WorldWideScience

Sample records for repertoires vary depending

  1. Benzodiazepines consumption: does dependence vary with age?

    Science.gov (United States)

    Gérardin, Marie; Victorri-Vigneau, Caroline; Guerlais, Marylène; Guillou-Landreat, Morgane; Grall-Bronnec, Marie; Jolliet, Pascale

    2014-09-01

    We have compared two groups of chronic benzodiazepines (or zolpidem/zopiclone) users: "Seniors," aged 65 years or more, and "Adults," aged less than 65 years. The study took place in the Pays de Loire region. The questionnaire assesses dependence based on items from the DSM-IV. The analysis was based on 176 Senior questionnaires and 212 Adult questionnaires. Whereas Senior patients take benzodiazepines routinely with little negative consequences, Adults suffer from underlying psychological trouble, mention a higher consumption than planned, which causes negative consequences. 35.2% of Seniors are dependent on benzodiazepines versus 49.8% of Adults.

  2. Clonal progression during the T cell-dependent B cell antibody response depends on the immunoglobulin DH gene segment repertoire.

    Directory of Open Access Journals (Sweden)

    Ahmad eTrad

    2014-08-01

    Full Text Available The diversity of the third complementarity determining region of the Ig H chain is constrained by natural selection of immunoglobulin diversity (DH sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA. We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered D-DFS and D-iD strains were significantly reduced. An increased prevalence of IgM producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion as well as class switch recombination indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

  3. Flexible cultural repertoires

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz

    2016-01-01

    Despite extensive studies of street culture and the risks of offending and victimization in urban marginalized areas, little is known about the role of cultural repertoires for variation in victimization risks among young men not involved in crime. Based on two ethnographic studies, conducted...... varying cultural repertoires, in particularly heterogeneous flexible repertoires, influence offending and victimization patterns among young men in high-risk settings....... independently of the authors in neighbouring township areas of Cape Town, we offer insights into patterns of victimization among young men not involved in crime who live and attend school in the townships. Young men who perform decent cultural repertoires are highly exposed to victimization due to their moral...

  4. Condition dependence varies with mating success in male Drosophila bunnanda.

    Science.gov (United States)

    McGuigan, K

    2009-09-01

    Although key to sexual selection theories, condition dependence has proven a challenging area of empirical research. It is expected that availability of resources will affect both mean and variation of sexual trait expression, with lower mean and greater variation in harsher environments. Here, I manipulated the environment in a laboratory population of Drosophila bunnanda to test for condition dependence of sexually selected traits. Sexually successful and unsuccessful males differed in how the environment affected sexual trait expression. Specifically, sexual trait attractiveness declined more rapidly with declining resources in sexually unsuccessful males, consistent with the expectation that low quality males were less able to meet the greater signalling costs associated with harsher environments. This study illustrates the potential insights into condition dependence that might be gained through considering sexual trait expression and mating success within the same manipulative experimental design.

  5. The tubulin repertoire of Caenorhabditis elegans sensory neurons and its context‑dependent role in process outgrowth

    Science.gov (United States)

    Lockhead, Dean; Schwarz, Erich M.; O’Hagan, Robert; Bellotti, Sebastian; Krieg, Michael; Barr, Maureen M.; Dunn, Alexander R.; Sternberg, Paul W.; Goodman, Miriam B.

    2016-01-01

    Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division. They comprise αβ‑tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms, and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code. Here we use the well‑characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question through genetic dissection of process outgrowth both in vivo and in vitro. With single‑cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze process outgrowth and show that four tubulins (tba‑1, tba‑2, tbb‑1, and tbb‑2) function partially or fully redundantly, whereas two others (mec‑7 and mec‑12) perform specialized, context‑dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies among cell types and in vivo and in vitro contexts. PMID:27654945

  6. Antibody repertoire development in fetal and neonatal piglets. XX. B cell lymphogenesis is absent in the ileal Peyer's patches, their repertoire development is antigen dependent, and they are not required for B cell maintenance.

    Science.gov (United States)

    Butler, John E; Santiago-Mateo, Kristina; Sun, Xiu-Zhu; Wertz, Nancy; Sinkora, Marek; Francis, David H

    2011-11-15

    The continuous ileal Peyer's patches (IPP) of sheep are regarded as a type of mammalian bursal equivalent where B cells diversify their repertoire in an Ag-independent fashion. Anatomically and developmentally similar IPP occur in swine. Resection of ∼90% of the IPP in piglets at birth did not alter Ig levels in serum and secretions or retard diversification of the Ab repertoire when animals were maintained in isolators and colonized with a defined gut flora. Resection or sham surgery elevated IgG and IgA in serum and in lavage fluid from the gut, lung, and in saliva. No changes in the frequency of IgG-, IgA-, and IgM-containing cells in the spleen and peripheral lymph node were observed. Using an index that quantifies diversification of the VDJ repertoire, no differences were seen in three secondary lymphoid tissues between piglets lacking IPP and colonized controls, whereas both groups displayed >10-fold greater diversification than did late-term fetal piglets or piglets maintained germ-free. Somatic hypermutation was very low in fetal IPP and the IPP of germ-free piglets but increased 3- to 5-fold after colonization. D-J signal joint circles were not recovered in IPP, and V-DJ signal joint circles were 5-fold lower than in bone marrow and similar to those in thymus and spleen. We conclude that the porcine IPP are not a site of B cell lymphogenesis, do not undergo Ag-independent repertoire diversification, and are not primary lymphoid tissue since they are not required for maintenance of Ig levels in serum and secretions.

  7. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

    Science.gov (United States)

    Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

    2005-01-01

    The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

  8. Flexible cultural repertoires

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Zimmermann, Francisca

    2017-01-01

    rejection of crime-involved youth. Young men who perform flexible cultural repertoires, by incorporating and shifting between gang and decent repertoires, experience low victimization due to their adaptation to crime-involved youth. Findings emphasize the importance of detailed investigations of the way...

  9. Improved delay-dependent exponential stability for uncertain stochastic neural networks with time-varying delays

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, O.M., E-mail: madwind@chungbuk.ac.k [School of Electrical Engineering, Chungbuk National University, Cheongju (Korea, Republic of); Lee, S.M., E-mail: moony@daegu.ac.k [School of Electronics Engineering, Daegu University, Kyongsan (Korea, Republic of); Park, Ju H., E-mail: jessie@ynu.ac.k [Department of Electrical Engineering, Yeungnam University, Kyongsan (Korea, Republic of)

    2010-02-22

    This Letter investigates the problem of delay-dependent exponential stability analysis for uncertain stochastic neural networks with time-varying delay. Based on the Lyapunov stability theory, improved delay-dependent exponential stability criteria for the networks are established in terms of linear matrix inequalities (LMIs).

  10. Dose-dependent effect of N′-Nitrosodiethylamine on hepatic architecture, RBC rheology and polypeptide repertoire in Wistar rats

    Directory of Open Access Journals (Sweden)

    Mukherjee Devoshree

    2015-03-01

    Full Text Available N′-Nitrosodiethylamine (NDEA is an effective hepatotoxicant, carcinogen and mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1, is an extensively used experimental model. In the present study, we analysed the dose- and time-dependent effect of NDEA on hepatic damage, RBC rheology and proteomic profile in male Wistar rats. The rats, 5–6 weeks old, were divided into four groups: Group-1 served as control and received normal saline, Group-2 received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p. and the animals were sacrificed after one week; the rats of Group-3 received a single dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4 received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed. Various biochemical parameters such as ALT, AST, ALP and bilirubin were determined. Further, RBC rheology, histopathology (H&E staining of liver biopsies and polypeptide profiling (SDS-PAGE in sera and liver sections were also carried out both in control and NDEA treated groups. Our results showed a significant increase in all the biochemical parameters of the liver function test (p<0.05. In NDEA treated categories dacryocytes (tear drop cells, schistocytes (fragmented cells, codocytes (target cells, acanthocytes (spur cells and ovalocytes (oval cells were observed. H & E stained liver biopsies treated with NDEA showed abnormal liver architecture with severe haemorrhage, neutrophilic infiltration and dysplastic hepatocytes manifested in a dose-dependent manner. Software analysis of SDS-PAGE of control and NDEA treated rat sera and liver revealed qualitative and quantitative differences in polypeptide composition. Based on the presence/absence, polypeptides were classified in three different categories: (1 house-keeping, present in all the groups investigated; (2 novel, present in either control or NDEA treated group at any given time; (3 differential expression

  11. Delay dependent stability criteria for recurrent neural networks with time varying delays

    Institute of Scientific and Technical Information of China (English)

    Zhanshan WANG; Huaguang ZHANG

    2009-01-01

    This paper aims to present some delay-dependent global asymptotic stability criteria for recurrent neural networks with time varying delays.The obtained results have no restriction on the magnitude of derivative of time varying delay,and can be easily checked due to the form of linear matrix inequality.By comparison with some previous results,the obtained results are less conservative.A numerical example is utilized to demonstrate the effectiveness of the obtained results.

  12. Robust stability of time-varying uncertain systems with rational dependence on the uncertainty

    OpenAIRE

    2010-01-01

    Robust stability of time-varying uncertain systems is a key problem in automatic control. This note considers the case of linear systems with rational dependence on an uncertain time-varying vector constrained in a polytope, which is typically addressed in the literature by using the linear fractional representation (LFR). A novel sufficient condition for robust stability is derived in terms of a linear matrix inequality (LMI) feasibility test by exploiting homogeneous polynomial Lyapunov fun...

  13. Delay-dependent criteria for the robust stability of systems with time-varying delay

    Institute of Scientific and Technical Information of China (English)

    Min WU; Yong HE; Jinhua SHE

    2003-01-01

    The problem of delay-dependent robust stability for systems with titne-varying delay has been considered. By using the S-procedure and the Park' s inequality in the recent issue, a delay-dependent robust stability criterion which is less conservative than the previous results has been derived for time-delay systems with time-varying structured uncertainties. The same idea has also been easily extended to the systems with nonlinear perturbations. Numerical examples illustrated the effectiveness and the improvement of the proposed approach.

  14. Improving Delay-Range-Dependent Stability Condition for Systems with Interval Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Wei Qian

    2013-01-01

    Full Text Available This paper discusses the delay-range-dependent stability for systems with interval time-varying delay. Through defining the new Lyapunov-Krasovskii functional and estimating the derivative of the LKF by introducing new vectors, using free matrices and reciprocally convex approach, the new delay-range-dependent stability conditions are obtained. Two well-known examples are given to illustrate the less conservatism of the proposed theoretical results.

  15. Delay-Dependent Exponential Stability Criterion for BAM Neural Networks with Time-Varying Delays

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei Su; Yi-Ming Chen

    2008-01-01

    By employing the Lyapunov stability theory and linear matrix inequality (LMI) technique, delay dependent stability criterion is derived to ensure the exponential stability of bi-directional associative memory (BAM) neural networks with time-varying delays. The proposed condition can be checked easily by LMI control toolbox in Matlab. A numerical example is given to demonstrate the effectiveness of our results.

