestions for improving research endeavours. Better understanding of the various dimensions of emotion dysregulation will have implications for clinical practice. Future research needs to address emotion dysregulation in all its multifaceted complexity so that it becomes clearer what the concept encompasses.

  17. A DNA methylation map of human cancer at single base-pair resolution.

    PubMed

    Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

    2017-10-05

    Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination.

  18. Distinct function of estrogen receptor α in smooth muscle and fibroblast cells in prostate development.

    PubMed

    Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

    2013-01-01

    Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development.

  19. Mutually unbiased coarse-grained measurements of two or more phase-space variables

    NASA Astrophysics Data System (ADS)

    Paul, E. C.; Walborn, S. P.; Tasca, D. S.; Rudnicki, Łukasz

    2018-05-01

    Mutual unbiasedness of the eigenstates of phase-space operators—such as position and momentum, or their standard coarse-grained versions—exists only in the limiting case of infinite squeezing. In Phys. Rev. Lett. 120, 040403 (2018), 10.1103/PhysRevLett.120.040403, it was shown that mutual unbiasedness can be recovered for periodic coarse graining of these two operators. Here we investigate mutual unbiasedness of coarse-grained measurements for more than two phase-space variables. We show that mutual unbiasedness can be recovered between periodic coarse graining of any two nonparallel phase-space operators. We illustrate these results through optics experiments, using the fractional Fourier transform to prepare and measure mutually unbiased phase-space variables. The differences between two and three mutually unbiased measurements is discussed. Our results contribute to bridging the gap between continuous and discrete quantum mechanics, and they could be useful in quantum-information protocols.

  20. Using speakers' referential intentions to model early cross-situational word learning.

    PubMed

    Frank, Michael C; Goodman, Noah D; Tenenbaum, Joshua B

    2009-05-01

    Word learning is a "chicken and egg" problem. If a child could understand speakers' utterances, it would be easy to learn the meanings of individual words, and once a child knows what many words mean, it is easy to infer speakers' intended meanings. To the beginning learner, however, both individual word meanings and speakers' intentions are unknown. We describe a computational model of word learning that solves these two inference problems in parallel, rather than relying exclusively on either the inferred meanings of utterances or cross-situational word-meaning associations. We tested our model using annotated corpus data and found that it inferred pairings between words and object concepts with higher precision than comparison models. Moreover, as the result of making probabilistic inferences about speakers' intentions, our model explains a variety of behavioral phenomena described in the word-learning literature. These phenomena include mutual exclusivity, one-trial learning, cross-situational learning, the role of words in object individuation, and the use of inferred intentions to disambiguate reference.

  1. Efficient multitasking: parallel versus serial processing of multiple tasks

    PubMed Central

    Fischer, Rico; Plessow, Franziska

    2015-01-01

    In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling. PMID:26441742

  2. Efficient multitasking: parallel versus serial processing of multiple tasks.

    PubMed

    Fischer, Rico; Plessow, Franziska

    2015-01-01

    In the context of performance optimizations in multitasking, a central debate has unfolded in multitasking research around whether cognitive processes related to different tasks proceed only sequentially (one at a time), or can operate in parallel (simultaneously). This review features a discussion of theoretical considerations and empirical evidence regarding parallel versus serial task processing in multitasking. In addition, we highlight how methodological differences and theoretical conceptions determine the extent to which parallel processing in multitasking can be detected, to guide their employment in future research. Parallel and serial processing of multiple tasks are not mutually exclusive. Therefore, questions focusing exclusively on either task-processing mode are too simplified. We review empirical evidence and demonstrate that shifting between more parallel and more serial task processing critically depends on the conditions under which multiple tasks are performed. We conclude that efficient multitasking is reflected by the ability of individuals to adjust multitasking performance to environmental demands by flexibly shifting between different processing strategies of multiple task-component scheduling.

  3. A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Deng, Lu; Velikovsky, C. Alejandro; Xu, Gang

    Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called 'variable lymphocyte receptors' (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like {gamma}{delta} T-cell receptors (TCRs) but unlike {alpha}{beta} TCRs, can recognize antigens directly, without a requirement for processing or antigen-presenting molecules. Thus,more » these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and {gamma}{delta} TCRs, and the exclusive expression on the lymphocyte surface that is unique to {alpha}{beta} and {gamma}{delta} TCRs.« less

  4. Hookah and Cigarette Smoking Among African American College Students: Implications for Campus Risk Reduction and Health Promotion Efforts

    PubMed Central

    Jones, Brittni D.; Cunningham-Williams, Renee M.

    2016-01-01

    Objective To identify individual and institutional risks and protections for hookah and cigarette smoking among African American (AA) college students. Participants AA college students (n=1,402; mean age=20, range=18–24 years; 75% female) who completed the Fall 2012 American College Health Association–National College Health Assessment II. Methods Respondents were stratified into four mutually exclusive groups by last 30-day smoking status: cigarette-only use (5.1%), hookah-only use (5.9%), dual use (2.4%), and non-use (86.6%). Multinomial logistic regression models identified the relative odds of exclusive and dual hookah and cigarette smoking. Results Current hookah and cigarette smoking rates were comparably low. Age, gender identity, current substance use, interest in tobacco use information, and student population prevailed as risks and protections for hookah and cigarette smoking. Conclusions Campus health promotion campaigns may need to tailor messages to AA students, particularly those who use substances, to underscore the health risks of hookah and cigarette smoking. PMID:26829515

  5. Multimodal registration via spatial-context mutual information.

    PubMed

    Yi, Zhao; Soatto, Stefano

    2011-01-01

    We propose a method to efficiently compute mutual information between high-dimensional distributions of image patches. This in turn is used to perform accurate registration of images captured under different modalities, while exploiting their local structure otherwise missed in traditional mutual information definition. We achieve this by organizing the space of image patches into orbits under the action of Euclidean transformations of the image plane, and estimating the modes of a distribution in such an orbit space using affinity propagation. This way, large collections of patches that are equivalent up to translations and rotations are mapped to the same representative, or "dictionary element". We then show analytically that computing mutual information for a joint distribution in this space reduces to computing mutual information between the (scalar) label maps, and between the transformations mapping each patch into its closest dictionary element. We show that our approach improves registration performance compared with the state of the art in multimodal registration, using both synthetic and real images with quantitative ground truth.

  6. A cross-linguistic investigation of the acquisition of the pragmatics of indefinite and definite reference in two-year-olds.

    PubMed

    Rozendaal, Margot Isabella; Baker, Anne Edith

    2008-11-01

    The acquisition of reference involves both morphosyntax and pragmatics. This study investigates whether Dutch, English and French two- to three-year-old children differentiate in their use of determiners between non-specific/specific reference, newness/givenness in discourse and mutual/no mutual knowledge between interlocutors. A brief analysis of the input shows a clear association between form and function, although there are some language differences in this respect. As soon as determiner use can be statistically analyzed, the children show a relatively adult-like pattern of association for the distinctions of non-specific/specific and newness/givenness. The distinction between mutual/no mutual knowledge appears later. Reference involving no mutual knowledge is scarcely evidenced in the input and barely used by the children at this age. The development of associations is clearly related to the rate of determiner development, the French being quickest, then the English, then the Dutch.

  7. Improved coverage of cDNA-AFLP by sequential digestion of immobilized cDNA.

    PubMed

    Weiberg, Arne; Pöhler, Dirk; Morgenstern, Burkhard; Karlovsky, Petr

    2008-10-13

    cDNA-AFLP is a transcriptomics technique which does not require prior sequence information and can therefore be used as a gene discovery tool. The method is based on selective amplification of cDNA fragments generated by restriction endonucleases, electrophoretic separation of the products and comparison of the band patterns between treated samples and controls. Unequal distribution of restriction sites used to generate cDNA fragments negatively affects the performance of cDNA-AFLP. Some transcripts are represented by more than one fragment while other escape detection, causing redundancy and reducing the coverage of the analysis, respectively. With the goal of improving the coverage of cDNA-AFLP without increasing its redundancy, we designed a modified cDNA-AFLP protocol. Immobilized cDNA is sequentially digested with several restriction endonucleases and the released DNA fragments are collected in mutually exclusive pools. To investigate the performance of the protocol, software tool MECS (Multiple Enzyme cDNA-AFLP Simulation) was written in Perl. cDNA-AFLP protocols described in the literature and the new sequential digestion protocol were simulated on sets of cDNA sequences from mouse, human and Arabidopsis thaliana. The redundancy and coverage, the total number of PCR reactions, and the average fragment length were calculated for each protocol and cDNA set. Simulation revealed that sequential digestion of immobilized cDNA followed by the partitioning of released fragments into mutually exclusive pools outperformed other cDNA-AFLP protocols in terms of coverage, redundancy, fragment length, and the total number of PCRs. Primers generating 30 to 70 amplicons per PCR provided the highest fraction of electrophoretically distinguishable fragments suitable for normalization. For A. thaliana, human and mice transcriptome, the use of two marking enzymes and three sequentially applied releasing enzymes for each of the marking enzymes is recommended.

  8. The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients.

    PubMed

    Zill, Oliver A; Banks, Kimberly C; Fairclough, Stephen R; Mortimer, Stefanie; Vowles, James V; Mokhtari, Reza; Gandara, David R; Mack, Philip C; Odegaard, Justin I; Nagy, Rebecca J; Baca, Arthur M; Eltoukhy, Helmy; Chudova, Darya I; Lanman, Richard B; Talasaz, AmirAli

    2018-05-18

    Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality. Patterns and prevalence of cfDNA alterations in major driver genes for non-small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (TCGA and COSMIC; r=0.90-0.99), with the principle differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naïve tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR=5x10 -7 for EGFR and ERBB2 ), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (>18.6% patients). Together these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. Copyright ©2018, American Association for Cancer Research.

  9. Strategies and practices in off-label marketing of pharmaceuticals: a retrospective analysis of whistleblower complaints.

    PubMed

    Kesselheim, Aaron S; Mello, Michelle M; Studdert, David M

    2011-04-01

    Despite regulatory restrictions, off-label marketing of pharmaceutical products has been common in the US. However, the scope of off-label marketing remains poorly characterized. We developed a typology for the strategies and practices that constitute off-label marketing. We obtained unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing (January 1996-October 2010) and conducted structured reviews of them. We coded and analyzed the strategic goals of each off-label marketing scheme and the practices used to achieve those goals, as reported by the whistleblowers. We identified 41 complaints arising from 18 unique cases for our analytic sample (leading to US$7.9 billion in recoveries). The off-label marketing schemes described in the complaints had three non-mutually exclusive goals: expansions to unapproved diseases (35/41, 85%), unapproved disease subtypes (22/41, 54%), and unapproved drug doses (14/41, 34%). Manufacturers were alleged to have pursued these goals using four non-mutually exclusive types of marketing practices: prescriber-related (41/41, 100%), business-related (37/41, 90%), payer-related (23/41, 56%), and consumer-related (18/41, 44%). Prescriber-related practices, the centerpiece of company strategies, included self-serving presentations of the literature (31/41, 76%), free samples (8/41, 20%), direct financial incentives to physicians (35/41, 85%), and teaching (22/41, 54%) and research activities (8/41, 20%). Off-label marketing practices appear to extend to many areas of the health care system. Unfortunately, the most common alleged off-label marketing practices also appear to be the most difficult to control through external regulatory approaches.

  10. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans

    PubMed Central

    Lange, Karen I.; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

    2013-01-01

    Summary Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B′, B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo. PMID:23336080

  11. Suppressor mutations identify amino acids in PAA-1/PR65 that facilitate regulatory RSA-1/B″ subunit targeting of PP2A to centrosomes in C. elegans.

    PubMed

    Lange, Karen I; Heinrichs, Jeffrey; Cheung, Karen; Srayko, Martin

    2013-01-15

    Protein phosphorylation and dephosphorylation is a key mechanism for the spatial and temporal regulation of many essential developmental processes and is especially prominent during mitosis. The multi-subunit protein phosphatase 2A (PP2A) enzyme plays an important, yet poorly characterized role in dephosphorylating proteins during mitosis. PP2As are heterotrimeric complexes comprising a catalytic, structural, and regulatory subunit. Regulatory subunits are mutually exclusive and determine subcellular localization and substrate specificity of PP2A. At least 3 different classes of regulatory subunits exist (termed B, B', B″) but there is no obvious similarity in primary sequence between these classes. Therefore, it is not known how these diverse regulatory subunits interact with the same holoenzyme to facilitate specific PP2A functions in vivo. The B″ family of regulatory subunits is the least understood because these proteins lack conserved structural domains. RSA-1 (regulator of spindle assembly) is a regulatory B″ subunit required for mitotic spindle assembly in Caenorhabditis elegans. In order to address how B″ subunits interact with the PP2A core enzyme, we focused on a conditional allele, rsa-1(or598ts), and determined that this mutation specifically disrupts the protein interaction between RSA-1 and the PP2A structural subunit, PAA-1. Through genetic screening, we identified a putative interface on the PAA-1 structural subunit that interacts with a defined region of RSA-1/B″. In the context of previously published results, these data propose a mechanism of how different PP2A B-regulatory subunit families can bind the same holoenzyme in a mutually exclusive manner, to perform specific tasks in vivo.

  12. Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints

    PubMed Central

    Kesselheim, Aaron S.; Mello, Michelle M.; Studdert, David M.

    2011-01-01

    Background Despite regulatory restrictions, off-label marketing of pharmaceutical products has been common in the US. However, the scope of off-label marketing remains poorly characterized. We developed a typology for the strategies and practices that constitute off-label marketing. Methods and Findings We obtained unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing (January 1996–October 2010) and conducted structured reviews of them. We coded and analyzed the strategic goals of each off-label marketing scheme and the practices used to achieve those goals, as reported by the whistleblowers. We identified 41 complaints arising from 18 unique cases for our analytic sample (leading to US$7.9 billion in recoveries). The off-label marketing schemes described in the complaints had three non–mutually exclusive goals: expansions to unapproved diseases (35/41, 85%), unapproved disease subtypes (22/41, 54%), and unapproved drug doses (14/41, 34%). Manufacturers were alleged to have pursued these goals using four non–mutually exclusive types of marketing practices: prescriber-related (41/41, 100%), business-related (37/41, 90%), payer-related (23/41, 56%), and consumer-related (18/41, 44%). Prescriber-related practices, the centerpiece of company strategies, included self-serving presentations of the literature (31/41, 76%), free samples (8/41, 20%), direct financial incentives to physicians (35/41, 85%), and teaching (22/41, 54%) and research activities (8/41, 20%). Conclusions Off-label marketing practices appear to extend to many areas of the health care system. Unfortunately, the most common alleged off-label marketing practices also appear to be the most difficult to control through external regulatory approaches. Please see later in the article for the Editors' Summary PMID:21483716

  13. Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events.

    PubMed

    Quintanilla-Martinez, Leticia; Kremer, Marcus; Specht, Katja; Calzada-Wack, Julia; Nathrath, Michaela; Schaich, Robert; Höfler, Heinz; Fend, Falko

    2003-05-01

    The signal transducer and activator of transcription molecules (Stats) play key roles in cytokine-induced signal transduction. Recently, it was proposed that constitutively activated Stat 3 (Stat 3 phosphorylated) contributes to the pathogenesis of multiple myeloma (MM) by preventing apoptosis and inducing proliferation. The study aim was to investigate Stat 3 activation in a series of multiple myeloma (MM) cases and its effect on downstream targets such as the anti-apoptotic proteins Bcl-xL, Mcl-1, and Bcl-2, and the cell-cycle protein cyclin D1. Forty-eight cases of MM were analyzed. Immunohistochemistry was performed on paraffin sections using antibodies against cyclin D1, Bcl-2, Bcl-xL, Mcl-1, p21, Stat 3, and Stat 3 phosphorylated (P). Their specificity was corroborated by Western blot analysis using eight human MM cell lines as control. The proliferation rate was assessed with the antibody MiB1. In addition, the mRNA levels of cyclin D1 and Stat 3 were determined by quantitative real-time reverse transcriptase-polymerase chain reaction of paraffin-embedded microdissected tissue. Three different groups determined by the expression of Stat 3P and cyclin D1 (protein and mRNA) were identified: group 1, Stat 3-activated (23 cases, 48%). All cases revealed nuclear expression of Stat 3P. No elevation of Stat 3 mRNA was identified in any of the cases. Three cases in this group showed intermediate to low cyclin D1 protein and mRNA expression. Group 2 included 15 (31%) cases with cyclin D1 staining and lack of Stat 3P. All cases showed intermediate to high levels of cyclin D1 mRNA expression. Group 3 included 10 (21%) cases with no expression of either cyclin D1 or Stat 3P. High levels of anti-apoptotic proteins Bcl-xL and Mcl-1 were identified in 89% and 100% of all cases, respectively. In contrast to Bcl-xL and Mcl-1, the expression of Bcl-2 showed an inverse correlation with proliferation rate (P: 0.0003). No significant differences were found between the three groups in terms of proliferation rate or expression of anti-apoptotic proteins. However, cyclin D1+ cases were always well differentiated and were more likely to show a lymphoplasmocytoid differentiation (chi-square = 9.55). Overall, constitutive activation of Stat 3 was found in almost half (48%) of the investigated MM cases. However, this does not seem to have a major impact on the expression of anti-apoptotic proteins and proliferation. We showed that cyclin D1 overexpression and Stat 3 activation are, mutually exclusive events in MM (P = 0.0066). The universal expression of Mcl-1, independent of activated Stat 3, suggests that its expression is constitutive and that it might play an important role in the pathogenesis of MM.