  16. Testing for time-varying long-range dependence in volatility for emerging markets

    Science.gov (United States)

    Cajueiro, Daniel O.; Tabak, Benjamin M.

    2005-02-01

    This paper tests whether volatility for equity returns for emerging markets possesses long-range dependence. Furthermore, the assertion of whether long-range dependence is time-varying is checked through a rolling sample approach. The empirical results suggest that there exists long-range dependence in emerging equity returns' volatility and also that it is time-varying. This assertion also holds true for Japan and the US, which are considered more developed markets. Moreover, these results are robust to “shuffling” the data to eliminate short-term autocorrelation. Therefore, they suggest that the class of GARCH processes, which are currently employed to analyze volatility of financial time series, is misspecified.

  17. Delay-Dependent Asymptotic Stability of Cohen-Grossberg Models with Multiple Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Xiaofeng Liao

    2007-01-01

    Full Text Available Dynamical behavior of a class of Cohen-Grossberg models with multiple time-varying delays is studied in detail. Sufficient delay-dependent criteria to ensure local and global asymptotic stabilities of the equilibrium of this network are derived by constructing suitable Lyapunov functionals. The obtained conditions are shown to be less conservative and restrictive than those reported in the known literature. Some numerical examples are included to demonstrate our results.

  18. T CELL REPERTOIRE COMPLEXITY IN SEVER COMBINED IMMUNODEFICIENCY PATIENTS AFTER BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    曹水; 李晓静

    2003-01-01

    Objective. To study thymus-dependent T cell development and T cell repertoire in human sever combined immunodeficiency (SCID) patients after HLA-identical or haploidentical T cell-depleted allogeneic bone marrow transplantation (BMT). Methods. Blood samples were obtained from 15 SCID patients before transplantation and at varying intervals thereafter. Quantitative competitive PCR assay and immunoscope analysis of the T cell receptor (TCR) Vβ repertoire were performed. Results. Before and within the first 100 days after transplantation, patients' peripheral blood mononuclear cell (PBMC) presented an oligoclonal or polyclonal skewed T cell repertoire, low T cell receptor excision circles (TRECs) values and predominance of CD45RO+ T cell. In contrast, the presence of high numbers of CD45RA+ T cells in bone marrow(BM) circulation reconstituted SCID patients (>100 days post-transplantation) correlated with active T cell production by the thymus as revealed by high TREC values, and a polyclonal T cell repertoire demonstrated by a Gaussian distribution of Vβ-specific peaks. Conclusions. Within one year after BMT, a normal T cell repertoire develops in SCID patients as a result of thymic output. The T cell receptor diversity is highly and positively correlated in these patients with TREC levels.

  19. Delay-range-dependent chaos synchronization approach under varying time-lags and delayed nonlinear coupling.

    Science.gov (United States)

    Zaheer, Muhammad Hamad; Rehan, Muhammad; Mustafa, Ghulam; Ashraf, Muhammad

    2014-11-01

    This paper proposes a novel state feedback delay-range-dependent control approach for chaos synchronization in coupled nonlinear time-delay systems. The coupling between two systems is esteemed to be nonlinear subject to time-lags. Time-varying nature of both the intrinsic and the coupling delays is incorporated to broad scope of the present study for a better-quality synchronization controller synthesis. Lyapunov-Krasovskii (LK) functional is employed to derive delay-range-dependent conditions that can be solved by means of the conventional linear matrix inequality (LMI)-tools. The resultant control approach for chaos synchronization of the master-slave time-delay systems considers non-zero lower bound of the intrinsic as well as the coupling time-delays. Further, the delay-dependent synchronization condition has been established as a special case of the proposed LK functional treatment. Furthermore, a delay-range-dependent condition, independent of the delay-rate, has been provided to address the situation when upper bound of the delay-derivative is unknown. A robust state feedback control methodology is formulated for synchronization of the time-delay chaotic networks against the L2 norm bounded perturbations by minimizing the L2 gain from the disturbance to the synchronization error. Numerical simulation results are provided for the time-delay chaotic networks to show effectiveness of the proposed delay-range-dependent chaos synchronization methodologies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  20. New delay-dependent stability criteria for neural networks with time-varying interval delay

    Energy Technology Data Exchange (ETDEWEB)

    Chen Jie, E-mail: chenjie@bit.edu.c [School of Automation, Beijing Institute of Technology, Beijing, 100081 (China); Sun Jian, E-mail: helios1225@yahoo.com.c [School of Automation, Beijing Institute of Technology, Beijing, 100081 (China); Liu, G.P., E-mail: gpliu@glam.ac.u [Faculty of Advanced Technology, University of Glamorgan, Pontypridd CF37 1DL (United Kingdom); CTGT Center in Harbin Institute of Technology, Harbin, 150001 (China); Rees, D., E-mail: drees@glam.ac.u [Faculty of Advanced Technology, University of Glamorgan, Pontypridd CF37 1DL (United Kingdom)

    2010-09-27

    The problem of stability analysis of neural networks with time-varying delay in a given range is investigated in this Letter. By introducing a new Lyapunov functional which uses the information on the lower bound of the delay sufficiently and an augmented Lyapunov functional which contains some triple-integral terms, some improved delay-dependent stability criteria are derived using the free-weighting matrices method. Numerical examples are presented to illustrate the less conservatism of the obtained results and the effectiveness of the proposed method.

  1. Delay-dependent stability analysis for discrete-time systems with time varying state delay

    Directory of Open Access Journals (Sweden)

    Stojanović Sreten B.

    2011-01-01

    Full Text Available The stability of discrete systems with time-varying delay is considered. Some sufficient delaydependent stability conditions are derived using an appropriate model transformation of the original system. The criteria are presented in the form of LMI, which are dependent on the minimum and maximum delay bounds. It is shown that the stability criteria are approximately the same conservative as the existing ones, but have much simpler mathematical form. The numerical example is presented to illustrate the applicability of the developed results.

  2. Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire

    Directory of Open Access Journals (Sweden)

    Cheng Cheng

    2011-02-01

    Full Text Available Abstract Background Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited. Results We analyzed 3 monoclonal TCR from TCR transgenic, Rag-/- mice using Illumina® sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters. Conclusions Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.

  3. Three African antelope species with varying water dependencies exhibit similar selective brain cooling.

    Science.gov (United States)

    Strauss, W Maartin; Hetem, Robyn S; Mitchell, Duncan; Maloney, Shane K; Meyer, Leith C R; Fuller, Andrea

    2016-05-01

    The use of selective brain cooling, where warm arterial blood destined for the brain is cooled in the carotid rete via counter-current heat exchange when in close proximity to cooler venous blood, contributes to the conservation of body water. We simultaneously measured carotid blood and hypothalamic temperature in four gemsbok, five red hartebeest and six blue wildebeest to assess the extent to which these free-living animals, with varying water dependency, routinely rely on selective brain cooling. We investigated the hypothesis that innate differences in selective brain cooling exist in large, sympatric artiodactyls with varying water dependency. All three species used selective brain cooling, without any discernible differences in three selective brain cooling indices. GLMMs revealed no species differences in the threshold temperature for selective brain cooling (z = 0.79, P = 0.43), the magnitude (z = -0.51, P = 0.61), or the frequency of selective brain cooling use (z = -0.47, P = 0.64), after controlling for carotid blood temperature and black globe temperature. Comparison of anatomical attributes of the carotid retes of the three species revealed that the volume (F 2,9 = 5.54, P = 0.03) and height (F 2,9 = 5.43, P = 0.03) of the carotid rete, per kilogram body mass, were greater in the red hartebeest than in the blue wildebeest. Nevertheless, intraspecific variability in the magnitude, the frequency of use, and the threshold temperature for selective brain cooling exceeded any interspecific variability in the three indices of selective brain cooling. We conclude that the three species have similar underlying ability to make use of selective brain cooling in an environment with freely available water. It remains to be seen to what extent these three species would rely on selective brain cooling, as a water conservation mechanism, when challenged by aridity, a condition likely to become prevalent throughout much of southern Africa under future climate change

  4. Nicotine-dependence-varying effects of smoking events on momentary mood changes among adolescents.

    Science.gov (United States)

    Selya, Arielle S; Updegrove, Nicole; Rose, Jennifer S; Dierker, Lisa; Tan, Xianming; Hedeker, Donald; Li, Runze; Mermelstein, Robin J

    2015-02-01

    Theories of nicotine addiction emphasize the initial role of positive reinforcement in the development of regular smoking behavior, and the role of negative reinforcement at later stages. These theories are tested here by examining the effects of amount smoked per smoking event on smoking-related mood changes, and how nicotine dependence (ND) moderates this effect. The current study examines these questions within a sample of light adolescent smokers drawn from the metropolitan Chicago area (N=151, 55.6% female, mean 17.7years). Ecological momentary assessment data were collected via handheld computers, and additional variables were drawn from a traditional questionnaire. Effects of the amount smoked per event on changes in positive affect (PA) and negative affect (NA) after vs. before smoking were examined, while controlling for subject-averaged amount smoked, age, gender, and day of week. ND-varying effects were examined using varying effect models to elucidate their change across levels of ND. The effect of the amount smoked per event was significantly associated with an increase in PA among adolescents with low-to-moderate levels of ND, and was not significant at high ND. Conversely, the effect of the amount smoked was significantly associated with a decrease in NA only for adolescents with low levels of ND. These findings support the role of positive reinforcement in early stages of dependent smoking, but do not support the role of negative reinforcement beyond early stages of smoking. Other potential contributing factors to the relationship between smoking behavior and PA/NA change are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. DNA priming prior to inactivated influenza A(H5N1) vaccination expands the antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults.

    Science.gov (United States)

    Khurana, Surender; Wu, Jian; Dimitrova, Milena; King, Lisa R; Manischewitz, Jody; Graham, Barney S; Ledgerwood, Julie E; Golding, Hana

    2013-08-01

    DNA priming improves the response to inactivated influenza A(H5N1) vaccination. We compared the immunogenicity of an H5 DNA prime (using strain A/Indonesia/5/2005) followed by an H5N1 monovalent inactivated vaccine boost at 4, 8, 12, 16, or 24 weeks to that of 2 doses of H5N1 monovalent inactivated vaccine in adults. Antibody epitope repertoires were elucidated by genome-fragment phage-display library analysis, and antibody avidities for HA1 and HA2 domains were measured by surface plasmon resonance. H5 DNA priming expanded the H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not the HA2) domain in an interval-dependent manner. Enhanced HA1 binding and avidity after an interval of ≥12 weeks between prime and boost correlated with improved neutralization of homologous and heterologous H5N1 strains. Clinical trials registration NCT01086657.

  6. Temperature and Magnetic Field Dependence of Critical Current Density of YBCO with Varying Flux Pinning Additions (POSTPRINT)

    Science.gov (United States)

    2010-03-01

    AFRL-RZ-WP-TP-2010-2083 TEMPERATURE AND MAGNETIC FIELD DEPENDENCE OF CRITICAL CURRENT DENSITY OF YBCO WITH VARYING FLUX PINNING ADDITIONS...MAGNETIC FIELD DEPENDENCE OF CRITICAL CURRENT DENSITY OF YBCO WITH VARYING FLUX PINNING ADDITIONS (POSTPRINT) 5a. CONTRACT NUMBER In-house 5b...20 ‒ 77 K. Films were prepared with pulsed laser deposition by (M/ YBCO )N multilayer or ( YBCO )1-x Mx single-target methods, for different M phases

  7. Delay-dependent robust H-infinity control for discrete-time uncertain systems with time-varying state delays

    Institute of Scientific and Technical Information of China (English)

    Xianming ZHANG; Min WU; Jinhua SHE; Dongsheng HAN

    2006-01-01

    This paper examines the delay-dependent H-infinity control problem for discrete-time linear systems with time-varying state delays and norm-bounded uncertainties. A new inequality for the finite sum of quadratic terms is first established. Then, some new delay-dependent criteria are derived by employing the new inequality to guarantee the robust stability of a closed-loop system with a prescribed H-infinity norm bound for all admissible uncertainties and bounded time-vary delays. A numerical example demonstrates that the proposed method is an improvement over existing ones.

  8. Delay-Dependent Exponential Stability for Discrete-Time BAM Neural Networks with Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Yonggang Chen

    2008-01-01

    Full Text Available This paper considers the delay-dependent exponential stability for discrete-time BAM neural networks with time-varying delays. By constructing the new Lyapunov functional, the improved delay-dependent exponential stability criterion is derived in terms of linear matrix inequality (LMI. Moreover, in order to reduce the conservativeness, some slack matrices are introduced in this paper. Two numerical examples are presented to show the effectiveness and less conservativeness of the proposed method.

  9. Local regularity for time-dependent tug-of-war games with varying probabilities

    Science.gov (United States)

    Parviainen, Mikko; Ruosteenoja, Eero

    2016-07-01

    We study local regularity properties of value functions of time-dependent tug-of-war games. For games with constant probabilities we get local Lipschitz continuity. For more general games with probabilities depending on space and time we obtain Hölder and Harnack estimates. The games have a connection to the normalized p (x , t)-parabolic equation ut = Δu + (p (x , t) - 2) Δ∞Nu.

  10. Early-Emerging Nicotine Dependence Has Lasting and Time-Varying Effects on Adolescent Smoking Behavior.

    Science.gov (United States)

    Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

    2016-08-01

    Novice and light adolescent smokers can develop symptoms of nicotine dependence, which predicts smoking behavior several years into the future. However, little is known about how the association between these early - emerging symptoms and later smoker behaviors may change across time from early adolescence into young adulthood. Data were drawn from a 7-year longitudinal study of experimental (dependence (assessed at age 15 ± 2 years) and future smoking frequency through age 24, after controlling for concurrent smoking heaviness. Baseline smoking status, race, and sex were examined as potential moderators of this relationship. Nicotine dependence symptoms assessed at approximately age 15 significantly predicted smoking frequency through age 24, over and above concurrent smoking heaviness, though it showed declining trends at older ages. Predictive validity was weaker among experimenters at young ages (dependence was a stronger predictor of smoking frequency for white smokers around baseline (ages 14.5-16), relative to nonwhite smokers. Nicotine dependence assessed in mid-adolescence predicts smoking frequency well into early adulthood, over and above concurrent smoking heaviness, especially among novice smokers and nonwhite smokers. Early-emerging nicotine dependence is a promising marker for screening and interventions aimed at preventing smoking progression.

  11. DELAY-DEPENDENT ROBUST STABILITY CRITERIA FOR UNCERTAIN SINGULAR NEUTRAL DIFFERENTIAL SYSTEMS WITH TIME-VARYING AND DISTRIBUTED DELAYS

    Institute of Scientific and Technical Information of China (English)

    Renji Han; Wei Jiang

    2009-01-01

    The problem of delay-dependent robust stability for uncertain linear singular neu-tral systems with time-varying and distributed delays is investigated. The uncertain-ties under consideration are norm bounded, and possibly time varying. Some new stability criteria, which are simpler and less conservative than existing results, are derived based on a new class of Lyapunov-Krasovskii functionals combined with the descriptor model transformation and the decomposition technique of coefficient matrix and formulated in the form of a linear matrix inequalitys (LMIs). Also, the criteria can be easily checked by the Matlab LMI toolbox.

  12. Delay-Dependent Robust Exponential Stability for Uncertain Neutral Stochastic Systems with Interval Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Weihua Mao

    2012-01-01

    Full Text Available This paper discusses the mean-square exponential stability of uncertain neutral linear stochastic systems with interval time-varying delays. A new augmented Lyapunov-Krasovskii functional (LKF has been constructed to derive improved delay-dependent robust mean-square exponential stability criteria, which are forms of linear matrix inequalities (LMIs. By free-weight matrices method, the usual restriction that the stability conditions only bear slow-varying derivative of the delay is removed. Finally, numerical examples are provided to illustrate the effectiveness of the proposed method.

  13. The tricks of the trait: neural implementation of personality varies with genotype-dependent serotonin levels.

    Science.gov (United States)

    Hahn, Tim; Heinzel, Sebastian; Notebaert, Karolien; Dresler, Thomas; Reif, Andreas; Lesch, Klaus-Peter; Jakob, Peter M; Windmann, Sabine; Fallgatter, Andreas J

    2013-11-01

    Gray's Reinforcement Sensitivity Theory (RST) has developed into one of the most prominent personality theories of the last decades. The RST postulates a Behavioral Inhibition System (BIS) modulating the reaction to stimuli indicating aversive events. A number of psychiatric disorders including depression, anxiety disorders, and psychosomatic illnesses have been associated with extreme BIS responsiveness. In recent years, neuroimaging studies have implicated the amygdala-septo-hippocampal circuit as an important neural substrate of the BIS. However, the neurogenetic basis of the regulation of this behaviorally and clinically essential system remains unclear. Investigating the effects of two functional genetic polymorphisms (tryptophan hydroxylase-2, G-703T, and serotonin transporter, serotonin transporter gene-linked polymorphic region) in 89 human participants, we find significantly different patterns of associations between BIS scores and amygdala-hippocampus connectivity during loss anticipation for genotype groups regarding both polymorphisms. Specifically, the correlation between amygdala-hippocampus connectivity and Gray's trait anxiety scores is positive in individuals homozygous for the TPH2 G-allele, while carriers of at least one T-allele show a negative association. Likewise, individuals homozygous for the 5-HTTLPR L(A) variant display a positive association while carriers of the S/L(G) allele show a trend towards a negative association. Thus, we show converging evidence of different neural implementation of the BIS depending on genotype-dependent levels of serotonin. We provide evidence suggesting that genotype-dependent serotonin levels and thus putative changes in the efficiency of serotonergic neurotransmission might not only alter brain activation levels directly, but also more fundamentally impact the neural implementation of personality traits. We outline the direct clinical implications arising from this finding and discuss the complex interplay

  14. Anatomical and Physiological Responses of Citrus Trees to Varying Boron Availability Are Dependent on Rootstock.

    Science.gov (United States)

    Mesquita, Geisa L; Zambrosi, Fernando C B; Tanaka, Francisco A O; Boaretto, Rodrigo M; Quaggio, José A; Ribeiro, Rafael V; Mattos, Dirceu

    2016-01-01

    In Citrus, water, nutrient transport and thereby fruit production, are influenced among other factors, by the interaction between rootstock and boron (B) nutrition. This study aimed to investigate how B affects the anatomical structure of roots and leaves as well as leaf gas exchange in sweet orange trees grafted on two contrasting rootstocks in response to B supply. Plants grafted on Swingle citrumelo or Sunki mandarin were grown in a nutrient solution of varying B concentration (deficient, adequate, and excessive). Those grafted on Swingle were more tolerant to both B deficiency and toxicity than those on Sunki, as revealed by higher shoot and root growth. In addition, plants grafted on Sunki exhibited more severe anatomical and physiological damages under B deficiency, showing thickening of xylem cell walls and impairments in whole-plant leaf-specific hydraulic conductance and leaf CO2 assimilation. Our data revealed that trees grafted on Swingle sustain better growth under low B availablitlity in the root medium and still respond positively to increased B levels by combining higher B absorption and root growth as well as better organization of xylem vessels. Taken together, those traits improved water and B transport to the plant canopy. Under B toxicity, Swingle rootstock would also favor plant growth by reducing anatomical and ultrastructural damage to leaf tissue and improving water transport compared with plants grafted on Sunki. From a practical point of view, our results highlight that B management in citrus orchards shall take into account rootstock varieties, of which the Swingle rootstock was characterized by its performance on regulating anatomical and ultrastructural damages, improving water transport and limiting negative impacts of B stress conditions on plant growth.

  15. Anatomical and Physiological Responses of Citrus Trees to Varying Boron Availability Is Dependent on Rootstock

    Directory of Open Access Journals (Sweden)

    Geisa Lima Mesquita

    2016-03-01

    Full Text Available In Citrus, water, nutrient transport and thereby fruit production, are influenced among other factors, by the interaction between rootstock and boron (B nutrition. This study aimed to investigate how B affects the anatomical structure of roots and leaves as well as leaf gas exchange in sweet orange trees grafted on two contrasting rootstocks in response to B supply. Plants grafted on Swingle citrumelo or Sunki mandarin were grown in a nutrient solution of varying B concentration (deficient, adequate, and excessive. Those grafted on Swingle were more tolerant to both B deficiency and toxicity than those on Sunki, as revealed by higher shoot and root growth. In addition, plants grafted on Sunki exhibited more severe anatomical and physiological damages under B deficiency, showing thickening of xylem cell walls and impairments in whole-plant, leaf-specific hydraulic conductance and leaf CO2 assimilation. Our data revealed that trees grafted on Swingle sustain better growth under low B availablitlity in the root medium and still respond positively to increased B levels by combining higher B absorption and root growth as well as better organization of xylem vessels. Taken together, those traits improved water and B transport to the plant canopy. Under B toxicity, Swingle rootstock would also favor plant growth by reducing anatomical and ultrastructural damage to leaf tissue and improving water transport compared with plants grafted on Sunki. From a practical point of view, our results highlight that B management in citrus orchards shall take into account rootstock varieties, of which the Swingle rootstock was characterized by its performance on regulating anatomical and ultrastructural damages, improving water transport and limiting negative impacts of B stress conditions on plant growth.

  16. EXPLAINING THE DISTINCTIVENESS OF MEXICAN-IMMIGRANT WELFARE BEHAVIORS: THE IMPORTANCE OF EMPLOYMENT-RELATED CULTURAL REPERTOIRES.