  14. Size exclusion deep bed filtration: Experimental and modelling uncertainties

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Badalyan, Alexander, E-mail: alexander.badalyan@adelaide.edu.au; You, Zhenjiang; Aji, Kaiser

    A detailed uncertainty analysis associated with carboxyl-modified latex particle capture in glass bead-formed porous media enabled verification of the two theoretical stochastic models for prediction of particle retention due to size exclusion. At the beginning of this analysis it is established that size exclusion is a dominant particle capture mechanism in the present study: calculated significant repulsive Derjaguin-Landau-Verwey-Overbeek potential between latex particles and glass beads is an indication of their mutual repulsion, thus, fulfilling the necessary condition for size exclusion. Applying linear uncertainty propagation method in the form of truncated Taylor's series expansion, combined standard uncertainties (CSUs) in normalised suspendedmore » particle concentrations are calculated using CSUs in experimentally determined parameters such as: an inlet volumetric flowrate of suspension, particle number in suspensions, particle concentrations in inlet and outlet streams, particle and pore throat size distributions. Weathering of glass beads in high alkaline solutions does not appreciably change particle size distribution, and, therefore, is not considered as an additional contributor to the weighted mean particle radius and corresponded weighted mean standard deviation. Weighted mean particle radius and LogNormal mean pore throat radius are characterised by the highest CSUs among all experimental parameters translating to high CSU in the jamming ratio factor (dimensionless particle size). Normalised suspended particle concentrations calculated via two theoretical models are characterised by higher CSUs than those for experimental data. The model accounting the fraction of inaccessible flow as a function of latex particle radius excellently predicts normalised suspended particle concentrations for the whole range of jamming ratios. The presented uncertainty analysis can be also used for comparison of intra- and inter-laboratory particle size exclusion data.« less

  15. Population dynamics and mutualism: Functional responses of benefits and costs

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.; Bronstein, Judith L.

    2002-01-01

    We develop an approach for studying population dynamics resulting from mutualism by employing functional responses based on density‐dependent benefits and costs. These functional responses express how the population growth rate of a mutualist is modified by the density of its partner. We present several possible dependencies of gross benefits and costs, and hence net effects, to a mutualist as functions of the density of its partner. Net effects to mutualists are likely a monotonically saturating or unimodal function of the density of their partner. We show that fundamental differences in the growth, limitation, and dynamics of a population can occur when net effects to that population change linearly, unimodally, or in a saturating fashion. We use the mutualism between senita cactus and its pollinating seed‐eating moth as an example to show the influence of different benefit and cost functional responses on population dynamics and stability of mutualisms. We investigated two mechanisms that may alter this mutualism's functional responses: distribution of eggs among flowers and fruit abortion. Differences in how benefits and costs vary with density can alter the stability of this mutualism. In particular, fruit abortion may allow for a stable equilibrium where none could otherwise exist.

  16. Two-year-olds exclude novel objects as potential referents of novel words based on pragmatics.

    PubMed

    Grassmann, Susanne; Stracke, Marén; Tomasello, Michael

    2009-09-01

    Many studies have established that children tend to exclude objects for which they already have a name as potential referents of novel words. In the current study we asked whether this exclusion can be triggered by social-pragmatic context alone without pre-existing words as blockers. Two-year-old children watched an adult looking at a novel object while saying a novel word with excitement. In one condition the adult had not seen the object beforehand, and so the children interpreted the adult's utterance as referring to the gazed-at object. In another condition the adult and child had previously played jointly with the gazed-at object. In this case, children less often assumed that the adult was referring to the object but rather they searched for an alternative referent--presumably because they inferred that the gazed-at object was old news in their common ground with the adult and so not worthy of excited labeling. Since this inference based on exclusion is highly similar to that underlying the Principle of Contrast/Mutual Exclusivity, we propose that this principle is not purely lexical but rather is based on children's understanding of how and why people direct one another's attention to things either with or without language.

  17. MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system

    PubMed Central

    Kapsimali, Marika; Kloosterman, Wigard P; de Bruijn, Ewart; Rosa, Frederic; Plasterk, Ronald HA; Wilson, Stephen W

    2007-01-01

    Background MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied in any detail. Bioinformatic tools allow prediction of miRNA targets and this information coupled with knowledge of miRNA expression profiles facilitates formulation of hypotheses of miRNA function. Although the central nervous system (CNS) is a prominent site of miRNA expression, virtually nothing is known about the spatial and temporal expression profiles of miRNAs in the brain. To provide an overview of the breadth of miRNA expression in the CNS, we performed a comprehensive analysis of the neuroanatomical expression profiles of 38 abundant conserved miRNAs in developing and adult zebrafish brain. Results Our results show miRNAs have a wide variety of different expression profiles in neural cells, including: expression in neuronal precursors and stem cells (for example, miR-92b); expression associated with transition from proliferation to differentiation (for example, miR-124); constitutive expression in mature neurons (miR-124 again); expression in both proliferative cells and their differentiated progeny (for example, miR-9); regionally restricted expression (for example, miR-222 in telencephalon); and cell-type specific expression (for example, miR-218a in motor neurons). Conclusion The data we present facilitate prediction of likely modes of miRNA function in the CNS and many miRNA expression profiles are consistent with the mutual exclusion mode of function in which there is spatial or temporal exclusion of miRNAs and their targets. However, some miRNAs, such as those with cell-type specific expression, are more likely to be co-expressed with their targets. Our data provide an important resource for future functional studies of miRNAs in the CNS. PMID:17711588

  18. Economic contract theory tests models of mutualism.

    PubMed

    Weyl, E Glen; Frederickson, Megan E; Yu, Douglas W; Pierce, Naomi E

    2010-09-07

    Although mutualisms are common in all ecological communities and have played key roles in the diversification of life, our current understanding of the evolution of cooperation applies mostly to social behavior within a species. A central question is whether mutualisms persist because hosts have evolved costly punishment of cheaters. Here, we use the economic theory of employment contracts to formulate and distinguish between two mechanisms that have been proposed to prevent cheating in host-symbiont mutualisms, partner fidelity feedback (PFF) and host sanctions (HS). Under PFF, positive feedback between host fitness and symbiont fitness is sufficient to prevent cheating; in contrast, HS posits the necessity of costly punishment to maintain mutualism. A coevolutionary model of mutualism finds that HS are unlikely to evolve de novo, and published data on legume-rhizobia and yucca-moth mutualisms are consistent with PFF and not with HS. Thus, in systems considered to be textbook cases of HS, we find poor support for the theory that hosts have evolved to punish cheating symbionts; instead, we show that even horizontally transmitted mutualisms can be stabilized via PFF. PFF theory may place previously underappreciated constraints on the evolution of mutualism and explain why punishment is far from ubiquitous in nature.

  19. Economic contract theory tests models of mutualism

    PubMed Central

    Weyl, E. Glen; Frederickson, Megan E.; Yu, Douglas W.; Pierce, Naomi E.

    2010-01-01

    Although mutualisms are common in all ecological communities and have played key roles in the diversification of life, our current understanding of the evolution of cooperation applies mostly to social behavior within a species. A central question is whether mutualisms persist because hosts have evolved costly punishment of cheaters. Here, we use the economic theory of employment contracts to formulate and distinguish between two mechanisms that have been proposed to prevent cheating in host–symbiont mutualisms, partner fidelity feedback (PFF) and host sanctions (HS). Under PFF, positive feedback between host fitness and symbiont fitness is sufficient to prevent cheating; in contrast, HS posits the necessity of costly punishment to maintain mutualism. A coevolutionary model of mutualism finds that HS are unlikely to evolve de novo, and published data on legume–rhizobia and yucca–moth mutualisms are consistent with PFF and not with HS. Thus, in systems considered to be textbook cases of HS, we find poor support for the theory that hosts have evolved to punish cheating symbionts; instead, we show that even horizontally transmitted mutualisms can be stabilized via PFF. PFF theory may place previously underappreciated constraints on the evolution of mutualism and explain why punishment is far from ubiquitous in nature. PMID:20733067

  20. Using vehicle-to-grid technology for frequency regulation and peak-load reduction

    NASA Astrophysics Data System (ADS)

    White, Corey D.; Zhang, K. Max

    This paper explores the potential financial return for using plug-in hybrid electric vehicles as a grid resource. While there is little financial incentive for individuals when the vehicle-to-grid (V2G) service is used exclusively for peak reduction, there is a significant potential for financial return when the V2G service is used for frequency regulation. We propose that these two uses for V2G technology are not mutually exclusive, and that there could exist a "dual-use" program that utilizes V2G for multiple uses simultaneously. In our proposition, V2G could be used for regulation on a daily basis to ensure profits, and be used for peak reduction on days with high electricity demand and poor ambient air quality in order to reap the greatest environmental benefits. The profits for the individual in this type of dual-use program are close to or even higher than the profits experienced in either of the single-use programs. More importantly, we argue that the external benefits of this type of program are much greater as well. At higher V2G participation rates, our analysis shows that the market for regulation capacity could become saturated by V2G-based regulation providers. At the same time, there is plenty of potential for widespread use of V2G technology, especially if the demand for regulation, reserves, and storage grows as more intermittent renewable resources are being incorporated into the power systems.

  1. A Hamiltonian driven quantum-like model for overdistribution in episodic memory recollection.

    NASA Astrophysics Data System (ADS)

    Broekaert, Jan B.; Busemeyer, Jerome R.

    2017-06-01

    While people famously forget genuine memories over time, they also tend to mistakenly over-recall equivalent memories concerning a given event. The memory phenomenon is known by the name of episodic overdistribution and occurs both in memories of disjunctions and partitions of mutually exclusive events and has been tested, modeled and documented in the literature. The total classical probability of recalling exclusive sub-events most often exceeds the probability of recalling the composed event, i.e. a subadditive total. We present a Hamiltonian driven propagation for the Quantum Episodic Memory model developed by Brainerd (et al., 2015) for the episodic memory overdistribution in the experimental immediate item false memory paradigm (Brainerd and Reyna, 2008, 2010, 2015). Following the Hamiltonian method of Busemeyer and Bruza (2012) our model adds time-evolution of the perceived memory state through the stages of the experimental process based on psychologically interpretable parameters - γ_c for recollection capability of cues, κ_p for bias or description-dependence by probes and β for the average gist component in the memory state at start. With seven parameters the Hamiltonian model shows good accuracy of predictions both in the EOD-disjunction and in the EOD-subadditivity paradigm. We noticed either an outspoken preponderance of the gist over verbatim trace, or the opposite, in the initial memory state when β is real. Only for complex β a mix of both traces is present in the initial state for the EOD-subadditivity paradigm.

  2. Mutual proximity graphs for improved reachability in music recommendation.

    PubMed

    Flexer, Arthur; Stevens, Jeff

    2018-01-01

    This paper is concerned with the impact of hubness, a general problem of machine learning in high-dimensional spaces, on a real-world music recommendation system based on visualisation of a k-nearest neighbour (knn) graph. Due to a problem of measuring distances in high dimensions, hub objects are recommended over and over again while anti-hubs are nonexistent in recommendation lists, resulting in poor reachability of the music catalogue. We present mutual proximity graphs, which are an alternative to knn and mutual knn graphs, and are able to avoid hub vertices having abnormally high connectivity. We show that mutual proximity graphs yield much better graph connectivity resulting in improved reachability compared to knn graphs, mutual knn graphs and mutual knn graphs enhanced with minimum spanning trees, while simultaneously reducing the negative effects of hubness.

  3. Mutual proximity graphs for improved reachability in music recommendation

    PubMed Central

    Flexer, Arthur; Stevens, Jeff

    2018-01-01

    This paper is concerned with the impact of hubness, a general problem of machine learning in high-dimensional spaces, on a real-world music recommendation system based on visualisation of a k-nearest neighbour (knn) graph. Due to a problem of measuring distances in high dimensions, hub objects are recommended over and over again while anti-hubs are nonexistent in recommendation lists, resulting in poor reachability of the music catalogue. We present mutual proximity graphs, which are an alternative to knn and mutual knn graphs, and are able to avoid hub vertices having abnormally high connectivity. We show that mutual proximity graphs yield much better graph connectivity resulting in improved reachability compared to knn graphs, mutual knn graphs and mutual knn graphs enhanced with minimum spanning trees, while simultaneously reducing the negative effects of hubness. PMID:29348779

  4. Mutual information against correlations in binary communication channels.

    PubMed

    Pregowska, Agnieszka; Szczepanski, Janusz; Wajnryb, Eligiusz

    2015-05-19

    Explaining how the brain processing is so fast remains an open problem (van Hemmen JL, Sejnowski T., 2004). Thus, the analysis of neural transmission (Shannon CE, Weaver W., 1963) processes basically focuses on searching for effective encoding and decoding schemes. According to the Shannon fundamental theorem, mutual information plays a crucial role in characterizing the efficiency of communication channels. It is well known that this efficiency is determined by the channel capacity that is already the maximal mutual information between input and output signals. On the other hand, intuitively speaking, when input and output signals are more correlated, the transmission should be more efficient. A natural question arises about the relation between mutual information and correlation. We analyze the relation between these quantities using the binary representation of signals, which is the most common approach taken in studying neuronal processes of the brain. We present binary communication channels for which mutual information and correlation coefficients behave differently both quantitatively and qualitatively. Despite this difference in behavior, we show that the noncorrelation of binary signals implies their independence, in contrast to the case for general types of signals. Our research shows that the mutual information cannot be replaced by sheer correlations. Our results indicate that neuronal encoding has more complicated nature which cannot be captured by straightforward correlations between input and output signals once the mutual information takes into account the structure and patterns of the signals.

  5. No Evidence of Emotional Dysregulation or Aversion to Mutual Gaze in Preschoolers with Autism Spectrum Disorder: An Eye-Tracking Pupillometry Study

    ERIC Educational Resources Information Center

    Nuske, Heather J.; Vivanti, Giacomo; Dissanayake, Cheryl

    2015-01-01

    The "gaze aversion hypothesis", suggests that people with Autism Spectrum Disorder (ASD) avoid mutual gaze because they experience it as hyper-arousing. To test this hypothesis we showed mutual and averted gaze stimuli to 23 mixed-ability preschoolers with ASD ("M" Mullen DQ = 68) and 21 typically-developing preschoolers, aged…

  6. The interaction of HMGB1 and linker histones occurs through their acidic and basic tails.

    PubMed

    Cato, Laura; Stott, Katherine; Watson, Matthew; Thomas, Jean O

    2008-12-31

    H1 and HMGB1 bind to linker DNA in chromatin, in the vicinity of the nucleosome dyad. They appear to have opposing effects on the nucleosome, H1 stabilising it by "sealing" two turns of DNA around the octamer, and HMGB1 destabilising it, probably by bending the adjacent DNA. Their presence in chromatin might be mutually exclusive. Displacement/replacement of one by the other as a result of their highly dynamic binding in vivo might, in principle, involve interactions between them. Chemical cross-linking and gel-filtration show that a 1:1 linker histone/HMGB1 complex is formed, which persists at physiological ionic strength, and that complex formation requires the acidic tail of HMGB1. NMR spectroscopy shows that the linker histone binds, predominantly through its basic C-terminal domain, to the acidic tail of HMGB1, thereby disrupting the interaction of the tail with the DNA-binding faces of the HMG boxes. A potential consequence of this interaction is enhanced DNA binding by HMGB1, and concomitantly lowered affinity of H1 for DNA. In a chromatin context, this might facilitate displacement of H1 by HMGB1.

  7. Expansion and concatenation of nonmuscle myosin IIA filaments drive cellular contractile system formation during interphase and mitosis

    PubMed Central

    Fenix, Aidan M.; Taneja, Nilay; Buttler, Carmen A.; Lewis, John; Van Engelenburg, Schuyler B.; Ohi, Ryoma; Burnette, Dylan T.

    2016-01-01

    Cell movement and cytokinesis are facilitated by contractile forces generated by the molecular motor, nonmuscle myosin II (NMII). NMII molecules form a filament (NMII-F) through interactions of their C-terminal rod domains, positioning groups of N-terminal motor domains on opposite sides. The NMII motors then bind and pull actin filaments toward the NMII-F, thus driving contraction. Inside of crawling cells, NMIIA-Fs form large macromolecular ensembles (i.e., NMIIA-F stacks), but how this occurs is unknown. Here we show NMIIA-F stacks are formed through two non–mutually exclusive mechanisms: expansion and concatenation. During expansion, NMIIA molecules within the NMIIA-F spread out concurrent with addition of new NMIIA molecules. Concatenation occurs when multiple NMIIA-Fs/NMIIA-F stacks move together and align. We found that NMIIA-F stack formation was regulated by both motor activity and the availability of surrounding actin filaments. Furthermore, our data showed expansion and concatenation also formed the contractile ring in dividing cells. Thus interphase and mitotic cells share similar mechanisms for creating large contractile units, and these are likely to underlie how other myosin II–based contractile systems are assembled. PMID:26960797

  8. Active and Repressive Chromatin Are Interspersed without Spreading in an Imprinted Gene Cluster in the Mammalian Genome

    PubMed Central

    Regha, Kakkad; Sloane, Mathew A.; Huang, Ru; Pauler, Florian M.; Warczok, Katarzyna E.; Melikant, Balázs; Radolf, Martin; Martens, Joost H.A.; Schotta, Gunnar; Jenuwein, Thomas; Barlow, Denise P.

    2010-01-01

    SUMMARY The Igf2r imprinted cluster is an epigenetic silencing model in which expression of a ncRNA silences multiple genes in cis. Here, we map a 250 kb region in mouse embryonic fibroblast cells to show that histone modifications associated with expressed and silent genes are mutually exclusive and localized to discrete regions. Expressed genes were modified at promoter regions by H3K4me3 + H3K4me2 + H3K9Ac and on putative regulatory elements flanking active promoters by H3K4me2 + H3K9Ac. Silent genes showed two types of nonoverlapping profile. One type spread over large domains of tissue-specific silent genes and contained H3K27me3 alone. A second type formed localized foci on silent imprinted gene promoters and a nonexpressed pseudogene and contained H3K9me3 + H4K20me3 ± HP1. Thus, mammalian chromosome arms contain active chromatin interspersed with repressive chromatin resembling the type of heterochromatin previously considered a feature of centromeres, telomeres, and the inactive X chromosome. PMID:17679087

  9. In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse

    PubMed Central

    Morselli, Marco; Pastor, William A; Montanini, Barbara; Nee, Kevin; Ferrari, Roberto; Fu, Kai; Bonora, Giancarlo; Rubbi, Liudmilla; Clark, Amander T; Ottonello, Simone; Jacobsen, Steven E; Pellegrini, Matteo

    2015-01-01

    Methylation of cytosines (5meC) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5meC levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo. DOI: http://dx.doi.org/10.7554/eLife.06205.001 PMID:25848745

  10. Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA.

    PubMed

    Xu, Bin; Pizarro, Juan C; Holmes, Margaret A; McBeth, Christine; Groh, Veronika; Spies, Thomas; Strong, Roland K

    2011-02-08

    γδ T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human γδ T cells of the V(δ)1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V(δ)1 γδ T-cell receptor (TCR) showed expected overall structural homology to antibodies, αβ, and other γδ TCRs, but complementary determining region conformations and conservation of V(δ)1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on γδ T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of γδ T-cell/target cell interfaces.

  11. The Second Law and Quantum Physics

    NASA Astrophysics Data System (ADS)

    Bennett, Charles H.

    2008-08-01

    In this talk, I discuss the mystery of the second law and its relation to quantum information. There are many explanations of the second law, mostly satisfactory and not mutually exclusive. Here, I advocate quantum mechanics and quantum information as something that, through entanglement, helps resolve the paradox or the puzzle of the origin of the second law. I will discuss the interpretation called quantum Darwinism and how it helps explain why our world seems so classical, and what it has to say about the permanence or transience of information. And I will discuss a simple model illustrating why systems away from thermal equilibrium tend to be more complicated.

  12. Caring for people with AIDS: nurses' attitudes and feelings.

    PubMed

    Breault, A J; Polifroni, E C

    1992-01-01

    A qualitative, non-experimental study was conducted to identify the feelings and attitudes that nurses associate with caring for people with AIDS. Data collection and analysis were guided by the phenomenological method. Cognitive dissonance theory served as the theoretical framework to view the experience of caring for someone with AIDS. Data analysis of audiotaped, semi-structured interviews resulted in the identification of six mutually inclusive as well as exclusive themes which represent the attitudes and feelings of nurses: fear, anger, sympathy, self-enhancement, fatigue and helplessness. Particularly evident were differences in the way respondents perceived and treated AIDS patients who are intravenous drug users and those who are homosexuals.

  13. Stress Management in Cyst-Forming Free-Living Protists: Programmed Cell Death and/or Encystment

    PubMed Central

    Khan, Naveed Ahmed; Iqbal, Junaid

    2015-01-01

    In the face of harsh conditions and given a choice, a cell may (i) undergo programmed cell death, (ii) transform into a cancer cell, or (iii) enclose itself into a cyst form. In metazoans, the available evidence suggests that cellular machinery exists only to execute or avoid programmed cell death, while the ability to form a cyst was either lost or never developed. For cyst-forming free-living protists, here we pose the question whether the ability to encyst was gained at the expense of the programmed cell death or both functions coexist to counter unfavorable environmental conditions with mutually exclusive phenotypes. PMID:25648302

  14. Inventing and improving ribozyme function: rational design versus iterative selection methods

    NASA Technical Reports Server (NTRS)

    Breaker, R. R.; Joyce, G. F.

    1994-01-01

    Two major strategies for generating novel biological catalysts exist. One relies on our knowledge of biopolymer structure and function to aid in the 'rational design' of new enzymes. The other, often called 'irrational design', aims to generate new catalysts, in the absence of detailed physicochemical knowledge, by using selection methods to search a library of molecules for functional variants. Both strategies have been applied, with considerable success, to the remodeling of existing ribozymes and the development of ribozymes with novel catalytic function. The two strategies are by no means mutually exclusive, and are best applied in a complementary fashion to obtain ribozymes with the desired catalytic properties.

  15. Ion microscopy with resonant ionization mass spectrometry : time-of-flight depth profiling with improved isotopic precision.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pellin, M. J.; Veryovkin, I. V.; Levine, J.

    2010-01-01

    There are four generally mutually exclusive requirements that plague many mass spectrometric measurements of trace constituents: (1) the small size (limited by the depth probed) of many interesting materials requires high useful yields to simply detect some trace elements, (2) the low concentrations of interesting elements require efficient discrimination from isobaric interferences, (3) it is often necessary to measure the depth distribution of elements with high surface and low bulk contributions, and (4) many applications require precise isotopic analysis. Resonant ionization mass spectrometry has made dramatic progress in addressing these difficulties over the past five years.

  16. When selves have sex: what the phenomenology of trans sexuality can teach about sexual orientation.

    PubMed

    Bettcher, Talia Mae

    2014-01-01

    In this article, Bettcher argues that sexual attraction must be reconceptualized in light of transgender experience. In particular, Bettcher defends the theory of "erotic structuralism," which replaces an exclusively other-directed account of gendered attraction with one that includes a gendered eroticization of self as an essential component. This erotic experience of self is necessary for other-directed gendered desire, where the two are bound together and mutually informing. One consequence of the theory is that the controversial notion of "autogynephilia" is rejected. Another consequence is that the distinction between gender identity and sexual orientation is softened.

  17. Nature of phosphorus limitation in the ultraoligotrophic eastern Mediterranean.

    PubMed

    Thingstad, T F; Krom, M D; Mantoura, R F C; Flaten, G A F; Groom, S; Herut, B; Kress, N; Law, C S; Pasternak, A; Pitta, P; Psarra, S; Rassoulzadegan, F; Tanaka, T; Tselepides, A; Wassmann, P; Woodward, E M S; Riser, C Wexels; Zodiatis, G; Zohary, T

    2005-08-12

    Phosphate addition to surface waters of the ultraoligotrophic, phosphorus-starved eastern Mediterranean in a Lagrangian experiment caused unexpected ecosystem responses. The system exhibited a decline in chlorophyll and an increase in bacterial production and copepod egg abundance. Although nitrogen and phosphorus colimitation hindered phytoplankton growth, phosphorous may have been transferred through the microbial food web to copepods via two, not mutually exclusive, pathways: (i) bypass of the phytoplankton compartment by phosphorus uptake in heterotrophic bacteria and (ii) tunnelling, whereby phosphate luxury consumption rapidly shifts the stoichiometric composition of copepod prey. Copepods may thus be coupled to lower trophic levels through interactions not usually considered.

  18. Nature of Phosphorus Limitation in the Ultraoligotrophic Eastern Mediterranean

    NASA Astrophysics Data System (ADS)

    Thingstad, T. F.; Krom, M. D.; Mantoura, R. F. C.; Flaten, G. A. F.; Groom, S.; Herut, B.; Kress, N.; Law, C. S.; Pasternak, A.; Pitta, P.; Psarra, S.; Rassoulzadegan, F.; Tanaka, T.; Tselepides, A.; Wassmann, P.; Woodward, E. M. S.; Riser, C. Wexels; Zodiatis, G.; Zohary, T.

    2005-08-01

    Phosphate addition to surface waters of the ultraoligotrophic, phosphorus-starved eastern Mediterranean in a Lagrangian experiment caused unexpected ecosystem responses. The system exhibited a decline in chlorophyll and an increase in bacterial production and copepod egg abundance. Although nitrogen and phosphorus colimitation hindered phytoplankton growth, phosphorous may have been transferred through the microbial food web to copepods via two, not mutually exclusive, pathways: (i) bypass of the phytoplankton compartment by phosphorus uptake in heterotrophic bacteria and (ii) tunnelling, whereby phosphate luxury consumption rapidly shifts the stoichiometric composition of copepod prey. Copepods may thus be coupled to lower trophic levels through interactions not usually considered.

  19. Towards Reconciliation of Several Dualities in Physician Leadership

    PubMed Central

    Walker, Keith; Kraines, Gerry

    2015-01-01

    Leadership has a renewed focus in healthcare, and physicians are being increasingly involved in a range of leadership roles. The aim of this paper is to discuss several dualities that exert tensions at the systems and individual levels. Although oppositional, the common dualities of physician leadership are not mutually exclusive but represent a complex, dynamic and interdependent relationship, often coexisting with each other and exerting tensions in multiple dimensions. The authors contend that a dialectic understanding – instead of either/or or finding a middle ground – of the opposite poles of these dualities allows for generating meaningful leadership perspectives and choices. PMID:25947031

  20. Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma

    PubMed Central

    Cooke, Susanna L; Ng, Charlotte KY; Melnyk, Nataliya; Garcia, Maria J; Hardcastle, Tom; Temple, Jillian; Langdon, Simon; Huntsman, David; Brenton, James D

    2010-01-01

    Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either due to outgrowth of an intrinsically resistant sub-clone, or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6, PEA1 and PEA2, and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and SNP array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different timepoints in the same individual. This implies that platinum sensitive and resistant disease was not linearly related but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment. PMID:20581869

  1. Mutualisms and Population Regulation: Mechanism Matters

    PubMed Central

    Jha, Shalene; Allen, David; Liere, Heidi; Perfecto, Ivette; Vandermeer, John

    2012-01-01

    For both applied and theoretical ecological science, the mutualism between ants and their hemipteran partners is iconic. In this well-studied interaction, ants are assumed to provide hemipterans protection from natural enemies in exchange for nutritive honeydew. Despite decades of research and the potential importance in pest control, the precise mechanism producing this mutualism remains contested. By analyzing maximum likelihood parameter estimates of a hemipteran population model, we show that the mechanism of the mutualism is direct, via improved hemipteran growth rates, as opposed to the frequently assumed indirect mechanism, via harassment of the specialist parasites and predators of the hemipterans. Broadly, this study demonstrates that the management of mutualism-based ecosystem services requires a mechanistic understanding of mutualistic interactions. A consequence of this finding is the counter intuitive demonstration that preserving ant participation in the ant-hemipteran mutualism may be the best way of insuring pest control. PMID:22927978

  2. Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

    PubMed

    Tomlins, Scott A; Alshalalfa, Mohammed; Davicioni, Elai; Erho, Nicholas; Yousefi, Kasra; Zhao, Shuang; Haddad, Zaid; Den, Robert B; Dicker, Adam P; Trock, Bruce J; DeMarzo, Angelo M; Ross, Ashley E; Schaeffer, Edward M; Klein, Eric A; Magi-Galluzzi, Cristina; Karnes, R Jeffrey; Jenkins, Robert B; Feng, Felix Y

    2015-10-01

    Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason scores and were more frequent in Black/African American patients (p<0.001). Clinical outcomes were not significantly different among subtypes. A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns. Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  3. Reducing Interpolation Artifacts for Mutual Information Based Image Registration

    PubMed Central

    Soleimani, H.; Khosravifard, M.A.

    2011-01-01

    Medical image registration methods which use mutual information as similarity measure have been improved in recent decades. Mutual Information is a basic concept of Information theory which indicates the dependency of two random variables (or two images). In order to evaluate the mutual information of two images their joint probability distribution is required. Several interpolation methods, such as Partial Volume (PV) and bilinear, are used to estimate joint probability distribution. Both of these two methods yield some artifacts on mutual information function. Partial Volume-Hanning window (PVH) and Generalized Partial Volume (GPV) methods are introduced to remove such artifacts. In this paper we show that the acceptable performance of these methods is not due to their kernel function. It's because of the number of pixels which incorporate in interpolation. Since using more pixels requires more complex and time consuming interpolation process, we propose a new interpolation method which uses only four pixels (the same as PV and bilinear interpolations) and removes most of the artifacts. Experimental results of the registration of Computed Tomography (CT) images show superiority of the proposed scheme. PMID:22606673

  4. Mutual information and spontaneous symmetry breaking

    NASA Astrophysics Data System (ADS)

    Hamma, A.; Giampaolo, S. M.; Illuminati, F.

    2016-01-01

    We show that the metastable, symmetry-breaking ground states of quantum many-body Hamiltonians have vanishing quantum mutual information between macroscopically separated regions and are thus the most classical ones among all possible quantum ground states. This statement is obvious only when the symmetry-breaking ground states are simple product states, e.g., at the factorization point. On the other hand, symmetry-breaking states are in general entangled along the entire ordered phase, and to show that they actually feature the least macroscopic correlations compared to their symmetric superpositions is highly nontrivial. We prove this result in general, by considering the quantum mutual information based on the two-Rényi entanglement entropy and using a locality result stemming from quasiadiabatic continuation. Moreover, in the paradigmatic case of the exactly solvable one-dimensional quantum X Y model, we further verify the general result by considering also the quantum mutual information based on the von Neumann entanglement entropy.

  5. Graph-state formalism for mutually unbiased bases

    NASA Astrophysics Data System (ADS)

    Spengler, Christoph; Kraus, Barbara

    2013-11-01

    A pair of orthonormal bases is called mutually unbiased if all mutual overlaps between any element of one basis and an arbitrary element of the other basis coincide. In case the dimension, d, of the considered Hilbert space is a power of a prime number, complete sets of d+1 mutually unbiased bases (MUBs) exist. Here we present a method based on the graph-state formalism to construct such sets of MUBs. We show that for n p-level systems, with p being prime, one particular graph suffices to easily construct a set of pn+1 MUBs. In fact, we show that a single n-dimensional vector, which is associated with this graph, can be used to generate a complete set of MUBs and demonstrate that this vector can be easily determined. Finally, we discuss some advantages of our formalism regarding the analysis of entanglement structures in MUBs, as well as experimental realizations.