    Science.gov (United States)

    Van Hook, Jennifer; Bean, Frank D

    2009-06-01

    Social scientists generally seek to explain welfare-related behaviors in terms of economic choice, social structural, or culture of poverty theories. Because such explanations incompletely account for nativity differences in public assistance receipt among those of Mexican origin, this paper draws upon the sociology of migration and culture literatures to develop alternative materialist-based cultural repertoire hypotheses to explain the welfare behaviors of Mexican immigrants. We argue that immigrants from Mexico arrive and work in the United States under circumstances fostering employment-based cultural repertoires that, compared with natives and other immigrant groups, encourage less welfare participation (in part because such repertoires lead to faster welfare exits) and more post-welfare employment, especially in states with relatively more generous welfare-policies. Using individual-level data predating Welfare Reform from multiple panels of the Survey of Income and Program Participation (SIPP), merged with state-level information on welfare-benefit levels, we assess these ideas by examining immigrant-group differences in welfare receipt, retention, and transition to employment across locales with varying levels of welfare benefits. Overall, the results are consistent with the notion that cultural repertoires incline Mexican immigrants to utilize welfare not primarily to avoid work, cope with disadvantage, or perpetuate a culture of dependency, but rather mostly to minimize employment discontinuities. This result carries important theoretical and policy implications.

  17. Further improvement on delay-range-dependent stability results for linear systems with interval time-varying delays.

    Science.gov (United States)

    Liu, Pin-Lin

    2013-11-01

    This paper provides an improved delay-range-dependent stability criterion for linear systems with interval time-varying delays. No model transformation and no slack matrix variable are introduced. Furthermore, overly bounding for some cross term is avoided. The resulting criterion has advantages over some previous ones in that it involves fewer matrix variables but has less conservatism, which is established theoretically. Finally, two numerical examples are given to show the effectiveness of the proposed results.

  18. Delay-Dependent Stability Criteria of Uncertain Periodic Switched Recurrent Neural Networks with Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Xing Yin

    2011-01-01

    uncertain periodic switched recurrent neural networks with time-varying delays. When uncertain discrete-time recurrent neural network is a periodic system, it is expressed as switched neural network for the finite switching state. Based on the switched quadratic Lyapunov functional approach (SQLF and free-weighting matrix approach (FWM, some linear matrix inequality criteria are found to guarantee the delay-dependent asymptotical stability of these systems. Two examples illustrate the exactness of the proposed criteria.

  19. Evaluation of the repertoire of the TonB-dependent receptors of Haemophilus ducreyi for their role in virulence in humans.

    Science.gov (United States)

    Leduc, Isabelle; Banks, Keith E; Fortney, Kate R; Patterson, Kristine B; Billings, Steve D; Katz, Barry P; Spinola, Stanley M; Elkins, Christopher

    2008-04-15

    Haemophilus ducreyi contains 3 TonB-dependent receptors: the hemoglobin receptor HgbA, which is required for virulence in humans; the heme receptor TdhA; and an uncharacterized conserved hypothetical protein TdX (HD0646). A double tdX/tdhA mutant (FX527) was constructed on the background of a human-passaged variant of strain 35000 (35000HP). Six volunteers were infected with 35000HP at 3 sites on one arm and with FX527 at 3 sites on the other. The pustule formation rate was 55.6% (95% confidence interval [CI], 35.7%-75.4%) at 18 parent-strain sites and 44.4% (95% CI, 15.0%-73.9%) at 18 mutant-strain sites (P = .51). Similar amounts of 35000HP and FX527 were recovered from pustules in semiquantitative culture. Thus, TdX and TdhA are not necessary for virulence, whereas HgbA is both necessary and sufficient for virulence in humans. The data suggest that hemoglobin is the sole source of heme/iron used by H. ducreyi in vivo and has implications for the potential of HgbA as a vaccine.

  20. Controllable deterioration rate for time-dependent demand and time-varying holding cost

    Directory of Open Access Journals (Sweden)

    Mishra Vinod Kumar

    2014-01-01

    Full Text Available In this paper, we develop an inventory model for non-instantaneous deteriorating items under the consideration of the facts: deterioration rate can be controlled by using the preservation technology (PT during deteriorating period, and holding cost and demand rate both are linear function of time, which was treated as constant in most of the deteriorating inventory models. So in this paper, we developed a deterministic inventory model for non-instantaneous deteriorating items in which both demand rate and holding cost are a linear function of time, deterioration rate is constant, backlogging rate is variable and depend on the length of the next replenishment, shortages are allowed and partially backlogged. The model is solved analytically by minimizing the total cost of the inventory system. The model can be applied to optimizing the total inventory cost of non-instantaneous deteriorating items inventory for the business enterprises, where the preservation technology is used to control the deterioration rate, and demand & holding cost both are a linear function of time.

  1. Temperature Dependent Thermal Conductivity and Thermal Interface Resistance of Pentacene Thin Films with Varying Morphology.

    Science.gov (United States)

    Epstein, Jillian; Ong, Wee-Liat; Bettinger, Christopher J; Malen, Jonathan A

    2016-07-27

    Temperature dependent thermal conductivities and thermal interface resistances of pentacene (Pn) thin films deposited on silicon substrates and self-assembled monolayer-modified [octadecyltrichlorosilane (OTS) and (3-aminopropyl)triethoxysilane (APTES)] silicon substrates were measured using frequency domain thermoreflectance. Atomic force microscopy images were used to derive an effective film thickness for thermal transport that accounts for surface roughness. Data taken over a temperature range of 77-300 K for various morphologies and film thicknesses show that the thermal conductivity increases with increasing Pn grain size. The sum of the substrate-Pn and Pn-gold thermal interface resistances was isolated from the intrinsic thermal resistance of the Pn films and found to be independent of surface chemistry. Corresponding Kapitza lengths of approximately 150 nm are larger than the physical thicknesses of typical Pn thin films and indicate that the interfaces play a dominant role in the total thermal resistance. This study has implications for increasing the performance and effective thermal management of small molecule electronic and energy conversion devices.

  2. New Delay-Dependent Stability Criteria for Uncertain Neutral Systems with Mixed Time-Varying Delays and Nonlinear Perturbations

    Directory of Open Access Journals (Sweden)

    Hamid Reza Karimi

    2009-01-01

    Full Text Available The problem of stability analysis for a class of neutral systems with mixed time-varying neutral, discrete and distributed delays and nonlinear parameter perturbations is addressed. By introducing a novel Lyapunov-Krasovskii functional and combining the descriptor model transformation, the Leibniz-Newton formula, some free-weighting matrices, and a suitable change of variables, new sufficient conditions are established for the stability of the considered system, which are neutral-delay-dependent, discrete-delay-range-dependent, and distributed-delay-dependent. The conditions are presented in terms of linear matrix inequalities (LMIs and can be efficiently solved using convex programming techniques. Two numerical examples are given to illustrate the efficiency of the proposed method.

  3. Delay-dependent robust H-infinity filtering for uncertain linear systems with time-varying interval delay

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    This paper proposed a design method for delay-dependent robust H-infinity filter of linear systems with uncertainty and time-varying interval delay.The proposed method was shown to be much simpler than existing ones while giving significant improvement to the existing results.The key step in the method was to construct a special type of Lyapunov functional for the filter design problem.Unlike the existing techniques,the proposed method employed neither free weighting matrices nor any model transformation,le...

  4. Delay-dependent finite-time boundedness of a class of Markovian switching neural networks with time-varying delays.

    Science.gov (United States)

    Zhong, Qishui; Cheng, Jun; Zhao, Yuqing

    2015-07-01

    In this paper, a novel method is developed for delay-dependent finite-time boundedness of a class of Markovian switching neural networks with time-varying delays. New sufficient condition for stochastic boundness of Markovian jumping neural networks is presented and proved by an newly augmented stochastic Lyapunov-Krasovskii functional and novel activation function conditions, the state trajectory remains in a bounded region of the state space over a given finite-time interval. Finally, a numerical example is given to illustrate the efficiency and less conservative of the proposed method.

  5. Silent performances: Are "repertoires" really post-Kuhnian?

    Science.gov (United States)

    Sample, Matthew

    2017-02-01

    Ankeny and Leonelli (2016) propose "repertoires" as a new way to understand the stability of certain research programs as well as scientific change in general. By bringing a more complete range of social, material, and epistemic elements into one framework, they position their work as a correction to the Kuhnian impulse in philosophy of science and other areas of science studies. I argue that this "post-Kuhnian" move is not complete, and that repertoires maintain an internalist perspective. Comparison with an alternative framework, the "sociotechnical imaginaries" of Jasanoff and Kim (2015), illustrates precisely which elements of practice are externalized by Ankeny and Leonelli. Specifically, repertoires discount the role of audience, without whom the repertoires of science are unintelligible, and lack an explicit place for ethical and political imagination, which provide meaning for otherwise mechanical promotion of particular research programs. This comparison reveals, I suggest, two distinct modes of scholarship, one internalist and the other critical. While repertoires can be modified to meet the needs of critical STS scholars and to completely reject Kuhn's internalism, whether or not we do so depends on what we want our scholarship to achieve.

  6. The uncertain role of diversity dependence in species diversification and the need to incorporate time-varying carrying capacities.

    Science.gov (United States)

    Marshall, Charles R; Quental, Tiago B

    2016-04-01

    There is no agreement among palaeobiologists or biologists as to whether, or to what extent, there are limits on diversification and species numbers. Here, we posit that part of the disagreement stems from: (i) the lack of explicit criteria for defining the relevant species pools, which may be defined phylogenetically, ecologically or geographically; (ii) assumptions that must be made when extrapolating from population-level logistic growth to macro-evolutionary diversification; and (iii) too much emphasis being placed on fixed carrying capacities, rather than taking into account the opportunities for increased species richness on evolutionary timescales, for example, owing to increased biologically available energy, increased habitat complexity and the ability of many clades to better extract resources from the environment, or to broaden their resource base. Thus, we argue that a more effective way of assessing the evidence for and against the ideas of bound versus unbound diversification is through appropriate definition of the relevant species pools, and through explicit modelling of diversity-dependent diversification with time-varying carrying capacities. Here, we show that time-varying carrying capacities, either increases or decreases, can be accommodated through changing intrinsic diversification rates (diversity-independent effects), or changing the effects of crowding (diversity-dependent effects).

  7. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  8. Finite-time state-dependent Riccati equation for time-varying nonaffine systems: rigid and flexible joint manipulator control.