  6. Ancient host specificity within a single species of brood parasitic bird

    PubMed Central

    Spottiswoode, Claire N.; Stryjewski, Katherine Faust; Quader, Suhel; Colebrook-Robjent, John F. R.; Sorenson, Michael D.

    2011-01-01

    Parasites that exploit multiple hosts often experience diversifying selection for host-specific adaptations. This can result in multiple strains of host specialists coexisting within a single parasitic species. A long-standing conundrum is how such sympatric host races can be maintained within a single parasitic species in the face of interbreeding among conspecifics specializing on different hosts. Striking examples are seen in certain avian brood parasites such as cuckoos, many of which show host-specific differentiation in traits such as host egg mimicry. Exploiting a Zambian egg collection amassed over several decades and supplemented by recent fieldwork, we show that the brood parasitic Greater Honeyguide Indicator indicator exhibits host-specific differentiation in both egg size and egg shape. Genetic analysis of honeyguide eggs and chicks show that two highly divergent mitochondrial DNA lineages are associated with ground- and tree-nesting hosts, respectively, indicating perfect fidelity to two mutually exclusive sets of host species for millions of years. Despite their age and apparent adaptive diversification, however, these ancient lineages are not cryptic species; a complete lack of differentiation in nuclear genes shows that mating between individuals reared by different hosts is sufficiently frequent to prevent speciation. These results indicate that host specificity is maternally inherited, that host-specific adaptation among conspecifics can be maintained without reproductive isolation, and that host specificity can be remarkably ancient in evolutionary terms. PMID:21949391

  7. Reconfiguration of the small intestine and diabetes remitting effects of Roux-en-Y gastric bypass surgery.

    PubMed

    Docherty, Neil G; le Roux, Carel W

    2016-03-01

    Alterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field. Augmented incretin and diminished anti-incretin effects postsurgery are explored and a model proposed that reconciles the hindgut and foregut hypotheses of improved glycaemic control as being complementary rather than mutually exclusive. Synthesis of recent findings on postbypass changes in intestinal glucose handling then follows. Finally an updated view of the role of distal bile diversion and changes in the microbiota on enteroendocrine signalling is presented. A series of nonmutually exclusive changes in small intestinal physiology likely make a significant contribution to improved glycaemic control postgastric bypass. Longitudinal data indicate that these effects do not translate into a long-term cure. A number of surgery-induced changes, however, are amenable to device-based and pharmacology-based mimicry, and this is an area for prioritization of future research focus.

  8. Interpreting psychoanalytic interpretation: a fourfold perspective.

    PubMed

    Schermer, Victor L

    2011-12-01

    Following an overview of psychoanalytic interpretation in theory, practice, and historical context, as well as the question of whether interpretations have scientific validity, the author holds that hermeneutics, the philosophical and psychological study of interpretation, provides a rich understanding of recent developments in self psychology, inter-subjective and relational perspectives, attachment theory, and psycho-spiritual views on psychoanalytic process. He then offers four distinct hermeneutical vantage points regarding interpretation in the psychoanalytic context, including (1) Freud's adaptation of the Aristotelian view of interpretation as the uncovering of a set of predetermined meanings and structures; (2) the phenomenological view of interpretation as the laying bare of "the things themselves," that is, removing the coverings of objectification and concretization imposed by social norms and the conscious ego; (3) the dialogical existential view of interpretation as an ongoing relational process; and (4) the transformational understanding in which interpretation evokes a "presence" that transforms both patient and analyst. He concludes by contending that these perspectives are not mutually exclusive ways of conducting an analysis, but rather that all occur within the analyst's suspended attention, the caregiving and holding essential to good therapeutic outcomes, and the mutuality of the psychoanalytic dialogue.

  9. Opioid inhibition of N-type Ca2+ channels and spinal analgesia couple to alternative splicing.

    PubMed

    Andrade, Arturo; Denome, Sylvia; Jiang, Yu-Qiu; Marangoudakis, Spiro; Lipscombe, Diane

    2010-10-01

    Alternative pre-mRNA splicing occurs extensively in the nervous systems of complex organisms, including humans, considerably expanding the potential size of the proteome. Cell-specific alternative pre-mRNA splicing is thought to optimize protein function for specialized cellular tasks, but direct evidence for this is limited. Transmission of noxious thermal stimuli relies on the activity of N-type Ca(V)2.2 calcium channels in nociceptors. Using an exon-replacement strategy in mice, we show that mutually exclusive splicing patterns in the Ca(V)2.2 gene modulate N-type channel function in nociceptors, leading to a change in morphine analgesia. Exon 37a (e37a) enhances μ-opioid receptor-mediated inhibition of N-type calcium channels by promoting activity-independent inhibition. In the absence of e37a, spinal morphine analgesia is weakened in vivo but the basal response to noxious thermal stimuli is not altered. Our data suggest that highly specialized, discrete cellular responsiveness in vivo can be attributed to alternative splicing events regulated at the level of individual neurons.

  10. The latency complex: the dead hand of anti-development.

    PubMed

    Proner, Barry D

    2017-09-01

    It is common knowledge that the same phenomena can be viewed in a variety of ways. This paper considers the implications of a constellation observed in some adult patients who have increasingly reminded the author of some of the children of latency age with whom he has also worked. In the literature these patients may also have been thought about in terms of 'defences of the self' (Fordham), patients who are 'difficult to reach' (Joseph), 'psychic retreats' (Steiner), and those who make 'attacks on linking' (Bion). They may equally be considered in terms of schizoid, narcissistic or borderline personalities, or as showing features on the autistic spectrum, such as mindlessness and extreme obsessionality. Writers such as Helene Deutsch with her concept of an 'as-if personality', Winnicott with his 'false self', and Rosenfeld, discussing the split-off parts of the personality in narcissistic patients, have also offered much to think about in their consideration of some of these phenomena. This paper proposes yet another vertex - the author's own imaginative conjecture - that is by no means mutually exclusive of any of these others. © 2017, The Society of Analytical Psychology.

  11. Attitudes Toward Addiction, Methadone Treatment, and Recovery Among HIV-Infected Ukrainian Prisoners Who Inject Drugs: Incarceration Effects and Exploration of Mediators.

    PubMed

    Polonsky, Maxim; Rozanova, Julia; Azbel, Lyuba; Bachireddy, Chethan; Izenberg, Jacob; Kiriazova, Tetiana; Dvoryak, Sergii; Altice, Frederick L

    2016-12-01

    In this study, we use data from a survey conducted in Ukraine among 196 HIV-infected people who inject drugs, to explore attitudes toward drug addiction and methadone maintenance therapy (MMT), and intentions to change drug use during incarceration and after release from prison. Two groups were recruited: Group 1 (n = 99) was currently incarcerated and Group 2 (n = 97) had been recently released from prison. This paper's key finding is that MMT treatment and addiction recovery were predominantly viewed as mutually exclusive processes. Group comparisons showed that participants in Group 1 (pre-release) exhibited higher optimism about changing their drug use, were less likely to endorse methadone, and reported higher intention to recover from their addiction. Group 2 participants (post-release), however, reported higher rates of HIV stigma. Structural equation modeling revealed that in both groups, optimism about recovery and awareness of addiction mediated the effect of drug addiction severity on intentions to recover from their addiction.

  12. Strengthening and toughening metallic glasses: The elastic perspectives and opportunities

    NASA Astrophysics Data System (ADS)

    Liu, Z. Q.; Zhang, Z. F.

    2014-04-01

    There exist general conflicts between strength and toughness in crystalline engineering materials, and various strengthening and toughening strategies have been developed from the dislocation motion perspectives. Metallic glasses (MGs) have demonstrated great potentials owing to their unique properties; however, their structural applications are strictly limited. One of the key problems is that the traditional strengthening and toughening strategies and mechanisms are not applicable in MGs due to the absence of dislocations and crystalline microstructures. Here, we show that the strength and toughness, or equivalently the shear modulus and Poisson's ratio, are invariably mutually exclusive in MGs. Accordingly, the MGs can be categorized into four groups with different levels of integrated mechanical properties. It is further revealed that the conflicts originate fundamentally from the atomic bonding structures and the levels of strength-toughness combinations are indeed dominated by the bulk modulus. Moreover, we propose novel strategies for optimizing the mechanical properties of MGs from the elastic perspectives. We emphasize the significance of developing high bulk modulus MGs to achieve simultaneously both high strength and good toughness and highlight the elastic opportunities for strengthening and toughening materials.

  13. The Connection Between Introversion/Extraversion and Social Capital Outcomes of Playing World of Warcraft.

    PubMed

    Reer, Felix; Krämer, Nicole C

    2017-02-01

    Some studies indicated that playing online games yields a "rich-get-richer effect" and is especially socially beneficial for extraverted players, while other authors argue that online gaming could have compensational effects for introverted players. The current survey study (N = 409) investigates the connection between introversion/extraversion and social capital outcomes of playing the popular role-playing game World of Warcraft and shows that the rich-get-richer and the compensation perspective are not mutually exclusive. Path analysis revealed that extraverted players communicated and self-disclosed more extensively, more often engaged in team play, and, hence, had better chances to build up social capital than introverts. However, at least some of the introverted players used the game for social compensation. These players chose a more social playing style, which increased their chances to acquire social capital. The results demonstrate that the group of introverted players is more heterogeneous than previously thought and that the links between personality aspects and social outcomes of playing are quite complex and rather indirect than direct.

  14. Nanoscale origins of the damage tolerance of the high-entropy alloy CrMnFeCoNi

    DOE PAGES

    Zhang, ZiJiao; Mao, M. M.; Wang, Jiangwei; ...

    2015-12-09

    Damage tolerance can be an elusive characteristic of structural materials requiring both high strength and ductility, properties that are often mutually exclusive. High-entropy alloys are of interest in this regard. Specifically, the single-phase CrMnFeCoNi alloy displays tensile strength levels of ~1 GPa, excellent ductility (~60–70%) and exceptional fracture toughness (KJIc>200M Pa√m). Here through the use of in situ straining in an aberration-corrected transmission electron microscope, we report on the salient atomistic to micro-scale mechanisms underlying the origin of these properties. We identify a synergy of multiple deformation mechanisms, rarely achieved in metallic alloys, which generates high strength, work hardening andmore » ductility, including the easy motion of Shockley partials, their interactions to form stacking-fault parallelepipeds, and arrest at planar slip bands of undissociated dislocations. In conclusion, we further show that crack propagation is impeded by twinned, nanoscale bridges that form between the near-tip crack faces and delay fracture by shielding the crack tip.« less

  15. Nanoscale origins of the damage tolerance of the high-entropy alloy CrMnFeCoNi

    PubMed Central

    Zhang, ZiJiao; Mao, M. M.; Wang, Jiangwei; Gludovatz, Bernd; Zhang, Ze; Mao, Scott X.; George, Easo P.; Yu, Qian; Ritchie, Robert O.

    2015-01-01

    Damage tolerance can be an elusive characteristic of structural materials requiring both high strength and ductility, properties that are often mutually exclusive. High-entropy alloys are of interest in this regard. Specifically, the single-phase CrMnFeCoNi alloy displays tensile strength levels of ∼1 GPa, excellent ductility (∼60–70%) and exceptional fracture toughness (KJIc>200 MPa√m). Here through the use of in situ straining in an aberration-corrected transmission electron microscope, we report on the salient atomistic to micro-scale mechanisms underlying the origin of these properties. We identify a synergy of multiple deformation mechanisms, rarely achieved in metallic alloys, which generates high strength, work hardening and ductility, including the easy motion of Shockley partials, their interactions to form stacking-fault parallelepipeds, and arrest at planar slip bands of undissociated dislocations. We further show that crack propagation is impeded by twinned, nanoscale bridges that form between the near-tip crack faces and delay fracture by shielding the crack tip. PMID:26647978

  16. The role of depression and anxiety in impulsive and obsessive-compulsive behaviors among anorexic and bulimic patients.

    PubMed

    Finzi-Dottan, Ricky; Zubery, Eynat

    2009-01-01

    Eating disorders are believed to range across a spectrum of varying degrees of obsessive-compulsive and impulsive behavior. Sixty anorexic (mean age = 19.8; sd = 5.9) and 109 bulimic (mean age = 26.9; sd = 11.3) female patients completed self-report questionnaires assessing obsessive-compulsiveness, impulsivity, depression and anxiety, as well as two eating disorder scales. Results yielded significantly higher levels of impulsivity and negative body image in the bulimic compared to the anorexic group. Regression analysis predicting impulsivity showed that bulimia and negative body image were the main contributors. Regression analysis for predicting obsessive-compulsive behavior suggested that depression and anxiety obscure the link between anorexia and obsessive-compulsive behavior, and a high BMI intensifies the association between anxiety and obsessive-compulsive behavior. The high rates of both impulsivity and obsessive-compulsiveness found in both groups, and their association with the severity of the eating disorder, may suggest that impulsivity and obsessive-compulsiveness are not mutually exclusive and can both be found among anorexic and bulimic patients.

  17. ADHD and autism: differential diagnosis or overlapping traits? A selective review.

    PubMed

    Taurines, Regina; Schwenck, Christina; Westerwald, Eva; Sachse, Michael; Siniatchkin, Michael; Freitag, Christine

    2012-09-01

    According to DSM-IV TR and ICD-10, a diagnosis of autism or Asperger Syndrome precludes a diagnosis of attention-deficit/hyperactivity disorder (ADHD). However, despite the different conceptualization, population-based twin studies reported symptom overlap, and a recent epidemiologically based study reported a high rate of ADHD in autism and autism spectrum disorders (ASD). In the planned revision of the DSM-IV TR, dsm5 (www.dsm5.org), the diagnoses of autistic disorder and ADHD will not be mutually exclusive any longer. This provides the basis of more differentiated studies on overlap and distinction between both disorders. This review presents data on comorbidity rates and symptom overlap and discusses common and disorder-specific risk factors, including recent proteomic studies. Neuropsychological findings in the areas of attention, reward processing, and social cognition are then compared between both disorders, as these cognitive abilities show overlapping as well as specific impairment for one of both disorders. In addition, selective brain imaging findings are reported. Therapeutic options are summarized, and new approaches are discussed. The review concludes with a prospectus on open questions for research and clinical practice.

  18. How Distinctive Processing Enhances Hits and Reduces False Alarms

    PubMed Central

    Hunt, R. Reed; Smith, Rebekah E.

    2015-01-01

    Distinctive processing is a concept designed to account for precision in memory, both correct responses and avoidance of errors. The principal question addressed in two experiments is how distinctive processing of studied material reduces false alarms to familiar distractors. Jacoby (Jacoby, Kelley, & McElree, 1999) has used the metaphors early selection and late correction to describe two different types of control processes. Early selection refers to limitations on access whereas late correction describes controlled monitoring of accessed information. The two types of processes are not mutually exclusive, and previous research has provided evidence for the operation of both. The data reported here extend previous work to a criterial recollection paradigm and to a recognition memory test. The results of both experiments show that variables that reduce false memory for highly familiar distracters continue to exert their effect under conditions of minimal post-access monitoring. Level of monitoring was reduced in the first experiment through test instructions and in the second experiment through speeded test responding. The results were consistent with the conclusion that both early selection and late correction operate to control accuracy in memory. PMID:26034343

  19. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

    PubMed Central

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

    2016-01-01

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

  20. Global synchronization algorithms for the Intel iPSC/860

    NASA Technical Reports Server (NTRS)

    Seidel, Steven R.; Davis, Mark A.

    1992-01-01

    In a distributed memory multicomputer that has no global clock, global processor synchronization can only be achieved through software. Global synchronization algorithms are used in tridiagonal systems solvers, CFD codes, sequence comparison algorithms, and sorting algorithms. They are also useful for event simulation, debugging, and for solving mutual exclusion problems. For the Intel iPSC/860 in particular, global synchronization can be used to ensure the most effective use of the communication network for operations such as the shift, where each processor in a one-dimensional array or ring concurrently sends a message to its right (or left) neighbor. Three global synchronization algorithms are considered for the iPSC/860: the gysnc() primitive provided by Intel, the PICL primitive sync0(), and a new recursive doubling synchronization (RDS) algorithm. The performance of these algorithms is compared to the performance predicted by communication models of both the long and forced message protocols. Measurements of the cost of shift operations preceded by global synchronization show that the RDS algorithm always synchronizes the nodes more precisely and costs only slightly more than the other two algorithms.

  1. Combined point mutation in KRAS or EGFR genes and EML4-ALK translocation in lung cancer patients.

    PubMed

    Jürgens, Jessica; Engel-Riedel, Walburga; Prickartz, Alexander; Ludwig, Corinna; Schildgen, Oliver; Tillmann, Ramona-Liza; Stoelben, Erich; Brockmann, Michael; Schildgen, Verena

    2014-03-01

    A total of three cases with novel constellations regarding mutation patterns in non-small-cell lung cancer (NSCLC) are reported. The mutation patterns that are observed are novel and unexpected. First, a combined simultaneous KRAS mutation and EML4-ALK translocation, both in the main tumor and a bone metastasis, were observed, these mutations are assumed to mutually exclude each other. A further two cases include a father and a daughter, both of whom are suffering from NSCLC with different EGFR mutation patterns. A common cause was assumed; however, could not be deduced to mutations in the KRAS, BRAF and EGFR genes. The aforementioned cases are important, as it must be taken into account that mutations previously assumed to be exclusive can occur in combination, may influence the clinical outcome and may require different therapy compared with single mutated tumors. It has to be discussed whether diagnostic algorithms need to be adapted. The cases of father and daughter show that further unknown factors can influence development of NSCLC.

  2. Auditory rhythmic cueing in movement rehabilitation: findings and possible mechanisms

    PubMed Central

    Schaefer, Rebecca S.

    2014-01-01

    Moving to music is intuitive and spontaneous, and music is widely used to support movement, most commonly during exercise. Auditory cues are increasingly also used in the rehabilitation of disordered movement, by aligning actions to sounds such as a metronome or music. Here, the effect of rhythmic auditory cueing on movement is discussed and representative findings of cued movement rehabilitation are considered for several movement disorders, specifically post-stroke motor impairment, Parkinson's disease and Huntington's disease. There are multiple explanations for the efficacy of cued movement practice. Potentially relevant, non-mutually exclusive mechanisms include the acceleration of learning; qualitatively different motor learning owing to an auditory context; effects of increased temporal skills through rhythmic practices and motivational aspects of musical rhythm. Further considerations of rehabilitation paradigm efficacy focus on specific movement disorders, intervention methods and complexity of the auditory cues. Although clinical interventions using rhythmic auditory cueing do not show consistently positive results, it is argued that internal mechanisms of temporal prediction and tracking are crucial, and further research may inform rehabilitation practice to increase intervention efficacy. PMID:25385780

  3. Private channels in plant-pollinator mutualisms

    PubMed Central

    Chen, Chun; Hossaert-McKey, Martine

    2010-01-01

    Volatile compounds often mediate plant-pollinator interactions, and may promote specialization in plant-pollinator relationships, notably through private channels of unusual compounds. Nevertheless, the existence of private channels, i.e., the potential for exclusive communication via unique signals and receptors, is still debated in the literature. Interactions between figs and their pollinating wasps offer opportunities for exploring this concept. Several experiments have demonstrated that chemical mediation is crucial in ensuring the encounter between figs and their species-specific pollinators. Indeed, chemical messages emitted by figs are notably species- and developmental stage-specific, making them reliable cues for the pollinator. In most cases, the species-specificity of wasp attraction is unlikely to result from the presence of a single specific compound. Nevertheless, a recent paper on the role of scents in the interaction between Ficus semicordata and its pollinating wasp Ceratosolen gravelyi showed that a single compound, 4-methylanisole, is the main signal compound in the floral scent, and is sufficient by itself to attract the obligate pollinator. Mainly focusing on these results, we propose here that a floral scent can act as a private channel, attracting only the highly specific pollinator. PMID:20484975

  4. A DNA methylation map of human cancer at single base-pair resolution

    PubMed Central

    Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

    2017-01-01

    Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination. PMID:28581523

  5. Wingless, decapentaplegic and EGF receptor signaling pathways interact to specify dorso-ventral pattern in the adult abdomen of Drosophila.

    PubMed

    Kopp, A; Blackman, R K; Duncan, I

    1999-08-01

    Adult abdominal segments of Drosophila are subdivided along the dorso-ventral axis into a dorsal tergite, a ventral sternite and ventro-lateral pleural cuticle. We report that this pattern is largely specified during the pupal stage by Wingless (Wg), Decapentaplegic (Dpp) and Drosophila EGF Receptor (DER) signaling. Expression of wg and dpp is activated at the posterior edge of the anterior compartment by Hedgehog signaling. Within this region, wg and dpp are expressed in domains that are mutually exclusive along the dorso-ventral axis: wg is expressed in the sternite and medio-lateral tergite, whereas dpp expression is confined to the pleura and the dorsal midline. Neither gene is expressed in the lateral tergite. Shirras and Couso (1996, Dev. Biol. 175, 24-36) have shown that tergite and sternite cell fates are specified by Wg signaling. We find that DER acts synergistically with Wg to promote tergite and sternite identities, and that Wg and DER activities are opposed by Dpp signaling, which promotes pleural identity. Wg and Dpp interact antagonistically at two levels. First, their expression is confined to complementary domains by mutual transcriptional repression. Second, Wg and Dpp compete directly with one another by exerting opposite effects on cell fate. DER signaling does not affect the expression of wg or dpp, indicating that it interacts with Wg and Dpp at the level of cell fate determination. Within the tergite, the requirements for Wg and DER function are roughly complementary: Wg is required mainly in the medial region, whereas DER is most important laterally. Finally, we show that Dpp signaling at the dorsal midline controls dorso-ventral patterning within the tergite by promoting pigmentation in the medial region.

  6. A reassessment of the taxonomic position of mesosaurs, and a surprising phylogeny of early amniotes

    NASA Astrophysics Data System (ADS)

    Laurin, Michel; Piñeiro, Graciela H.

    2017-11-01

    We reassess the phylogenetic position of mesosaurs by using a data matrix that is updated and slightly expanded from a matrix that the first author published in 1995 with his former thesis advisor. The revised matrix, which incorporates anatomical information published in the last twenty years and observations on several mesosaur specimens (mostly from Uruguay) includes seventeen terminal taxa and 129 characters (four more taxa and five more characters than the original matrix from 1995). The new matrix also differs by incorporating more ordered characters (all morphoclines were ordered). Parsimony analyses in PAUP 4 using the branch and bound algorithm show that the new matrix supports a position of mesosaurs at the very base of Sauropsida, as suggested by the first author in 1995. The exclusion of mesosaurs from a less inclusive clade of sauropsids is supported by a Bremer (Decay) index of 4 and a bootstrap frequency of 66%, both of which suggest that this result is moderately robust. The most parsimonious trees include some unexpected results, such as placing the anapsid reptile Paleothyris near the base of diapsids, and all of parareptiles as the sister-group of younginiforms (the most crownward diapsids included in the analyses). Turtles are placed among parareptiles, as the sister-group of pareiasaurs (and in diapsids, given that parareptiles are nested within diapsids). This unexpected result offers a potential solution to the long-lasting controversy about the position of turtles because previous studies viewed a position among diapsids and among parareptiles as mutually exclusive alternatives.

  7. Self-Editing: On the Relation Between behavioral and Psycholinguistic Approaches

    PubMed Central

    Kimberly Epting, L; Critchfield, Thomas S

    2006-01-01

    In Skinner's (1957) conceptual analysis, the process of self-editing is integral to the dynamic complexities of multiply determined verbal behavior, but the analysis has generated little in the way of an experimental analysis. The majority of scientific work on self-editing has taken place within linguistics and cognitive psycholinguistics. Here we compare and contrast behavioral and cognitive psycholinguistic approaches to self-editing, highlighting points of contact that can be identified despite fundamental differences in theoretical styles. We conclude that the two approaches are not mutually exclusive on all dimensions, and suggest that a consideration of cognitive psycholinguistic research may help to spur an experimental analysis of self-editing from a behavioral perspective. PMID:22478464

  8. Classification of adults with problematic internet experiences: linking internet and conventional problems from a clinical perspective.

    PubMed

    Mitchell, Kimberly J; Finkelhor, David; Becker-Blease, Kathryn A

    2007-06-01

    This article utilizes data from clinical reports of 929 adults to examine whether various problematic Internet experiences are distinctly different from or extensions of conventional problems. A TwoStep Cluster Analysis identified three mutually exclusive groups of adults, those with (1) online relationship problems and victimization; (2) online and offline problems; and (3) marital discord. Results suggest some initial support for the idea that problematic Internet experiences are often extensions of experiences and behaviors that pre-date the Internet. However, the Internet may be introducing some qualitatively new dimensions-such as an increased severity, an increased frequency, or unique dynamics-that require new responses or interventions.

  9. A novel visual hardware behavioral language

    NASA Technical Reports Server (NTRS)

    Li, Xueqin; Cheng, H. D.

    1992-01-01

    Most hardware behavioral languages just use texts to describe the behavior of the desired hardware design. This is inconvenient for VLSI designers who enjoy using the schematic approach. The proposed visual hardware behavioral language has the ability to graphically express design information using visual parallel models (blocks), visual sequential models (processes) and visual data flow graphs (which consist of primitive operational icons, control icons, and Data and Synchro links). Thus, the proposed visual hardware behavioral language can not only specify hardware concurrent and sequential functionality, but can also visually expose parallelism, sequentiality, and disjointness (mutually exclusive operations) for the hardware designers. That would make the hardware designers capture the design ideas easily and explicitly using this visual hardware behavioral language.

  10. Cloud classification from satellite data using a fuzzy sets algorithm: A polar example

    NASA Technical Reports Server (NTRS)

    Key, J. R.; Maslanik, J. A.; Barry, R. G.

    1988-01-01

    Where spatial boundaries between phenomena are diffuse, classification methods which construct mutually exclusive clusters seem inappropriate. The Fuzzy c-means (FCM) algorithm assigns each observation to all clusters, with membership values as a function of distance to the cluster center. The FCM algorithm is applied to AVHRR data for the purpose of classifying polar clouds and surfaces. Careful analysis of the fuzzy sets can provide information on which spectral channels are best suited to the classification of particular features, and can help determine likely areas of misclassification. General agreement in the resulting classes and cloud fraction was found between the FCM algorithm, a manual classification, and an unsupervised maximum likelihood classifier.

  11. Origins of the specialization for letters and numbers in ventral occipitotemporal cortex.

    PubMed

    Hannagan, Thomas; Amedi, Amir; Cohen, Laurent; Dehaene-Lambertz, Ghislaine; Dehaene, Stanislas

    2015-07-01

    Deep in the occipitotemporal cortex lie two functional regions, the visual word form area (VWFA) and the number form area (NFA), which are thought to play a special role in letter and number recognition, respectively. We review recent progress made in characterizing the origins of these symbol form areas in children or adults, sighted or blind subjects, and humans or monkeys. We propose two non-mutually-exclusive hypotheses on the origins of the VWFA and NFA: the presence of a connectivity bias, and a sensitivity to shape features. We assess the explanatory power of these hypotheses, describe their consequences, and offer several experimental tests. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Phenotypic plasticity and longevity in plants and animals: cause and effect?

    PubMed

    Borges, Renee M

    2009-10-01

    Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

  13. The Malpractice Feud

    PubMed Central

    Obayuwana, Alphonsus O.

    1981-01-01

    The propriety of an immediate resolution of the malpractice feud rests on the strong thesis that law and medicine cannot be mutually exclusive if both shall continue to remain true to their traditional pledges. The common need to serve, primarily, the human being and, secondarily, the client or patient is a sufficient basis for much compromise. It should always be remembered that if there were no life there would be no rights to defend; nor would life be worth its very name, if legal rights were nil. This paper assesses some of the basic differences between law and medicine, identifies the historical and recent events that precipitated the current malpractice feud, and offers some ameliorative measures for resolving the uneasy state. PMID:7218368

  14. Transformation based endorsement systems

    NASA Technical Reports Server (NTRS)

    Sudkamp, Thomas

    1988-01-01

    Evidential reasoning techniques classically represent support for a hypothesis by a numeric value or an evidential interval. The combination of support is performed by an arithmetic rule which often requires restrictions to be placed on the set of possibilities. These assumptions usually require the hypotheses to be exhausitive and mutually exclusive. Endorsement based classification systems represent support for the alternatives symbolically rather than numerically. A framework for constructing endorsement systems is presented in which transformations are defined to generate and update the knowledge base. The interaction of the knowledge base and transformations produces a non-monotonic reasoning system. Two endorsement based reasoning systems are presented to demonstrate the flexibility of the transformational approach for reasoning with ambiguous and inconsistent information.

  15. Spatial Mutual Information Based Hyperspectral Band Selection for Classification

    PubMed Central

    2015-01-01

    The amount of information involved in hyperspectral imaging is large. Hyperspectral band selection is a popular method for reducing dimensionality. Several information based measures such as mutual information have been proposed to reduce information redundancy among spectral bands. Unfortunately, mutual information does not take into account the spatial dependency between adjacent pixels in images thus reducing its robustness as a similarity measure. In this paper, we propose a new band selection method based on spatial mutual information. As validation criteria, a supervised classification method using support vector machine (SVM) is used. Experimental results of the classification of hyperspectral datasets show that the proposed method can achieve more accurate results. PMID:25918742

  16. Research on electricity consumption forecast based on mutual information and random forests algorithm

    NASA Astrophysics Data System (ADS)

    Shi, Jing; Shi, Yunli; Tan, Jian; Zhu, Lei; Li, Hu

    2018-02-01

    Traditional power forecasting models cannot efficiently take various factors into account, neither to identify the relation factors. In this paper, the mutual information in information theory and the artificial intelligence random forests algorithm are introduced into the medium and long-term electricity demand prediction. Mutual information can identify the high relation factors based on the value of average mutual information between a variety of variables and electricity demand, different industries may be highly associated with different variables. The random forests algorithm was used for building the different industries forecasting models according to the different correlation factors. The data of electricity consumption in Jiangsu Province is taken as a practical example, and the above methods are compared with the methods without regard to mutual information and the industries. The simulation results show that the above method is scientific, effective, and can provide higher prediction accuracy.

  17. Morphology and ultrastructure of the esophagus during the ontogeny of the spider crab Maja brachydactyla (Decapoda, Brachyura, Majidae).

    PubMed

    Castejón, Diego; Rotllant, Guiomar; Ribes, Enric; Durfort, Mercè; Guerao, Guillermo

    2018-06-01

    The esophagus of the eucrustaceans is known as a short tube that connects the mouth with the stomach but has generally received little attention by the carcinologists, especially during the larval stages. By this reason, the present study is focused on the morphology and ultrastructure of the esophagus in the brachyuran Maja brachydactyla during the larval development and adult stage. The esophagus shows internally four longitudinal folds. The simple columnar epithelium is covered by a thick cuticle. The epithelial cells of the adults are intensively interdigitated and show abundant apical mitochondria and bundles of filamentous structures. The cuticle surface has microspines and mutually exclusive pores. Three muscle layers surrounded by the connective tissue are reported: circular muscles forming a broad continuous band, longitudinal muscle bundles adjacent to the circular muscles, and dilator muscles crossing the connective tissue vertically toward the epithelium. The connective tissue has rosette glands. The esophagus of the larvae have epithelial cells with big vesicles but poorly developed interdigitations and filamentous structures, the cuticle is formed by a procuticle without differentiated exocuticle and endocuticle, the connective layer is thin and the rosette glands are absent. The observed features can be explained by his role in the swallowing of the food. © 2018 Wiley Periodicals, Inc.