    Science.gov (United States)

    Korayem, M H; Nekoo, S R

    2015-01-01

    This article investigates finite-time optimal and suboptimal controls for time-varying systems with state and control nonlinearities. The state-dependent Riccati equation (SDRE) controller was the main framework. A finite-time constraint imposed on the equation changes it to a differential equation, known as the state-dependent differential Riccati equation (SDDRE) and this equation was applied to the problem reported in this study that provides general formulation and stability analysis. The following four solution methods were developed for solving the SDDRE; backward integration, state transition matrix (STM) and the Lyapunov based method. In the Lyapunov approach, both positive and negative definite solutions to related SDRE were used to provide suboptimal gain for the SDDRE. Finite-time suboptimal control is applied for robotic manipulator, as finite-time constraint strongly decreases state error and operation time. General state-dependent coefficient (SDC) parameterizations for rigid and flexible joint arms (prismatic or revolute joints) are introduced. By including nonlinear control inputs in the formulation, the actuator׳s limits can be inserted directly to the state-space equation of a manipulator. A finite-time SDRE was implemented on a 6R manipulator both in theory and experimentally. And a reduced 3R arm was modeled and tested as a flexible joint robot (FJR). Evaluations of load carrying capacity and operation time were investigated to assess the capability of this approach, both of which showed significant improvement.

  9. State-dependent differential Riccati equation to track control of time-varying systems with state and control nonlinearities.

    Science.gov (United States)

    Korayem, M H; Nekoo, S R

    2015-07-01

    This work studies an optimal control problem using the state-dependent Riccati equation (SDRE) in differential form to track for time-varying systems with state and control nonlinearities. The trajectory tracking structure provides two nonlinear differential equations: the state-dependent differential Riccati equation (SDDRE) and the feed-forward differential equation. The independence of the governing equations and stability of the controller are proven along the trajectory using the Lyapunov approach. Backward integration (BI) is capable of solving the equations as a numerical solution; however, the forward solution methods require the closed-form solution to fulfill the task. A closed-form solution is introduced for SDDRE, but the feed-forward differential equation has not yet been obtained. Different ways of solving the problem are expressed and analyzed. These include BI, closed-form solution with corrective assumption, approximate solution, and forward integration. Application of the tracking problem is investigated to control robotic manipulators possessing rigid or flexible joints. The intention is to release a general program for automatic implementation of an SDDRE controller for any manipulator that obeys the Denavit-Hartenberg (D-H) principle when only D-H parameters are received as input data.

  10. The density of knobs on Plasmodium falciparum-infected erythrocytes depends on developmental age and varies among isolates.

    Directory of Open Access Journals (Sweden)

    Katharina A Quadt

    Full Text Available BACKGROUND: The virulence of Plasmodium falciparum malaria is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs. The P. falciparum erythrocyte membrane protein 1 (PfEMP1 family expressed on dome-shaped protrusions called knobs on the IE surface is central to both. Differences in receptor specificity and affinity of expressed PfEMP1 are important for IE adhesiveness, but it is not known whether differences in the number and size of the knobs on which the PfEMP1 proteins are expressed also play a role. Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density. METHODOLOGY/PRINCIPAL FINDINGS: We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates from Ghanaian children with malaria and 10 P. falciparum isolates selected in vitro for expression of a particular PfEMP1 protein (VAR2CSA were examined. Knob density increased from ∼20 h to ∼35 h post-invasion, with significant variation among isolates. The knob density ex vivo, which was about five-fold higher than following long-term in vitro culture, started to decline within a few months of culture. Although knob diameter and height varied among isolates, we did not observe significant time-dependent variation in these dimensions. CONCLUSIONS/SIGNIFICANCE: The density of knobs on the P. falciparum-IE surface depends on time since invasion, but is also determined by the infecting isolate in a time-independent manner. This is the first study to quantitatively evaluate knob densities and dimensions on different P. falciparum isolates, to examine ex vivo isolates from humans, and to compare ex vivo and long-term in vitro-cultured isolates. Our findings contribute to the understanding of the interaction between P. falciparum parasites and the

  11. Praxis and Poiesis in Piano Repertoire Preparation

    Science.gov (United States)

    Dos Santos, Regina Antunes Teixeira; Hentschke, Liane

    2011-01-01

    The piano repertoire preparation of three undergraduate students at three different academic levels--the first, fifth and eighth semesters--was followed during an academic semester. A phenomenological approach was used to collect data in three stages: an introductory interview, observations of the repertoire under preparation and a final…

  12. Praxis and Poiesis in Piano Repertoire Preparation

    Science.gov (United States)

    Dos Santos, Regina Antunes Teixeira; Hentschke, Liane

    2011-01-01

    The piano repertoire preparation of three undergraduate students at three different academic levels--the first, fifth and eighth semesters--was followed during an academic semester. A phenomenological approach was used to collect data in three stages: an introductory interview, observations of the repertoire under preparation and a final…

  13. THE LYMPH SELF ANTIGEN REPERTOIRE

    Directory of Open Access Journals (Sweden)

    Laura eSantambrogio

    2013-12-01

    Full Text Available The lymphatic fluid originates from the interstitial fluid which bathes every parenchymal organ and reflects the omic composition of the tissue from which it originates in its physiological or pathological signature. Several recent proteomic analyses have mapped the proteome-degradome and peptidome of this immunologically relevant fluid pointing to the lymph as an important source of tissue-derived self-antigens. A vast array of lymph-circulating peptides have been mapped deriving from a variety of processing pathways including caspases, cathepsins, MMPs, ADAMs, kallikreins, calpains and granzymes, among others. These self peptides can be directly loaded on circulatory dendritic cells and expand the self-antigenic repertoire available for central and peripheral tolerance.

  14. The myelin basic protein-specific T cell repertoire in (transgenic) Lewis rat/SCID mouse chimeras: preferential V beta 8.2 T cell receptor usage depends on an intact Lewis thymic microenvironment.

    Science.gov (United States)

    Kääb, G; Brandl, G; Marx, A; Wekerle, H; Bradl, M

    1996-05-01

    In the Lewis rat, myelin basic protein (MBP)-specific, encephalitogenic T cells preferentially recognize sequence 68-88, and use the V beta 8.2 gene to encode their T cell receptors. To analyze the structural prerequisites for the development of the MBP-specific T cell repertoire, we reconstituted severe-combined immunodeficient (SCID) mice with fetal (embryonic day 15-16) Lewis rat lymphoid tissue, and then isolated MBP-specific T cell lines from the adult chimeras after immunization. Two types of chimera were constructed: SCID mice reconstituted with rat fetal liver cells only, allowing T cell maturation within a chimeric SCID thymus consisting of mouse thymic epithelium and rat interdigitating dendritic cells, and SCID mice reconstituted with rat fetal liver cells and rat fetal thymus grafts, allowing T cell maturation within the chimeric SCID and the intact Lewis rat thymic microenvironment. Without exception, the T cell lines isolated from MBP-immunized SCID chimeras were restricted by MHC class II of the Lewis rat (RT1.B1), and none by I-Ad of the SCID mouse. Most of the T cell lines recognized the immunodominant MBP epitope 68-88. In striking contrast to intact Lewis rats, in SCID mice reconstituted by rat fetal liver only, MBP-specific T cell clones used a seemingly random repertoire of V beta genes without a bias for V beta 8.2. In chimeras containing fetal Lewis liver plus fetal thymus grafted under the kidney capsule, however, dominant utilization of V beta 8.2 was restored. The migration of liver-derived stem cells through rat thymus grafts was documented by combining fetal tissues from wild-type and transgenic Lewis rats. The results confirm that the recognition of the immunodominant epitope 68-88 by MBP-specific encephalitogenic T cells is a genetically determined feature of the Lewis rat T cell repertoire. They further suggest that the formation of the repertoire requires T cell differentiation in a syngeneic thymic microenvironment.

  15. BRAZILIAN FEMINIST MOVEMENT: REPERTOIRE AND STRATEGIES FOR ACTION

    Directory of Open Access Journals (Sweden)

    Carla de Paiva Bezerra

    2014-08-01

    Full Text Available This article aims at analyzing the development of and changes in, the repertoire and strategies for action of the Brazilian feminist movement, in the period between the democratic “re-opening” set in the 1980s and the first decade of the XXI century. Our interest is centered in two foci of analysis: on the one hand, it focuses on the movement’s positioning in relation to the State, which varied from a situation of opposition, or even of indifference, to direct attempts at influencing public policies and actions in the State sphere, whether through party politics or participative institutions. On the other hand, we are interested in analyzing how, and in which specific moments, agency beyond the national feminist frontiers takes place and in which measure this influences the local repertoires and vice-versa.

  16. New delay-dependent criterion for the stability of recurrent neural networks with time-varying delay

    Institute of Scientific and Technical Information of China (English)

    ZHANG HuaGuang; WANG ZhanShan

    2009-01-01

    This paper is concerned with the global asymptotic stability of a class of recurrent neural networks with interval time-varying delay. By constructing a suitable Lyapunov functional, a new criterion is established to ensure the global asymptotic stability of the concerned neural networks, which can be expressed in the form of linear matrix inequality and independent of the size of derivative of time varying delay. Two numerical examples show the effectiveness of the obtained results.

  17. Differences in Early Maladaptive Schemas in a Sample of Alcohol and Opioid Dependent Women: Do Schemas Vary Across Disorders?

    Science.gov (United States)

    Shorey, Ryan C.; Stuart, Gregory L.; Anderson, Scott

    2012-01-01

    Research suggests that there may be differences between individuals diagnosed with alcohol dependence and individuals diagnosed with opioid dependence on co-morbid mental health problems (e.g., personality disorders, mood disorders, etc.). The current study examined whether there were differences in early maladaptive schemas, which are theorized to underlie mental health problems, among women diagnosed with alcohol dependence or opioid dependence who were seeking treatment for their substance use (N = 420). Results showed that opioid dependent women scored higher on 2 of the 18 early maladaptive schemas, particularly the schemas of dependence and punitiveness. Overall, these findings suggest that early maladaptive schemas may be largely consistent across women diagnosed with alcohol or opioid dependence. Implications of these findings for future research and treatment are discussed. PMID:23494129

  18. Human gut microbiota: repertoire and variations

    Directory of Open Access Journals (Sweden)

    Jean-Christophe eLagier

    2012-11-01

    Full Text Available The composition of human gut microbiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gut microbiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism.

  19. New Delay-Dependent Stability of Uncertain Discrete-Time Switched Systems with Time-Varying Delays

    Institute of Scientific and Technical Information of China (English)

    Liang Lin XIONG; Shou Ming ZHONG; Mao YE

    2011-01-01

    This paper deals with the issues of robust stability for uncertain discrete-time switched systems with mode-dependent time delays. Based on a novel difference inequality and a switched Lyapunov function, new delay-dependent stability criteria are formulated in terms of linear matrix inequalities (LMIs) which are not contained in known literature. A numerical example is given to demonstrate that the proposed criteria improves some existing results significantly with much less computational effort.

  20. Novel delay-dependent stability analysis of Takagi-Sugeno fuzzy uncertain neural networks with time varying delays

    Institute of Scientific and Technical Information of China (English)

    M.Syed Ali

    2012-01-01

    This paper presents the stability analysis for a class of neural networks with time varying delays that are represented by the Takagi-Sugeno (T-S) model.The main results given here focus on the stability criteria using a new Lyapunov functional.New relaxed conditions and new linear matrix inequality-based designs are proposed that outperform the previous results found in the literature.Numerical examples are provided to show that the achieved conditions are less conservative than the existing ones in the literature.

  1. New Delay-Dependent Robust Exponential Stability Criteria of LPD Neutral Systems with Mixed Time-Varying Delays and Nonlinear Perturbations

    Directory of Open Access Journals (Sweden)

    Sirada Pinjai

    2013-01-01

    Full Text Available This paper is concerned with the problem of robust exponential stability for linear parameter-dependent (LPD neutral systems with mixed time-varying delays and nonlinear perturbations. Based on a new parameter-dependent Lyapunov-Krasovskii functional, Leibniz-Newton formula, decomposition technique of coefficient matrix, free-weighting matrices, Cauchy’s inequality, modified version of Jensen’s inequality, model transformation, and linear matrix inequality technique, new delay-dependent robust exponential stability criteria are established in terms of linear matrix inequalities (LMIs. Numerical examples are given to show the effectiveness and less conservativeness of the proposed methods.

  2. The density of knobs on Plasmodium falciparum-infected erythrocytes depends on developmental age and varies among isolates

    DEFF Research Database (Denmark)

    Quadt, Katharina A; Barfod, Lea; Andersen, Daniel;

    2012-01-01

    BACKGROUND: The virulence of Plasmodium falciparum malaria is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on dome....... Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density. METHODOLOGY/PRINCIPAL FINDINGS: We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates...

  3. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.

    Science.gov (United States)

    De Foubert, G; Carney, S L; Robinson, C S; Destexhe, E J; Tomlinson, R; Hicks, C A; Murray, T K; Gaillard, J P; Deville, C; Xhenseval, V; Thomas, C E; O'Neill, M J; Zetterström, T S C

    2004-01-01

    Recent studies indicate that brain-derived neurotrophic factor (BDNF) may be implicated in the clinical action of antidepressant drugs. Repeated (2-3 weeks) administration of antidepressant drugs increases BDNF gene expression. The onset of this response as well as concomitant effects on the corresponding BDNF protein is however, unclear. The present study investigated the effects of acute and chronic administration of the selective serotonin reuptake inhibitor, fluoxetine (10mg/kg p.o.), upon regional rat brain levels of BDNF mRNA and protein expression. To improve the clinical significance of the study, fluoxetine was administered orally and mRNA and protein levels were determined ex vivo using the techniques of in situ hybridisation histochemistry and immunocytochemistry respectively. Direct measurement of BDNF protein was also carried out using enzyme-linked immunosorbent assay (ELISA). Four days of once daily oral administration of fluoxetine induced decreases in BDNF mRNA (hippocampus, medial habenular and paraventricular thalamic nuclei). Whilst 7 days of treatment showed a non-significant increase in BDNF mRNA, there were marked and region-specific increases following 14 days of treatment. BDNF protein levels remained unaltered until 21 days of fluoxetine treatment, when the numbers of BDNF immunoreactive cells were increased, reaching significance in the pyramidal cell layer of CA1 and CA3 regions of Ammon's horn (CA1 and CA3) but not in the other sub-regions of the hippocampus. Indicative of the highly regional change within the hippocampus, the ELISA method failed to demonstrate significant up-regulation at 21 days, measuring levels of BDNF protein in the whole hippocampus. In contrast to the detected time dependent and biphasic response of the BDNF gene, activity-regulated, cytoskeletal-associated protein (Arc) mRNA showed a gradual increase during the 14-day course of treatment. The results presented here show that BDNF is expressed differentially

  4. Spotlight on the Underdogs—An Analysis of Underrepresented Alternaria Mycotoxins Formed Depending on Varying Substrate, Time and Temperature Conditions

    Directory of Open Access Journals (Sweden)

    Theresa Zwickel

    2016-11-01

    Full Text Available Alternaria (A. is a genus of widespread fungi capable of producing numerous, possibly health-endangering Alternaria toxins (ATs, which are usually not the focus of attention. The formation of ATs depends on the species and complex interactions of various environmental factors and is not fully understood. In this study the influence of temperature (7 °C, 25 °C, substrate (rice, wheat kernels and incubation time (4, 7, and 14 days on the production of thirteen ATs and three sulfoconjugated ATs by three different Alternaria isolates from the species groups A. tenuissima and A. infectoria was determined. High-performance liquid chromatography coupled with tandem mass spectrometry was used for quantification. Under nearly all conditions, tenuazonic acid was the most extensively produced toxin. At 25 °C and with increasing incubation time all toxins were formed in high amounts by the two A. tenuissima strains on both substrates with comparable mycotoxin profiles. However, for some of the toxins, stagnation or a decrease in production was observed from day 7 to 14. As opposed to the A. tenuissima strains, the A. infectoria strain only produced low amounts of ATs, but high concentrations of stemphyltoxin III. The results provide an essential insight into the quantitative in vitro AT formation under different environmental conditions, potentially transferable to different field and storage conditions.

  5. Polar polycyclic aromatic compounds from different coal types show varying mutagenic potential, EROD induction and bioavailability depending on coal rank.

    Science.gov (United States)

    Meyer, Wiebke; Seiler, Thomas-Benjamin; Schwarzbauer, Jan; Püttmann, Wilhelm; Hollert, Henner; Achten, Christine

    2014-10-01

    Investigations of the bioavailability and toxicity of polycyclic aromatic compounds (PAC) have rarely considered the heterogeneity of coals and the impact of more polar PAC besides polycyclic aromatic hydrocarbons (PAH). Earlier, we investigated the toxicity of eight heterogeneous coals and their extracts. In the present study, the hazard potential with respect to mechanism-specific toxicity of polar fractions of dichloromethane extracts from coals was studied. Polar extract fractions of all coal types except for anthracite induced EROD activity (determined in RTL-W1 cells), independent of coal type (Bio-TEQs between 23 ± 16 and 52 ± 22 ng/g). The polar fractions of all bituminous coal extracts revealed mutagenic activity (determined using the Ames Fluctuation test). No significant mutation induction was detected for the polar extract fractions from the lignite, sub-bituminous coal and anthracite samples, which indicates a higher dependency on coal type for polar PAC here. Additionally, information on bioavailability was derived from a bioaccumulation test using the deposit-feeding oligochaete Lumbriculus variegatus which was exposed for 28 days to ground coal samples. Despite the high toxic potential of most coal extracts and a reduced biomass of Lumbriculus in bituminous coal samples, bioaccumulation of PAH and mortality after 28 days were found to be low. Limited bioaccumulation of PAH (up to 3.6 ± 3.8 mg/kg EPA-PAH) and polar PAC were observed for all coal samples. A significant reduction of Lumbriculus biomass was observed in the treatments containing bituminous coals (from 0.019 ± 0.004 g to 0.046 ± 0.011 g compared to 0.080 ± 0.025 g per replicate in control treatments). We conclude that bioavailability of native PAC from coals including polar PAC is low for all investigated coal types. In comparison to lignite, sub-bituminous coals and anthracite, the bioavailability of PAC from bituminous coals is slightly increased.

  6. T cell repertoires and competitive exclusion

    NARCIS (Netherlands)

    Boer, R.J. de; Perelson, A.S.

    1994-01-01

    Self-renewal is generally thought to play a major role in the maintenance of the T-cell repertoire. Here we develop a set of mathematical models for T-cell activation by peptides on antigen presenting cells (APCs). We show that competition between T cells is inherent to the processes involved in T c

  7. The Repertoire of Black Popular Culture

    National Research Council Canada - National Science Library

    Nelson, Angela

    2009-01-01

    ... in the diaspora), of the black aesthetic (the distinctive cultural repertoires out of which popular representations were made), and of the black counternarratives we have struggled to voice" (28). Hall further declares that "good" black popular culture can pass the test of authenticity when the form or product refers to the black experience (his...

  8. Englishized Style Repertoire in Modern Japanese Literature.

    Science.gov (United States)

    Ono, Reiko

    1992-01-01

    The roles played by English borrowings in modern Japanese literary works are examined. After a brief summary of previous studies, this paper describes the style repertoire and the kinds of stylistic effects produced in Japanese literature by English borrowings, such as attention attractors and in-group-identity markers. (23 references) (Author/LB)

  9. Methanol emissions from maize: Ontogenetic dependence to varying light conditions and guttation as an additional factor constraining the flux

    Science.gov (United States)

    Mozaffar, A.; Schoon, N.; Digrado, A.; Bachy, A.; Delaplace, P.; du Jardin, P.; Fauconnier, M.-L.; Aubinet, M.; Heinesch, B.; Amelynck, C.

    2017-03-01

    Because of its high abundance and long lifetime compared to other volatile organic compounds in the atmosphere, methanol (CH3OH) plays an important role in atmospheric chemistry. Even though agricultural crops are believed to be a large source of methanol, emission inventories from those crop ecosystems are still scarce and little information is available concerning the driving mechanisms for methanol production and emission at different developmental stages of the plants/leaves. This study focuses on methanol emissions from Zea mays L. (maize), which is vastly cultivated throughout the world. Flux measurements have been performed on young plants, almost fully grown leaves and fully grown leaves, enclosed in dynamic flow-through enclosures in a temperature and light-controlled environmental chamber. Strong differences in the response of methanol emissions to variations in PPFD (Photosynthetic Photon Flux Density) were noticed between the young plants, almost fully grown and fully grown leaves. Moreover, young maize plants showed strong emission peaks following light/dark transitions, for which guttation can be put forward as a hypothetical pathway. Young plants' average daily methanol fluxes exceeded by a factor of 17 those of almost fully grown and fully grown leaves when expressed per leaf area. Absolute flux values were found to be smaller than those reported in the literature, but in fair agreement with recent ecosystem scale flux measurements above a maize field of the same variety as used in this study. The flux measurements in the current study were used to evaluate the dynamic biogenic volatile organic compound (BVOC) emission model of Niinemets and Reichstein. The modelled and measured fluxes from almost fully grown leaves were found to agree best when a temperature and light dependent methanol production function was applied. However, this production function turned out not to be suitable for modelling the observed emissions from the young plants

  10. Temporal stability and change in the social call repertoire of migrating humpback whales.

    Science.gov (United States)

    Rekdahl, Melinda L; Dunlop, Rebecca A; Noad, Michael J; Goldizen, Anne W

    2013-03-01

    Quantifying the stability of a species vocal repertoire is fundamental for further investigations into repertoire function and geographic variation. Changes to the repertoire of sounds used in the song displays of male humpback whales have been well studied. In contrast, little is known about the stability of this species' non-song vocal calls. The stability of the social call repertoire of east Australian humpback whales was investigated from 1997, 2003-2004, and 2008. Out of 46 qualitatively defined call types, 19 were classified as "song-unit calls" that tended to change with the song, and 15 were "inconsistent" and only found in one or two years. Twelve call types were "stable" and present in all years and were commonly produced (64.2% of calls). Stable calls tended to vary in some of the measured call parameters but there was no clear trend between years. This result could indicate that minor changes to calls are not permanent, but reflect individual differences in call production or the graded nature of calls within different social environments. This research has clearly identified stable calls in the call repertoire of humpback whales and while their function is not well understood, their stability suggests an important role in social interactions.