  18. The Drosophila telomere-capping protein Verrocchio binds single-stranded DNA and protects telomeres from DNA damage response

    PubMed Central

    Cicconi, Alessandro; Micheli, Emanuela; Vernì, Fiammetta; Jackson, Alison; Gradilla, Ana Citlali; Cipressa, Francesca; Raimondo, Domenico; Bosso, Giuseppe; Wakefield, James G.; Ciapponi, Laura; Cenci, Giovanni; Gatti, Maurizio

    2017-01-01

    Abstract Drosophila telomeres are sequence-independent structures maintained by transposition to chromosome ends of three specialized retroelements rather than by telomerase activity. Fly telomeres are protected by the terminin complex that includes the HOAP, HipHop, Moi and Ver proteins. These are fast evolving, non-conserved proteins that localize and function exclusively at telomeres, protecting them from fusion events. We have previously suggested that terminin is the functional analogue of shelterin, the multi-protein complex that protects human telomeres. Here, we use electrophoretic mobility shift assay (EMSA) and atomic force microscopy (AFM) to show that Ver preferentially binds single-stranded DNA (ssDNA) with no sequence specificity. We also show that Moi and Ver form a complex in vivo. Although these two proteins are mutually dependent for their localization at telomeres, Moi neither binds ssDNA nor facilitates Ver binding to ssDNA. Consistent with these results, we found that Ver-depleted telomeres form RPA and γH2AX foci, like the human telomeres lacking the ssDNA-binding POT1 protein. Collectively, our findings suggest that Drosophila telomeres possess a ssDNA overhang like the other eukaryotes, and that the terminin complex is architecturally and functionally similar to shelterin. PMID:27940556

  19. Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane.

    PubMed

    Ukai, Hirofumi; Araki, Yasuhiro; Kira, Shintaro; Oikawa, Yu; May, Alexander I; Noda, Takeshi

    2018-04-01

    TORC1 is a central regulator of cell growth in response to amino acids. The role of the evolutionarily conserved Gtr/Rag pathway in the regulation of TORC1 is well-established. Recent genetic studies suggest that an additional regulatory pathway, depending on the activity of Pib2, plays a role in TORC1 activation independently of the Gtr/Rag pathway. However, the interplay between the Pib2 pathway and the Gtr/Rag pathway remains unclear. In this study, we show that Pib2 and Gtr/Ego form distinct complexes with TORC1 in a mutually exclusive manner, implying dedicated functional relationships between TORC1 and Pib2 or Gtr/Rag in response to specific amino acids. Furthermore, simultaneous depletion of Pib2 and the Gtr/Ego system abolishes TORC1 activity and completely compromises the vacuolar localization of TORC1. Thus, the amino acid-dependent activation of TORC1 is achieved through the Pib2 and Gtr/Ego pathways alone. Finally, we show that glutamine induces a dose-dependent increase in Pib2-TORC1 complex formation, and that glutamine binds directly to the Pib2 complex. These data provide strong preliminary evidence for Pib2 functioning as a putative glutamine sensor in the regulation of TORC1.

  20. Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane

    PubMed Central

    Ukai, Hirofumi; Araki, Yasuhiro; Kira, Shintaro; Oikawa, Yu; May, Alexander I.

    2018-01-01

    TORC1 is a central regulator of cell growth in response to amino acids. The role of the evolutionarily conserved Gtr/Rag pathway in the regulation of TORC1 is well-established. Recent genetic studies suggest that an additional regulatory pathway, depending on the activity of Pib2, plays a role in TORC1 activation independently of the Gtr/Rag pathway. However, the interplay between the Pib2 pathway and the Gtr/Rag pathway remains unclear. In this study, we show that Pib2 and Gtr/Ego form distinct complexes with TORC1 in a mutually exclusive manner, implying dedicated functional relationships between TORC1 and Pib2 or Gtr/Rag in response to specific amino acids. Furthermore, simultaneous depletion of Pib2 and the Gtr/Ego system abolishes TORC1 activity and completely compromises the vacuolar localization of TORC1. Thus, the amino acid-dependent activation of TORC1 is achieved through the Pib2 and Gtr/Ego pathways alone. Finally, we show that glutamine induces a dose-dependent increase in Pib2-TORC1 complex formation, and that glutamine binds directly to the Pib2 complex. These data provide strong preliminary evidence for Pib2 functioning as a putative glutamine sensor in the regulation of TORC1. PMID:29698392

  1. Evaluation of prediction capability, robustness, and sensitivity in non-linear landslide susceptibility models, Guantánamo, Cuba

    NASA Astrophysics Data System (ADS)

    Melchiorre, C.; Castellanos Abella, E. A.; van Westen, C. J.; Matteucci, M.

    2011-04-01

    This paper describes a procedure for landslide susceptibility assessment based on artificial neural networks, and focuses on the estimation of the prediction capability, robustness, and sensitivity of susceptibility models. The study is carried out in the Guantanamo Province of Cuba, where 186 landslides were mapped using photo-interpretation. Twelve conditioning factors were mapped including geomorphology, geology, soils, landuse, slope angle, slope direction, internal relief, drainage density, distance from roads and faults, rainfall intensity, and ground peak acceleration. A methodology was used that subdivided the database in 3 subsets. A training set was used for updating the weights. A validation set was used to stop the training procedure when the network started losing generalization capability, and a test set was used to calculate the performance of the network. A 10-fold cross-validation was performed in order to show that the results are repeatable. The prediction capability, the robustness analysis, and the sensitivity analysis were tested on 10 mutually exclusive datasets. The results show that by means of artificial neural networks it is possible to obtain models with high prediction capability and high robustness, and that an exploration of the effect of the individual variables is possible, even if they are considered as a black-box model.

  2. Dissociating medial frontal and posterior cingulate activity during self-reflection.

    PubMed

    Johnson, Marcia K; Raye, Carol L; Mitchell, Karen J; Touryan, Sharon R; Greene, Erich J; Nolen-Hoeksema, Susan

    2006-06-01

    Motivationally significant agendas guide perception, thought and behaviour, helping one to define a 'self' and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.

  3. Dissociating medial frontal and posterior cingulate activity during self-reflection

    PubMed Central

    Johnson, Marcia K.; Raye, Carol L.; Mitchell, Karen J.; Touryan, Sharon R.; Greene, Erich J.; Nolen-Hoeksema, Susan

    2006-01-01

    Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus. PMID:18574518

  4. Functional analysis of circadian pacemaker neurons in Drosophila melanogaster.

    PubMed

    Rieger, Dirk; Shafer, Orie Thomas; Tomioka, Kenji; Helfrich-Förster, Charlotte

    2006-03-01

    The molecular mechanisms of circadian rhythms are well known, but how multiple clocks within one organism generate a structured rhythmic output remains a mystery. Many animals show bimodal activity rhythms with morning (M) and evening (E) activity bouts. One long-standing model assumes that two mutually coupled oscillators underlie these bouts and show different sensitivities to light. Three groups of lateral neurons (LN) and three groups of dorsal neurons govern behavioral rhythmicity of Drosophila. Recent data suggest that two groups of the LN (the ventral subset of the small LN cells and the dorsal subset of LN cells) are plausible candidates for the M and E oscillator, respectively. We provide evidence that these neuronal groups respond differently to light and can be completely desynchronized from one another by constant light, leading to two activity components that free-run with different periods. As expected, a long-period component started from the E activity bout. However, a short-period component originated not exclusively from the morning peak but more prominently from the evening peak. This reveals an interesting deviation from the original Pittendrigh and Daan (1976) model and suggests that a subgroup of the ventral subset of the small LN acts as "main" oscillator controlling M and E activity bouts in Drosophila.

  5. A consumer-resource approach to the density-dependent population dynamics of mutualism.

    PubMed

    Holland, J Nathaniel; DeAngelis, Donald L

    2010-05-01

    Like predation and competition, mutualism is now recognized as a consumer-resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant-mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

  6. A consumer-resource approach to the density-dependent population dynamics of mutualism

    USGS Publications Warehouse

    Holland, J. Nathaniel; DeAngelis, Donald L.

    2010-01-01

    Like predation and competition, mutualism is now recognized as a consumer resource (C-R) interaction, including, in particular, bi-directional (e.g., coral, plant- mycorrhizae) and uni-directional (e.g., ant-plant defense, plant-pollinator) C-R mutualisms. Here, we develop general theory for the density-dependent population dynamics of mutualism based on the C-R mechanism of interspecific interaction. To test the influence of C-R interactions on the dynamics and stability of bi- and uni-directional C-R mutualisms, we developed simple models that link consumer functional response of one mutualistic species with the resources supplied by another. Phase-plane analyses show that the ecological dynamics of C-R mutualisms are stable in general. Most transient behavior leads to an equilibrium of mutualistic coexistence, at which both species densities are greater than in the absence of interactions. However, due to the basic nature of C-R interactions, certain density-dependent conditions can lead to C-R dynamics characteristic of predator-prey interactions, in which one species overexploits and causes the other to go extinct. Consistent with empirical phenomena, these results suggest that the C-R interaction can provide a broad mechanism for understanding density-dependent population dynamics of mutualism. By unifying predation, competition, and mutualism under the common ecological framework of consumer-resource theory, we may also gain a better understanding of the universal features of interspecific interactions in general.

  7. Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

    PubMed

    Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

    2000-07-01

    Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

  8. Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism.

    PubMed

    Zhang, H; Hu, G; Wang, H; Sciavolino, P; Iler, N; Shen, M M; Abate-Shen, C

    1997-05-01

    Protein-protein interactions are known to be essential for specifying the transcriptional activities of homeoproteins. Here we show that representative members of the Msx and Dlx homeoprotein families form homo- and heterodimeric complexes. We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. In particular, we show that Msx and Dlx proteins interact independently and noncooperatively with homeodomain DNA binding sites and that dimerization is specifically blocked by the presence of such DNA sites. We further demonstrate that the transcriptional properties of Msx and Dlx proteins display reciprocal inhibition. Specifically, Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities. Finally, we show that the expression patterns of representative Msx and Dlx genes (Msx1, Msx2, Dlx2, and Dlx5) overlap in mouse embryogenesis during limb bud and craniofacial development, consistent with the potential for their protein products to interact in vivo. Based on these observations, we propose that functional antagonism through heterodimer formation provides a mechanism for regulating the transcriptional actions of Msx and Dlx homeoproteins in vivo.

  9. The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

    PubMed

    Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

    2000-03-01

    Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

  10. Evidence that "brain-specific" FOX-1, FOX-2, and nPTB alternatively spliced isoforms are produced in the lens.

    PubMed

    Bitel, Claudine L; Nathan, Rachel; Wong, Patrick; Kuppasani, Sunil; Matsushita, Masafumi; Kanazawa, Hrioshi; Frederikse, Peter H

    2011-04-01

    Alternative RNA splicing is essential in development and more rapid physiological processes that include disease mechanisms. Studies over the last 20 years demonstrated that RNA binding protein families, which mediate the alternative splicing of a large percentage of genes in mammals, contain isoforms with mutually exclusive expression in non-neural and neural progenitor cells vs. post-mitotic neurons, and regulate the comprehensive reprogramming of alternative splicing during neurogenesis. Polypyrimidine tract binding (PTB) proteins and Fox-1 proteins also undergo mutually exclusive alternative splicing in neural and non-neural cells that regulates their tissue-specific expression and splicing activities. Over the past 50 years, striking morphological similarities noted between lens fiber cells and neurons suggested that cell biology processes and gene expression profiles may be shared as well. Here, we examined mouse and rat lenses to determine if alternative splicing of neuronal nPTB and Fox-1/Fox-2 isoforms also occurs in lenses. Immunoblot, immunofluorescence, and RT-PCR were used to examine expression and alternative splicing of transcripts in lens and brain. We demonstrated that exon 10 is predominantly included in nPTB transcripts consistent with nPTB protein in lenses, and that alternatively spliced Fox-1/-2 lens transcripts contain exons that have been considered neuron-specific. We identified a 3' alternative Fox-1 exon in lenses that encodes a nuclear localization signal consistent with its protein distribution detected in fiber cells. Neuronal alternative splicing of kinesin KIF1Bβ2 has been associated with PTB/nPTB and Fox-2, and we found that two 'neuron-specific' exons are also included in lenses. The present study provides evidence that alternative neuronal nPTB and Fox-1/Fox-2 isoforms are also produced in lenses. These findings raise questions regarding the extent these factors contribute to a similar reprogramming of alternative splicing during lens differentiation, and the degree that alternative gene transcripts produced during neurogenesis are also expressed in the lens.

  11. Systems Level Analysis of Histone H3 Post-translational Modifications (PTMs) Reveals Features of PTM Crosstalk in Chromatin Regulation*

    PubMed Central

    Schwämmle, Veit; Sidoli, Simone; Ruminowicz, Chrystian; Wu, Xudong; Lee, Chung-Fan; Helin, Kristian; Jensen, Ole N.

    2016-01-01

    Histones are abundant chromatin constituents carrying numerous post-translational modifications (PTMs). Such PTMs mediate a variety of biological functions, including recruitment of enzymatic readers, writers and erasers that modulate DNA replication, transcription and repair. Individual histone molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk. Using wild type and engineered mouse embryonic stem cells (mESCs) knocked out in components of the Polycomb Repressive Complex 2 (PRC2, Suz12−/−), PRC1 (Ring1A/B−/−) and (Dnmt1/3a/3b−/−) we performed comprehensive PTM analysis of histone H3 tails (50 aa) by utilizing quantitative middle-down proteome analysis by tandem mass spectrometry. We characterized combinatorial PTM features across the four mESC lines and then applied statistical data analysis to predict crosstalk between histone H3 PTMs. We detected an overrepresentation of positive crosstalk (codependent marks) between adjacent mono-methylated and acetylated marks, and negative crosstalk (mutually exclusive marks) among most of the seven characterized di- and tri-methylated lysine residues in the H3 tails. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites, including H3R2me, H3R8me and H3K37me. Integration of the H3 data with RNAseq data by coabundance clustering analysis of histone PTMs and histone modifying enzymes revealed correlations between PTM and enzyme levels. We conclude that middle-down proteomics is a powerful tool to determine conserved or dynamic interdependencies between histone marks, which paves the way for detailed investigations of the histone code. Histone H3 PTM data is publicly available in the CrossTalkDB repository at http://crosstalkdb.bmb.sdu.dk. PMID:27302890

  12. Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions

    PubMed Central

    Suehara, Yoshiyuki; Arcila, Maria; Wang, Lu; Hasanovic, Adnan; Ang, Daphne; Ito, Tatsuo; Kimura, Yuki; Drilon, Alexander; Guha, Udayan; Rusch, Valerie; Kris, Mark G.; Zakowski, Maureen F.; Rizvi, Naiyer; Khanin, Raya; Ladanyi, Marc

    2014-01-01

    Background The mutually exclusive pattern of the major driver oncogenes in lung cancer suggests that other mutually exclusive oncogenes exist. We performed a systematic search for tyrosine kinase (TK) fusions by screening all TKs for aberrantly high RNA expression levels of the 3′ kinase domain (KD) exons relative to more 5′ exons. Methods We studied 69 patients (including 5 never smokers and 64 current or former smokers) with lung adenocarcinoma negative for all major mutations in KRAS, EGFR, BRAF, MEK1, and HER2, and for ALK fusions (termed “pan-negative”). A NanoString-based assay was designed to query the transcripts of 90 TKs at two points: 5′ to the KD and within the KD or 3′ to it. Tumor RNAs were hybridized to the NanoString probes and analyzed for outlier 3′ to 5′ expression ratios. Presumed novel fusion events were studied by rapid amplification of cDNA ends (RACE) and confirmatory RT-PCR and FISH. Results We identified 1 case each of aberrant 3′ to 5′ ratios in ROS1 and RET. RACE isolated a GOPC-ROS1 (FIG-ROS1) fusion in the former and a KIF5B-RET fusion in the latter, both confirmed by RT-PCR. The RET rearrangement was also confirmed by FISH. The KIF5B-RET patient was one of only 5 never smokers in this cohort. Conclusion The KIF5B-RET fusion defines an additional subset of lung cancer with a potentially targetable driver oncogene enriched in never smokers with “pan-negative” lung adenocarcinomas. We also report for the first time in lung cancer the GOPC-ROS1 fusion previously characterized in glioma. PMID:23052255

  13. Cost-Utility Analysis of Cochlear Implantation in Australian Adults.

    PubMed

    Foteff, Chris; Kennedy, Steven; Milton, Abul Hasnat; Deger, Melike; Payk, Florian; Sanderson, Georgina

    2016-06-01

    Sequential and simultaneous bilateral cochlear implants are emerging as appropriate treatment options for Australian adults with sensory deficits in both cochleae. Current funding of Australian public hospitals does not provide for simultaneous bilateral cochlear implantation (CI) as a separate surgical procedure. Previous cost-effectiveness studies of sequential and simultaneous bilateral CI assumed 100% of unilaterally treated patients' transition to a sequential bilateral CI. This assumption does not place cochlear implantation in the context of the generally treated population. When mutually exclusive treatment options exist, such as unilateral CI, sequential bilateral CI, and simultaneous bilateral CI, the mean costs of the treated populations are weighted in the calculation of incremental cost-utility ratios. The objective was to evaluate the cost-utility of bilateral hearing aids (HAs) compared with unilateral, sequential, and simultaneous bilateral CI in Australian adults with bilateral severe to profound sensorineural hearing loss. Cost-utility analysis of secondary sources input to a Markov model. Australian health care perspective, lifetime horizon with costs and outcomes discounted 5% annually. Bilateral HAs as treatment for bilateral severe to profound sensorineural hearing loss compared with unilateral, sequential, and simultaneous bilateral CI. Incremental costs per quality adjusted life year (AUD/QALY). When compared with bilateral hearing aids the incremental cost-utility ratio for the CI treatment population was AUD11,160/QALY. The incremental cost-utility ratio was weighted according to the number of patients treated unilaterally, sequentially, and simultaneously, as these were mutually exclusive treatment options. No peer-reviewed articles have reported the incremental analysis of cochlear implantation in a continuum of care for surgically treated populations with bilateral severe to profound sensorineural hearing loss. Unilateral, sequential, and simultaneous bilateral CI were cost-effective when compared with bilateral hearing aids. Technologies that reduce the total number of visits for a patient could introduce additional cost efficiencies into clinical practice.