  11. Robust stability analysis for Markovian jumping stochastic neural networks with mode-dependent time-varying interval delay and multiplicative noise

    Institute of Scientific and Technical Information of China (English)

    Zhang Hua-Guang; Fu Jie; Ma Tie-Dong; Tong Shao-Cheng

    2009-01-01

    This paper is concerned with the problem of robust stability for a class of Markovian jumping stochastic neural networks (MJSNNs) subject to mode-dependent time-varying interval delay and state-multiplicative noise.Based on the Lyapunov-Krasovskii functional and a stochastic analysis approach,some new delay-dependent sufficient conditions are obtained in the linear matrix inequality (LMI) format such that delayed MJSNNs are globally asymptotically stable in the mean-square sense for all admissible uncertainties.An important feature of the results is that the stability criteria are dependent on not only the lower bound and upper bound of delay for all modes but also the covariance matrix consisting of the correlation coefficient.Numerical examples are given to illustrate the effectiveness.

  12. In silico analysis of the cyclophilin repertoire of apicomplexan parasites

    Directory of Open Access Journals (Sweden)

    von Samson-Himmelstjerna Georg

    2009-06-01

    Full Text Available Abstract Background Cyclophilins (Cyps are peptidyl cis/trans isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary. Results BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of Cryptosporidium hominis, Toxoplasma gondii, Plasmodium falciparum, Theileria annulata, Theileria parva, and Babesia bovis. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7–9 for Cryptosporidia and 14 for T. gondii. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing. Conclusion The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.

  13. Minimum Alveolar Concentration Needed to Block Adrenergic Response of Sevoflurane with Nitrous Oxide Varies Depending on the Stimulation Sites in Adult Surgical Patients

    Directory of Open Access Journals (Sweden)

    Tetsu Kimura

    2015-02-01

    Full Text Available Background We examined whether minimum alveolar anesthetic concentration needed to block adrenergic response (MAC-BAR of sevoflurane with nitrous oxide (N2O varies depending on body surface sites to which noxious stimuli are applied. Methods Seventy-seven ASA I adult patients, aged 18-50 years old, were anesthetized with sevoflurane and 66% N2O in O2, and their tracheas were intubated. The anesthesia was maintained with 66% N2O in O2 plus sevoflurane at predetermined end-tidal concentrations (0.8, 1.1, 1.4, 1.7, 2.0, 2.3, or 2.6%, n = 11 in each concentration for at least 15 minutes. Heart rate (HR and non-invasive blood pressure (BP was recorded at 1-minute interval automatically. As a noxious stimulus, electrical tetanic stimulation with a 15 sec burst of 50 Hz, 0.25 msec square-wave, 55 mA electric current was applied at three different sites; forehead, abdomen, or thigh. A positive cardiovascular response was defined as an increase of either mean BP or HR by more than 15% from the pre-stimulation value. Logistic regression analysis was used to determine MAC-BAR. Results MAC-BAR of sevoflurane with 66% N2O obtained by stimulating forehead, abdomen, and thigh were 2.01% (95% CI: 1.70-2.57%, 1.71% (1.13-2.74%, and 1.31% (0.77-1.66%, respectively. MAC-BAR on the forehead was significantly higher than that on the thigh. Conclusion MAC-BAR of sevoflurane with 66% N2O varied depending on the body surface sites to which noxious stimuli were applied. These findings support our clinical impression that sensitivities to pain vary among body surface sites, and that anesthetic requirement to stabilize hemodynamic variables vary among surgical sites.

  14. Flexible knowledge repertoires: communication by leaders in trauma teams

    Directory of Open Access Journals (Sweden)

    Jacobsson Maritha

    2012-07-01

    Full Text Available Abstract Background In emergency situations, it is important for the trauma team to efficiently communicate their observations and assessments. One common communication strategy is “closed-loop communication”, which can be described as a transmission model in which feedback is of great importance. The role of the leader is to create a shared goal in order to achieve consensus in the work for the safety of the patient. The purpose of this study was to analyze how formal leaders communicate knowledge, create consensus, and position themselves in relation to others in the team. Methods Sixteen trauma teams were audio- and video-recorded during high fidelity training in an emergency department. Each team consisted of six members: one surgeon or emergency physician (the designated team leader, one anaesthesiologist, one nurse anaesthetist, one enrolled nurse from the theatre ward, one registered nurse and one enrolled nurse from the emergency department (ED. The communication was transcribed and analyzed, inspired by discourse psychology and Strauss’ concept of “negotiated order”. The data were organized and coded in NVivo 9. Results The findings suggest that leaders use coercive, educational, discussing and negotiating strategies to work things through. The leaders in this study used different repertoires to convey their knowledge to the team, in order to create a common goal of the priorities of the work. Changes in repertoires were dependent on the urgency of the situation and the interaction between team members. When using these repertoires, the leaders positioned themselves in different ways, either on an authoritarian or a more egalitarian level. Conclusion This study indicates that communication in trauma teams is complex and consists of more than just transferring messages quickly. It also concerns what the leaders express, and even more importantly, how they speak to and involve other team members.

  15. New results on delay-range-dependent stability analysis for interval time-varying delay systems with non-linear perturbations.

    Science.gov (United States)

    Liu, Pin-Lin

    2015-07-01

    This paper studies the problem of the stability analysis of interval time-varying delay systems with nonlinear perturbations. Based on the Lyapunov-Krasovskii functional (LKF), a sufficient delay-range-dependent criterion for asymptotic stability is derived in terms of linear matrix inequality (LMI) and integral inequality approach (IIA) and delayed decomposition approach (DDA). Further, the delay range is divided into two equal segments for stability analysis. Both theoretical and numerical comparisons have been provided to show the effectiveness and efficiency of the present method. Two well-known examples are given to show less conservatism of our obtained results and the effectiveness of the proposed method.

  16. Finite-time H∞ control for a class of Markovian jump systems with mode-dependent time-varying delays via new Lyapunov functionals.

    Science.gov (United States)

    Cheng, Jun; Zhu, Hong; Zhong, Shouming; Zeng, Yong; Dong, Xiucheng

    2013-11-01

    This paper is concerned with the problem of finite-time H∞ control for a class of Markovian jump systems with mode-dependent time-varying delays via new Lyapunov functionals. In order to reduce conservatism, a new Lyapunov-Krasovskii functional is constructed. Based on the derived condition, the reliable H∞ control problem is solved, and the system trajectory stays within a prescribed bound during a specified time interval. Finally, numerical examples are given to demonstrate the proposed approach is more effective than some existing ones.

  17. Repertoire and frequency of consumption in wine

    DEFF Research Database (Denmark)

    Chrysochou, Polymeros; Krystallis, Athanasios

    Frequency of consumption has always been an important criterion for characterising and segmenting buyers. The aim of this paper is to provide a deeper understanding of the repertoire and loyalty structures between heavy and light wine buyers. Based on a study conducted with stated preference data......, basic brand performance measures are estimated through Juster purchase probabilities of brand choice. The polarisation index f (phi) is used as a measure to model loyalty. Results show that light buyers have a wider repertoire than heavy buyers, buying more small brands. In terms of loyalty, heavy...... buyers are more loyalty prone than light buyers, both as regards the brand name and the wine attributes examined in this study....

  18. The human IgE repertoire.

    Science.gov (United States)

    Gadermaier, Elisabeth; Levin, Mattias; Flicker, Sabine; Ohlin, Mats

    2014-01-01

    IgE is a key mediator in allergic diseases. However, in strong contrast to other antibody isotypes, many details of the composition of the human IgE repertoire are poorly defined. The low levels of human IgE in the circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review, we summarize the current knowledge on these repertoires both in terms of their complexity and activity, i.e. knowledge which despite the difficulties encountered when studying the molecular details of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allow the isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the context of human disease in the years to come.

  19. The porcine antibody repertoire: Variations on the textbook theme

    Directory of Open Access Journals (Sweden)

    John eButler

    2012-06-01

    Full Text Available The genes encoding the heavy and light chains of swine antibodies are organized in the same manner as in other eutherian mammals. There are ~ 30 VH genes, two functional DH genes and one functional JH gene. There are 14-60 V genes and 5 J segments, >22V genes and at least four JC cassettes. The heavy chain constant regions encode the same repertoire of isotypes common to other eutherian mammals. The piglet models offers advantage over rodent models since the fetal repertoire develops without maternal influences and the precocial nature of their multiple offspring allows the experimenter to control the influences of environmental and maternal factors on repertoire development postnatally. B cell lymphogenesis in swine begins in the fetal yolk sac at 20 days of gestation (DG, moves to the fetal liver at 30 DG and eventually to the bone marrow which dominates until birth (114 DG and to at least 5 weeks postpartum. There is no evidence that the ileal Peyers patches are a site of B cell lymphogenesis or are required for B cell maintenance. Unlike rodents and humans, light chain rearrangement begins first in the lambda locus; kappa rearrangements are not seen until late gestation.Dissimilar to lab rodents and more in the direction of the rabbit, swine utilize a small number of VH genes to form >90% of their pre-immune repertoire. Diversification in response to environmental antigen does not alter this pattern and is achieved by somatic hypermutation (SHM of the same small number of VH genes. The situation for light chains is less-well studied, but certain V and J and V and J are dominant in transcripts. The transcribed and secreted pre-immune antibodies of the fetus include mainly IgM, IgA and IgG3; this last isotype may provide a type of first responder mucosal immunity. Development of functional adaptive immunity is dependent on bacterial PAMPs or PAMPs provided by viral infections, indicating the importance of innate

  20. Repertoire and frequency of consumption in wine

    DEFF Research Database (Denmark)

    Chrysochou, Polymeros; Krystallis, Athanasios

    Frequency of consumption has always been an important criterion for characterising and segmenting buyers. The aim of this paper is to provide a deeper understanding of the repertoire and loyalty structures between heavy and light wine buyers. Based on a study conducted with stated preference data...... buyers are more loyalty prone than light buyers, both as regards the brand name and the wine attributes examined in this study....

  1. Characterization of the sortase repertoire in Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Willy Aucher

    Full Text Available LPXTG proteins, present in most if not all Gram-positive bacteria, are known to be anchored by sortases to the bacterial peptidoglycan. More than one sortase gene is often encoded in a bacterial species, and each sortase is supposed to specifically anchor given LPXTG proteins, depending of the sequence of the C-terminal cell wall sorting signal (cwss, bearing an LPXTG motif or another recognition sequence. B. anthracis possesses three sortase genes. B. anthracis sortase deleted mutant strains are not affected in their virulence. To determine the sortase repertoires, we developed a genetic screen using the property of the gamma phage to lyse bacteria only when its receptor, GamR, an LPXTG protein, is exposed at the surface. We identified 10 proteins that contain a cell wall sorting signal and are covalently anchored to the peptidoglycan. Some chimeric proteins yielded phage lysis in all sortase mutant strains, suggesting that cwss proteins remained surface accessible in absence of their anchoring sortase, probably as a consequence of membrane localization of yet uncleaved precursor proteins. For definite assignment of the sortase repertoires, we consequently relied on a complementary test, using a biochemical approach, namely immunoblot experiments. The sortase anchoring nine of these proteins has thus been determined. The absence of virulence defect of the sortase mutants could be a consequence of the membrane localization of the cwss proteins.