  14. Reduced Smad4 expression and DNA topoisomerase inhibitor chemosensitivity in non-small cell lung cancer.

    PubMed

    Ziemke, Michael; Patil, Tejas; Nolan, Kyle; Tippimanchai, Darinee; Malkoski, Stephen P

    2017-07-01

    Smad4 is a tumor suppressor that transduces transforming growth factor beta signaling and regulates genomic stability. We previously found that Smad4 knockdown in vitro inhibited DNA repair and increased sensitivity to DNA topoisomerase inhibitors. In this study, we assessed the association between reduced Smad4 expression and DNA topoisomerase inhibitor sensitivity in human non-small cell lung cancer (NSCLC) patients and evaluated the relationship between genomic alterations of Smad4 and molecular alterations in DNA repair molecules. We retrospectively identified NSCLC patients who received etoposide or gemcitabine. Chemotherapeutic response was quantified by RECIST 1.1 criteria and Smad4 expression was assessed by immunohistochemistry. Relationships between Smad4 mutation and DNA repair molecule mutations were evaluated using publically available datasets. We identified 28 individuals who received 30 treatments with gemcitabine or etoposide containing regimens for NSCLC. Reduced Smad4 expression was seen in 13/28 patients and was not associated with significant differences in clinical or pathologic parameters. Patients with reduced Smad4 expression had a larger response to DNA topoisomerase inhibitor containing regimens then patients with high Smad4 expression (-25.7% vs. -6.8% in lesion size, p=0.03); this relationship was more pronounced with gemcitabine containing regimens. The overall treatment response was higher in patients with reduced Smad4 expression (8/14 vs 2/16 p=0.02). Analysis of data from The Cancer Genome Atlas revealed that Smad4 mutation or homozygous loss was mutually exclusive with genomic alterations in DNA repair molecules. Reduced Smad4 expression may predict responsiveness to regimens that contain DNA topoisomerase inhibitors. That Smad4 signaling alterations are mutually exclusive with alterations in DNA repair machinery is consistent with an important role of Smad4 in regulating DNA repair. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Psychological and drug abuse symptoms associated with nonmedical use of opioid analgesics among adolescents.

    PubMed

    Boyd, Carol J; Young, Amy; McCabe, Sean E

    2014-01-01

    Approximately 18% of US adolescents engaged in prescription opioid abuse in 2013. However, this estimate may be misleading because it includes both medical misusers and nonmedical users, and there is evidence that these are 2 groups that differ relative to substance abuse and criminal risk. Thus, this study does not combine medical and nonmedical users; rather, it seeks to better understand the characteristics of nonmedical users. This was a school-based, cross-sectional study that was conducted during 2009-2010 in southeastern Michigan with a sample of 2627 adolescents using a Web-based survey. Three mutually exclusive groups were created based on responses regarding medical and nonmedical use of opioid analgesics. Group 1 had never used an opioid analgesic, Group 2 used an opioid analgesic only as prescribed, and Group 3 nonmedically used an opioid analgesic. In addition, Group 3 was divided into 2 mutually exclusive subgroups (self-treaters and sensation-seekers) based on reasons for nonmedical use. A series of multinomial logistic regressions were conducted to determine if the groups differed on the presence of pain, psychological symptoms (e.g., affective disorder, conduct disorder, attention-deficit/hyperactivity disorder [ADHD]), and drug abuse. Sixty-five percent (65.0%) of the sample was white/Caucasian and 29.5% was African American. The average age was 14.8 years (SD = 1.9). Seventy percent (70.4%; n = 1850) reported no lifetime opioid use, 24.5% (n = 644) were medical users, 3.5% (n = 92) were nonmedical users who used for pain relief only, and 1.6% (n = 41) were classified as nonmedical users for reasons other than for pain relief (e.g., to get high). Both medical users and nonmedical users reported more pain and substance abuse symptoms compared with never users. Those nonmedical users who used opioids for sensation-seeking motivations had greater odds of having psychological symptoms. These data support the need to further consider subgroups of nonmedical users of opioid analgesics.

  16. Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

    PubMed

    Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

    2017-12-08

    Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways. Published by Elsevier B.V.

  17. Wavelet analysis can sensitively describe dynamics of ethanol evoked local field potentials of the slug (Limax marginatus) brain.

    PubMed

    Schütt, Atsuko; Ito, Iori; Rosso, Osvaldo A; Figliola, Alejandra

    2003-10-30

    Odorants evoke characteristic, but complex, local field potentials (LFPs) in the molluscan brain. Wavelet tools in combination with Fourier analysis can detect and characterize hitherto unknown discrete, slow potentials underlying the conspicuous oscillations. Ethanol was one of the odorants that we have extensively studied (J. Neurosci. Methods, 119 (2002) 89). To detect new features and to elucidate their functions, we tested the wavelet tools on the ethanol-evoked LFP responses of the slug (Limax) procerebrum. Recordings were made in vitro from the neuropile and the cell layer. The present study led to the following findings: (i) Mutual exclusion. Energy concentrated mainly in two ranges, (a) 0.1-0.4 Hz and (b) 1.56-12.5 Hz, and the sum of energy remained constant throughout experiments regardless of the condition. A redistribution of relative energy within this sum seemed to occur in the course of main, possible interactions between the two components excluding each other ('mutual exclusion'). (ii) Transient signal ordering and disordering. Ethanol stimulation alternatingly evoked periods of strongly time evolving oscillation dominated by the energy of 1.56-12.5 Hz (increase of entropy=disordered or complexly ordered state) and those of near-silence were predominated by the energy of 0.1-0.4 Hz (decrease of entropy=ordered state). (iii) About 0.1 Hz slow wave oscillation. It was robust. The dominant energy oscillation and the resulting large entropy fluctuation were negatively correlated to each other, and revealed strong frequency-tuning or synchronization at this frequency. Our findings suggest that discrete slow waves play functionally important roles in the invertebrate brain, as widely known in vertebrate EEG. Wavelet tools allow an easy interpretation of several minutes of frequency variations in a single display and give precise information on stimulus-evoked complex change of the neural system describing the new state 'more ordered' or 'non-ordered or more complexly ordered'.

  18. Occurrence and characteristics of mutual interference between LIDAR scanners

    NASA Astrophysics Data System (ADS)

    Kim, Gunzung; Eom, Jeongsook; Park, Seonghyeon; Park, Yongwan

    2015-05-01

    The LIDAR scanner is at the heart of object detection of the self-driving car. Mutual interference between LIDAR scanners has not been regarded as a problem because the percentage of vehicles equipped with LIDAR scanners was very rare. With the growing number of autonomous vehicle equipped with LIDAR scanner operated close to each other at the same time, the LIDAR scanner may receive laser pulses from other LIDAR scanners. In this paper, three types of experiments and their results are shown, according to the arrangement of two LIDAR scanners. We will show the probability that any LIDAR scanner will interfere mutually by considering spatial and temporal overlaps. It will present some typical mutual interference scenario and report an analysis of the interference mechanism.

  19. Mutual enhancement of IL-2 and IL-7 on DNA vaccine immunogenicity mainly involves regulations on their receptor expression and receptor-expressing lymphocyte generation.

    PubMed

    Zhang, Yonghong; Liang, Shuang; Li, Xiujin; Wang, Liyue; Zhang, Jianlou; Xu, Jian; Huo, Shanshan; Cao, Xuebin; Zhong, Zhenyu; Zhong, Fei

    2015-07-09

    Our previous study showed that IL-2 and IL-7 could mutually enhance the immunogenicity of canine parvovirus VP2 DNA vaccine, although the underlying mechanism remained unknown. Here, we used the OVA gene as a DNA vaccine in a mouse model to test their enhancement on DNA vaccine immunogenicity and to explore the molecular mechanism. Results showed that both IL-2 and IL-7 genes significantly increased the immunogenicity of OVA DNA vaccine in mice. Co-administration of IL-2 and IL-7 genes with OVA DNA significantly increased OVA-specific antibody titers, T cell proliferation and IFN-γ production compared with IL-2 or IL-7 alone, confirming that IL-2 and IL-7 mutually enhanced DNA vaccine immunogenicity. Mechanistically, we have shown that IL-2 significantly stimulated generation of IL-7 receptor-expressing lymphocytes, and that IL-7 significantly induced IL-2 receptor expression. These results contribute to an explanation of the mechanism of the mutual effects of IL-2 and IL-7 on enhancing DNA vaccine immunogenicity and provided a basis for further investigation on their mutual effects on adjuvant activity and immune regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Self-concept in fairness and rule establishment during a competitive game: a computational approach

    PubMed Central

    Lee, Sang Ho; Kim, Sung-Phil; Cho, Yang Seok

    2015-01-01

    People consider fairness as well as their own interest when making decisions in economic games. The present study proposes a model that encompasses the self-concept determined by one's own kindness as a factor of fairness. To observe behavioral patterns that reflect self-concept and fairness, a chicken game experiment was conducted. Behavioral data demonstrates four distinct patterns; “switching,” “mutual rush,” “mutual avoidance,” and “unfair” patterns. Model estimation of chicken game data shows that a model with self-concept predicts those behaviors better than previous models of fairness, suggesting that self-concept indeed affects human behavior in competitive economic games. Moreover, a non-stationary parameter analysis revealed the process of reaching consensus between the players in a game. When the models were fitted to a continuous time window, the parameters of the players in a pair with “switching” and “mutual avoidance” patterns became similar as the game proceeded, suggesting that the players gradually formed a shared rule during the game. In contrast, the difference of parameters between the players in the “unfair” and “mutual rush” patterns did not become stable. The outcomes of the present study showed that people are likely to change their strategy until they reach a mutually beneficial status. PMID:26441707

  1. Cross Correlation versus Normalized Mutual Information on Image Registration

    NASA Technical Reports Server (NTRS)

    Tan, Bin; Tilton, James C.; Lin, Guoqing

    2016-01-01

    This is the first study to quantitatively assess and compare cross correlation and normalized mutual information methods used to register images in subpixel scale. The study shows that the normalized mutual information method is less sensitive to unaligned edges due to the spectral response differences than is cross correlation. This characteristic makes the normalized image resolution a better candidate for band to band registration. Improved band-to-band registration in the data from satellite-borne instruments will result in improved retrievals of key science measurements such as cloud properties, vegetation, snow and fire.

  2. The mutual inductance calculation between circular and quadrilateral coils at arbitrary attitudes using a rotation matrix for airborne transient electromagnetic systems

    NASA Astrophysics Data System (ADS)

    Ji, Yanju; Wang, Hongyuan; Lin, Jun; Guan, Shanshan; Feng, Xue; Li, Suyi

    2014-12-01

    Performance testing and calibration of airborne transient electromagnetic (ATEM) systems are conducted to obtain the electromagnetic response of ground loops. It is necessary to accurately calculate the mutual inductance between transmitting coils, receiving coils and ground loops to compute the electromagnetic responses. Therefore, based on Neumann's formula and the measured attitudes of the coils, this study deduces the formula for the mutual inductance calculation between circular and quadrilateral coils, circular and circular coils, and quadrilateral and quadrilateral coils using a rotation matrix, and then proposes a method to calculate the mutual inductance between two coils at arbitrary attitudes (roll, pitch, and yaw). Using coil attitude simulated data of an ATEM system, we calculate the mutual inductance of transmitting coils and ground loops at different attitudes, analyze the impact of coil attitudes on mutual inductance, and compare the computational accuracy and speed of the proposed method with those of other methods using the same data. The results show that the relative error of the calculation is smaller and that the speed-up is significant compared to other methods. Moreover, the proposed method is also applicable to the mutual inductance calculation of polygonal and circular coils at arbitrary attitudes and is highly expandable.

  3. As you reap, so shall you sow: coupling of harvesting and inoculating stabilizes the mutualism between termites and fungi

    PubMed Central

    Aanen, Duur K

    2006-01-01

    At present there is no consensus theory explaining the evolutionary stability of mutualistic interactions. However, the question is whether there are general ‘rules’, or whether each particular mutualism needs a unique explanation. Here, I address the ultimate evolutionary stability of the ‘agricultural’ mutualism between fungus-growing termites and Termitomyces fungi, and provide a proximate mechanism for how stability is achieved. The key to the proposed mechanism is the within-nest propagation mode of fungal symbionts by termites. The termites suppress horizontal fungal transmission by consuming modified unripe mushrooms (nodules) for food. However, these nodules provide asexual gut-resistant spores that form the inoculum of new substrate. This within-nest propagation has two important consequences: (i) the mutualistic fungi undergo severe, recurrent bottlenecks, so that the fungus is likely to be in monoculture and (ii) the termites ‘artificially’ select for high nodule production, because their fungal food source also provides the inoculum for the next harvest. I also provide a brief comparison of the termite–fungus mutualism with the analogous agricultural mutualism between attine ants and fungi. This comparison shows that—although common factors for the ultimate evolutionary stability of mutualisms can be identified—the proximate mechanisms can be fundamentally different between different mutualisms. PMID:17148364

  4. Use of sleeping trees by ursine colobus monkeys (Colobus vellerosus) demonstrates the importance of nearby food.

    PubMed

    Teichroeb, Julie A; Holmes, Teresa D; Sicotte, Pascale

    2012-07-01

    Examination of the characteristics and locations of sleeping sites helps to document the social and ecological pressures acting on animals. We investigated sleeping tree choice for four groups of Colobus vellerosus, an arboreal folivore, on 298 nights at the Boabeng-Fiema Monkey Sanctuary, Ghana using five non-mutually exclusive hypotheses: predation avoidance, access to food, range and resource defense, thermoregulation, and a null hypothesis of random selection. C. vellerosus utilized 31 tree species as sleeping sites and the species used differed per group depending on their availability. Groups used multiple sleeping sites and minimized their travel costs by selecting trees near feeding areas. The percentage that a food species was fed upon annually was correlated with the use of that species as a sleeping tree. Ninety percent of the sleeping trees were in a phenophase with colobus food items. Entire groups slept in non-food trees on only one night. These data strongly support the access to food hypothesis. Range and resource defense was also important to sleeping site choice. Groups slept in exclusively used areas of their home range more often than expected, but when other groups were spotted on the edge of the core area, focal groups approached the intruders, behaved aggressively, and slept close to them, seemingly to prevent an incursion into their core range. However, by sleeping high in the canopy, in large, emergent trees with dense foliage, positioning themselves away from the main trunk on medium-sized branches, and by showing low rates of site reuse, C. vellerosus also appeared to be avoiding predation in their sleeping site choices. Groups left their sleep sites later after cooler nights but did not show behavioral thermoregulation, such as huddling. This study suggests that access to food, range and resource defense, and predation avoidance were more important considerations in sleeping site selection than thermoregulation for ursine colobus.

  5. Cu(II) Binding to the Peptide Ala-His-His, a Chimera of the Canonical Cu(II)-Binding Motifs Xxx-His and Xxx-Zzz-His.

    PubMed

    Gonzalez, Paulina; Vileno, Bertrand; Bossak, Karolina; El Khoury, Youssef; Hellwig, Petra; Bal, Wojciech; Hureau, Christelle; Faller, Peter

    2017-12-18

    Peptides and proteins with the N-terminal motifs NH 2 -Xxx-His and NH 2 -Xxx-Zzz-His form well-established Cu(II) complexes. The canonical peptides are Gly-His-Lys and Asp-Ala-His-Lys (from the wound healing factor and human serum albumin, respectively). Cu(II) is bound to NH 2 -Xxx-His via three nitrogens from the peptide and an external ligand in the equatorial plane (called 3N form here). In contrast, Cu(II) is bound to NH 2 -Xxx-Zzz-His via four nitrogens from the peptide in the equatorial plane (called 4N form here). These two motifs are not mutually exclusive, as the peptides with the sequence NH 2 -Xxx-His-His contain both of them. However, this chimera has never been fully explored. In this work, we use a multispectroscopic approach to analyze the Cu(II) binding to the chimeric peptide Ala-His-His (AHH). AHH is capable of forming the 3N- and 4N-type complexes in a pH dependent manner. The 3N form predominates at pH ∼ 4-6.5 and the 4N form at ∼ pH 6.5-10. NMR experiments showed that at pH 8.5, where Cu(II) is almost exclusively bound in the 4N form, the Cu(II)-exchange between AHH or the amidated AHH-NH 2 is fast, in comparison to the nonchimeric 4N form (AAH). Together, the results show that the chimeric AHH can access both Cu(II) coordination types, that minor changes in the second (or further) coordination sphere can impact considerably the equilibrium between the forms, and that Cu kinetic exchange is fast even when Cu-AHH is mainly in the 4N form.

  6. Visual perception and social foraging in birds.

    PubMed

    Fernández-Juricic, Esteban; Erichsen, Jonathan T; Kacelnik, Alex

    2004-01-01

    Birds gather information about their environment mainly through vision by scanning their surroundings. Many prevalent models of social foraging assume that foraging and scanning are mutually exclusive. Although this assumption is valid for birds with narrow visual fields, these models have also been applied to species with wide fields. In fact, available models do not make precise predictions for birds with large visual fields, in which the head-up, head-down dichotomy is not accurate and, moreover, do not consider the effects of detection distance and limited attention. Studies of how different types of visual information are acquired as a function of body posture and of how information flows within flocks offer new insights into the costs and benefits of living in groups.

  7. Emergence of MPLW515 mutation in a patient with CALR deletion: Evidence of secondary acquisition of MPL mutation in the CALR clone.

    PubMed

    Partouche, Nicolas; Conejero, Carole; Barathon, Quentin; Moroch, Julien; Tulliez, Michel; Cordonnier, Catherine; Giraudier, Stephane

    2018-02-01

    Myeloproliferative neoplasms are characterized by transduction pathway recognized as mutually exclusive molecular abnormalities such as BCR-ABL translocation, JAK2V617F or JAK2 exon 12 mutations, MPL w515, and CALR mutations. However, in some rare cases, associations of such mutations are found in 1 patient. This can be related to 2 pathologies (at least 2 different clones harboring 2 mutations) or associated mutations in 1 clone. We describe here such an association of CALR and MPL mutations in a patient harboring the second mutation in a subclone during the phenotypic evolution of the myeloproliferative neoplasms. Copyright © 2017 John Wiley & Sons, Ltd.

  8. How to be a good professional: existentialist continuing professional development (CPD)

    PubMed Central

    Mulvey, Rachel

    2013-01-01

    This article reflects on the construct and practice of continuing professional development (CPD) and its significance for the professional careers workforce. The article presents the idea of the CPD triad and considers how professional bodies, employers and individuals can each benefit from a practitioner's ongoing commitment to continuing professional development. The tension between the practitioner's quest for lifelong learning is set against professional body demands, leading to the conclusion that these are not necessarily mutually exclusive. Consideration is given to propositional, practical and procedural knowledge, and to overall competence. The article explores an existentialist approach to professional learning, and concludes that, along with personal agency, this could usefully be adopted by career practitioners to weather turbulent times. PMID:24009404

  9. Employment Trajectories Beyond Retirement.

    PubMed

    Burkert, Carola; Hochfellner, Daniela

    2017-01-01

    Within the political and academic debate on working longer, post-retirement employment is discussed as an alternative to maintain older workers in the labor market. Our article enhances this discussion by studying determinants of transitions into post-retirement jobs within differing work environments of birth cohorts 1940-1942. We estimate proportional subhazard models accounting for competing risks using unique German social security data linked to pension accounts. Our findings suggest that individuals' preferences to take up post-retirement jobs are not mutually exclusive. Our study provides evidence that taking up post-retirement jobs is related to seeking financial security, continuity, and work ability, suggesting that public policy has to develop target-oriented support through a public policy mix of different measures aligned to the different peer groups in the labor market.

  10. Beauty and the brain: culture, history and individual differences in aesthetic appreciation.

    PubMed

    Jacobsen, Thomas

    2010-02-01

    Human aesthetic processing entails the sensation-based evaluation of an entity with respect to concepts like beauty, harmony or well-formedness. Aesthetic appreciation has many determinants ranging from evolutionary, anatomical or physiological constraints to influences of culture, history and individual differences. There are a vast number of dynamically configured neural networks underlying these multifaceted processes of aesthetic appreciation. In the current challenge of successfully bridging art and science, aesthetics and neuroanatomy, the neuro-cognitive psychology of aesthetics can approach this complex topic using a framework that postulates several perspectives, which are not mutually exclusive. In this empirical approach, objective physiological data from event-related brain potentials and functional magnetic resonance imaging are combined with subjective, individual self-reports.

  11. Study of techniques for redundancy verification without disrupting systems, phases 1-3

    NASA Technical Reports Server (NTRS)

    1970-01-01

    The problem of verifying the operational integrity of redundant equipment and the impact of a requirement for verification on such equipment are considered. Redundant circuits are examined and the characteristics which determine adaptability to verification are identified. Mutually exclusive and exhaustive categories for verification approaches are established. The range of applicability of these techniques is defined in terms of signal characteristics and redundancy features. Verification approaches are discussed and a methodology for the design of redundancy verification is developed. A case study is presented which involves the design of a verification system for a hypothetical communications system. Design criteria for redundant equipment are presented. Recommendations for the development of technological areas pertinent to the goal of increased verification capabilities are given.

  12. Beauty and the brain: culture, history and individual differences in aesthetic appreciation

    PubMed Central

    Jacobsen, Thomas

    2010-01-01

    Human aesthetic processing entails the sensation-based evaluation of an entity with respect to concepts like beauty, harmony or well-formedness. Aesthetic appreciation has many determinants ranging from evolutionary, anatomical or physiological constraints to influences of culture, history and individual differences. There are a vast number of dynamically configured neural networks underlying these multifaceted processes of aesthetic appreciation. In the current challenge of successfully bridging art and science, aesthetics and neuroanatomy, the neuro-cognitive psychology of aesthetics can approach this complex topic using a framework that postulates several perspectives, which are not mutually exclusive. In this empirical approach, objective physiological data from event-related brain potentials and functional magnetic resonance imaging are combined with subjective, individual self-reports. PMID:19929909

  13. Characterizing genomic alterations in cancer by complementary functional associations.

    PubMed

    Kim, Jong Wook; Botvinnik, Olga B; Abudayyeh, Omar; Birger, Chet; Rosenbluh, Joseph; Shrestha, Yashaswi; Abazeed, Mohamed E; Hammerman, Peter S; DiCara, Daniel; Konieczkowski, David J; Johannessen, Cory M; Liberzon, Arthur; Alizad-Rahvar, Amir Reza; Alexe, Gabriela; Aguirre, Andrew; Ghandi, Mahmoud; Greulich, Heidi; Vazquez, Francisca; Weir, Barbara A; Van Allen, Eliezer M; Tsherniak, Aviad; Shao, Diane D; Zack, Travis I; Noble, Michael; Getz, Gad; Beroukhim, Rameen; Garraway, Levi A; Ardakani, Masoud; Romualdi, Chiara; Sales, Gabriele; Barbie, David A; Boehm, Jesse S; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2016-05-01

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

  14. Disentangling the Correlated Evolution of Monogamy and Cooperation.

    PubMed

    Dillard, Jacqueline R; Westneat, David F

    2016-07-01

    Lifetime genetic monogamy, by increasing sibling relatedness, has been proposed as an important causal factor in the evolution of altruism. Monogamy, however, could influence the subsequent evolution of cooperation in other ways. We present several alternative, non-mutually exclusive, evolutionary processes that could explain the correlated evolution of monogamy and cooperation. Our analysis of these possibilities reveals that many ecological or social factors can affect all three variables of Hamilton's Rule simultaneously, thus calling for a more holistic, systems-level approach to studying the evolution of social traits. This perspective reveals novel dimensions to coevolutionary relationships and provides solutions for assigning causality in complex cases of correlated social trait evolution, such as the sequential evolution of monogamy and cooperation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Was Mackenbach right? Towards a practical political science of redistribution and health inequalities.

    PubMed

    Schrecker, Ted

    2017-07-01

    In 2010, Mackenbach reflected on England's lack of success in reducing health inequalities between 1997 and 2010, asserting that "it is difficult to imagine a longer window of opportunity for tackling health inequalities"; asking "[i]f this did not work, what will?"; and concluding that reducing health inequalities was not politically feasible at least in that jurisdiction. Exploring the empirics of that observation offers a window into the politics of reducing health inequalities. For purposes of future comparative research, I outline three (not mutually exclusive) perspectives on political feasibility, identify their implications for a political science of health inequalities, and explore what they mean for advocacy in support of reducing those inequalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

    PubMed

    Tang, Yew Chung; Ho, Szu-Chi; Tan, Elisabeth; Ng, Alvin Wei Tian; McPherson, John R; Goh, Germaine Yen Lin; Teh, Bin Tean; Bard, Frederic; Rozen, Steven G

    2018-03-22

    Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential drug targets in PTEN-deficient breast cancers. Therefore, with the aim of identifying potential targets for precision breast cancer therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of breast cancers. To discover broad-spectrum PTEN-SSL genes in breast cancer, we used a multi-step approach that started with (1) a genome-wide short interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast cancer cell lines; we then determined reproducibility of hits by (3) identification of overlaps between our results and reanalyzed data from 3 independent gene-essentiality screens, and finally, for selected candidate PTEN-SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity experiments in a panel of 19 cell lines or mutual exclusivity analysis of publicly available pan-cancer somatic mutation data. The screens (steps 1 and 2) and the reproducibility analysis (step 3) identified six candidate broad-spectrum PTEN-SSL genes (PIK3CB, ADAMTS20, AP1M2, HMMR, STK11, and NUAK1). PIK3CB was previously identified as PTEN-SSL, while the other five genes represent novel PTEN-SSL candidates. Confirmation studies (step 4) provided additional evidence that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01-015 selectively impaired viability in multiple PTEN-deficient breast cancer cell lines, while mutations affecting STK11 and PTEN were largely mutually exclusive across large pan-cancer data sets. Six genes showed PTEN-SSL patterns of activity in a large proportion of PTEN-deficient breast cancer cell lines and are potential specific vulnerabilities in PTEN-deficient breast cancer. Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference techniques can be recapitulated and exploited using the small molecule kinase inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for precision treatment of PTEN-deficient breast tumors.

  17. Mutual Information between Discrete Variables with Many Categories using Recursive Adaptive Partitioning

    PubMed Central

    Seok, Junhee; Seon Kang, Yeong

    2015-01-01

    Mutual information, a general measure of the relatedness between two random variables, has been actively used in the analysis of biomedical data. The mutual information between two discrete variables is conventionally calculated by their joint probabilities estimated from the frequency of observed samples in each combination of variable categories. However, this conventional approach is no longer efficient for discrete variables with many categories, which can be easily found in large-scale biomedical data such as diagnosis codes, drug compounds, and genotypes. Here, we propose a method to provide stable estimations for the mutual information between discrete variables with many categories. Simulation studies showed that the proposed method reduced the estimation errors by 45 folds and improved the correlation coefficients with true values by 99 folds, compared with the conventional calculation of mutual information. The proposed method was also demonstrated through a case study for diagnostic data in electronic health records. This method is expected to be useful in the analysis of various biomedical data with discrete variables. PMID:26046461

  18. Interacting epidemics on overlay networks

    NASA Astrophysics Data System (ADS)

    Funk, Sebastian; Jansen, Vincent A. A.

    2010-03-01

    The interaction between multiple pathogens spreading on networks connecting a given set of nodes presents an ongoing theoretical challenge. Here, we aim to understand such interactions by studying bond percolation of two different processes on overlay networks of arbitrary joint degree distribution. We find that an outbreak of a first pathogen providing immunity to another one spreading subsequently on a second network connecting the same set of nodes does so most effectively if the degrees on the two networks are positively correlated. In that case, the protection is stronger the more heterogeneous the degree distributions of the two networks are. If, on the other hand, the degrees are uncorrelated or negatively correlated, increasing heterogeneity reduces the potential of the first process to prevent the second one from reaching epidemic proportions. We generalize these results to cases where the edges of the two networks overlap to arbitrary amount, or where the immunity granted is only partial. If both processes grant immunity to each other, we find a wide range of possible situations of coexistence or mutual exclusion, depending on the joint degree distribution of the underlying networks and the amount of immunity granted mutually. These results generalize the concept of a coexistence threshold and illustrate the impact of large-scale network structure on the interaction between multiple spreading agents.

  19. [Identity and social integration: analysis of sociability in a mutual aid society (1902-1933)].

    PubMed

    León Sanz, Pilar

    2015-01-01

    This article studies the sociability evidenced in the fiestas and other celebrations held by the Breastfeeding Infant Clinic and periodically organized by La Conciliación Mutual Aid Society between 1902 and 1933 as recreational acts with educational purposes. La Conciliación (1902-1984) was founded in Pamplona as an exclusively male Catholic association (women were admitted from 1936) composed of workers, employers and protector members, with labor, healthcare, and economic objectives under a Mixed Board of Governors with representatives from the three cohorts. The description of the events and the analyses of the emotional practices are based on newspaper reports and the association's archives. The acts organized by the Breastfeeding Infant Clinic served to stimulate positive emotions and maternal feelings of piety and charity and to arouse a sense of social utility in the upper social classes. We acknowledge the regulatory component of the emotions that appeared in the fiesta of La Conciliatión: conferences and social events proposed a social model that reinforced the participation of members and their families in the association's ideological and religious goals. The performative character of emotions was designed to reinforce the identity of the members of La Conciliation and their social integration in the city. This model of sociability strengthened the project of La Conciliation.

  20. Conversion from mutual helicity to self-helicity observed with IRIS

    NASA Astrophysics Data System (ADS)

    Li, L. P.; Peter, H.; Chen, F.; Zhang, J.

    2014-10-01

    Context. In the upper atmosphere of the Sun observations show convincing evidence for crossing and twisted structures, which are interpreted as mutual helicity and self-helicity. Aims: We use observations with the new Interface Region Imaging Spectrograph (IRIS) to show the conversion of mutual helicity into self-helicity in coronal structures on the Sun. Methods: Using far UV spectra and slit-jaw images from IRIS and coronal images and magnetograms from SDO, we investigated the evolution of two crossing loops in an active region, in particular, the properties of the Si IV line profile in cool loops. Results: In the early stage two cool loops cross each other and accordingly have mutual helicity. The Doppler shifts in the loops indicate that they wind around each other. As a consequence, near the crossing point of the loops (interchange) reconnection sets in, which heats the plasma. This is consistent with the observed increase of the line width and of the appearance of the loops at higher temperatures. After this interaction, the two new loops run in parallel, and in one of them shows a clear spectral tilt of the Si IV line profile. This is indicative of a helical (twisting) motion, which is the same as to say that the loop has self-helicity. Conclusions: The high spatial and spectral resolution of IRIS allowed us to see the conversion of mutual helicity to self-helicity in the (interchange) reconnection of two loops. This is observational evidence for earlier theoretical speculations. Movie associated with Fig. 1 and Appendix A are available in electronic form at http://www.aanda.org

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