  2. T Cell Repertoire and Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Kenneth Croitoru

    1996-01-01

    Full Text Available The diversity of the T cell receptor repertoire is generated through rearrangement of the variable, junctional and constant region genes. Selection processes in the thymus and periphery serve to eliminate self-reacting T cells, thereby preventing autoimmune disease. The possibility that inflammatory bowel disease (IBD is an autoimmune disease has led to the search for an auto-antigen. In addition, studies are exploring the T cell receptor repertoire in IBD patients for changes that may provide clues regarding etiopathogenesis. Using monoclonal antibodies to T cell receptor variable-gene products or polymerase chain reaction analysis of variable-gene mRNA expression, the mucosal T cell repertoire has been examined in humans. The intestinal intraepithelial lymphocytes show a significant degree of oligoclonal expansion that may represent local antigen exposure or unique selection processes. This is in keeping with studies that show that murine intestinal intraepithelial lymphocytes undergo positive and possibly negative selection independent of the thymus. In the inflamed human gut, shifts in the T cell receptor repertoire may also reflect recruitment of peripheral T cells to the gut. In one study, a subset of Crohn’s disease patients was shown to have an increase in the proportion of variable β8 peripheral blood lymphocyte and mesenteric lymph node cells, suggesting a superantigen effect. The authors hypothesized that changes in the functional T cell receptor repertoire can also occur which might be independent of changes in the distribution of T cells expressing variable β T cell receptors. In fact, the authors have shown there is a selective decrease in the cytotoxic function of peripheral variable β8 T cells in Crohn’s disease. Furthermore, stimulation with the variable β8 selective bacterial enterotoxin staphylococcal enterotoxin E failed to increase the cytotoxic function in this subset of Crohn’s disease patients compared with

  3. Observer-based robust finite time H∞ sliding mode control for Markovian switching systems with mode-dependent time-varying delay and incomplete transition rate.

    Science.gov (United States)

    Gao, Lijun; Jiang, Xiaoxiao; Wang, Dandan

    2016-03-01

    This paper investigates the problem of robust finite time H∞ sliding mode control for a class of Markovian switching systems. The system is subjected to the mode-dependent time-varying delay, partly unknown transition rate and unmeasurable state. The main difficulty is that, a sliding mode surface cannot be designed based on the unknown transition rate and unmeasurable state directly. To overcome this obstacle, the set of modes is firstly divided into two subsets standing for known transition rate subset and unknown one, based on which a state observer is established. A component robust finite-time sliding mode controller is also designed to cope with the effect of partially unknown transition rate. It is illustrated that the reachability, finite-time stability, finite-time boundedness, finite-time H∞ state feedback stabilization of sliding mode dynamics can be ensured despite the unknown transition rate. Finally, the simulation results verify the effectiveness of robust finite time control problem.

  4. Propagation and interaction of matter-wave solitons in Bose-Einstein condensates with time-dependent scattering length and varying potentials

    Energy Technology Data Exchange (ETDEWEB)

    Li Biao; Li Yuqi [Nonlinear Science Center, Ningbo University, Ningbo 315211 (China); Zhang Xiaofei; Liu, W M, E-mail: biaolee2000@yahoo.com.cn [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China)

    2011-09-14

    We present two families of one-soliton solutions and three families of two-soliton solutions for a generalized nonlinear Schroedinger equation, which is characterized by the time-dependent scattering length and varying potentials. Then, we investigate the propagation of one-soliton and interactions of two-soliton by some selected control functions. The results show that the intensities of one- and two-soliton first increase rapidly to a peak value, and then decay very slowly to the background value; thus, the lifetimes of both one-soliton and two-soliton in Bose-Einstein condensates can be extended largely at least to the order of the lifetime of a Bose-Einstein condensate in real experiments. Our results open up new ways of considerable experimental interest for the management of matter-wave solitons in Bose-Einstein condensates.

  5. Intrinsic variability in Pv, RRP size, Ca2+ channel repertoire and presynaptic potentiation in individual synaptic boutons

    Directory of Open Access Journals (Sweden)

    Pablo eAriel

    2013-01-01

    Full Text Available The strength of individual synaptic contacts is considered a key modulator of information flow across circuits. Presynaptically the strength can be parsed into two key parameters: the size of the readily-releasable pool (RRP and the probability that a vesicle in that pool will undergo exocytosis when an action potential fires (Pv. How these variables are controlled and the degree to which they vary across individual nerve terminals is crucial to understand synaptic plasticity within neural circuits. Here we report robust measurements of these parameters in rat hippocampal neurons and their variability across populations of individual synapses. We explore the diversity of presynaptic Ca2+ channel repertoires and evaluate their effect on synaptic strength at single boutons. Finally, we study the degree to which synapses can be differentially modified by a known potentiator of presynaptic function, forskolin. Our experiments revealed that both Pv and RRP spanned a large range, even for synapses made by the same axon, demonstrating that presynaptic efficacy is governed locally at the single synapse level. Synapses varied greatly in their dependence on N or P/Q type Ca2+ channels for neurotransmission, but there was no association between specific channel repertoires and synaptic efficacy. Increasing cAMP concentration using forskolin enhanced synaptic transmission in a Ca2+-independent manner that was inversely related with a synapse’s initial Pv, and independent of its RRP size. We propose a simple model based on the relationship between Pv and calcium entry that can account for the variable potentiation of synapses based on initial probability of vesicle fusion.

  6. Structural and genetic diversity in antibody repertoires from diverse species.

    Science.gov (United States)

    de los Rios, Miguel; Criscitiello, Michael F; Smider, Vaughn V

    2015-08-01

    The antibody repertoire is the fundamental unit that enables development of antigen specific adaptive immune responses against pathogens. Different species have developed diverse genetic and structural strategies to create their respective antibody repertoires. Here we review the shark, chicken, camel, and cow repertoires as unique examples of structural and genetic diversity. Given the enormous importance of antibodies in medicine and biological research, the novel properties of these antibody repertoires may enable discovery or engineering of antibodies from these non-human species against difficult or important epitopes.

  7. The odorant receptor repertoire of teleost fish

    Directory of Open Access Journals (Sweden)

    Alioto Tyler S

    2005-12-01

    Full Text Available Abstract Background Vertebrate odorant receptors comprise three types of G protein-coupled receptors: the OR, V1R and V2R receptors. The OR superfamily contains over 1,000 genes in some mammalian species, representing the largest gene superfamily in the mammalian genome. Results To facilitate an informed analysis of OR gene phylogeny, we identified the complete set of 143 OR genes in the zebrafish genome, as well as the OR repertoires in two pufferfish species, fugu (44 genes and tetraodon (42 genes. Although the genomes analyzed here contain fewer genes than in mammalian species, the teleost OR genes can be grouped into a larger number of major clades, representing greater overall OR diversity in the fish. Conclusion Based on the phylogeny of fish and mammalian repertoires, we propose a model for OR gene evolution in which different ancestral OR genes or gene families were selectively lost or expanded in different vertebrate lineages. In addition, our calculations of the ratios of non-synonymous to synonymous codon substitutions among more recently expanding OR subgroups in zebrafish implicate residues that may be involved in odorant binding.

  8. The vocal repertoire of adult and neonate giant otters (Pteronura brasiliensis.

    Directory of Open Access Journals (Sweden)

    Christina A S Mumm

    Full Text Available Animals use vocalizations to exchange information about external events, their own physical or motivational state, or about individuality and social affiliation. Infant babbling can enhance the development of the full adult vocal repertoire by providing ample opportunity for practice. Giant otters are very social and frequently vocalizing animals. They live in highly cohesive groups, generally including a reproductive pair and their offspring born in different years. This basic social structure may vary in the degree of relatedness of the group members. Individuals engage in shared group activities and different social roles and thus, the social organization of giant otters provides a basis for complex and long-term individual relationships. We recorded and analysed the vocalizations of adult and neonate giant otters from wild and captive groups. We classified the adult vocalizations according to their acoustic structure, and described their main behavioural context. Additionally, we present the first description of vocalizations uttered in babbling bouts of new born giant otters. We expected to find 1 a sophisticated vocal repertoire that would reflect the species' complex social organisation, 2 that giant otter vocalizations have a clear relationship between signal structure and function, and 3 that the vocal repertoire of new born giant otters would comprise age-specific vocalizations as well as precursors of the adult repertoire. We found a vocal repertoire with 22 distinct vocalization types produced by adults and 11 vocalization types within the babbling bouts of the neonates. A comparison within the otter subfamily suggests a relation between vocal and social complexity, with the giant otters being the socially and vocally most complex species.

  9. Varying Constants

    CERN Document Server

    Damour, Thibault Marie Alban Guillaume

    2003-01-01

    We review some string-inspired theoretical models which incorporate a correlated spacetime variation of coupling constants while remaining naturally compatible both with phenomenological constraints coming from geochemical data (Oklo; Rhenium decay) and with present equivalence principle tests. Barring unnatural fine-tunings of parameters, a variation of the fine-structure constant as large as that recently ``observed'' by Webb et al. in quasar absorption spectra appears to be incompatible with these phenomenological constraints. Independently of any model, it is emphasized that the best experimental probe of varying constants are high-precision tests of the universality of free fall, such as MICROSCOPE and STEP. Recent claims by Bekenstein that fine-structure-constant variability does not imply detectable violations of the equivalence principle are shown to be untenable.

  10. Microbial community responses to 17 years of altered precipitation are seasonally dependent and coupled to co-varying effects of water content on vegetation and soil C

    Science.gov (United States)

    Sorensen, Patrick O.; Germino, Matthew J.; Feris, Kevin P.

    2013-01-01

    Precipitation amount and seasonal timing determine the duration and distribution of water available for plant and microbial activity in the cold desert sagebrush steppe. In this study, we sought to determine if a sustained shift in the amount and timing of precipitation would affect soil microbial diversity, community composition, and soil carbon (C) storage. Field plots were irrigated (+200 mm) during the dormant or growing-season for 17 years. Microbial community responses were assessed over the course of a year at two depths (15–20 cm, 95–100 cm) by terminal restriction fragment length polymorphism (T-RFLP), along with co-occurring changes in plant cover and edaphic properties. Bacterial richness, Shannon Weaver diversity, and composition in shallow soils (15–20 cm) as well as evenness in deep soils (95–100 cm) differed across irrigation treatments during July. Irrigation timing affected fungal community diversity and community composition during the dormant season and most strongly in deep soils (95–100 cm). Dormant-season irrigation increased the ratio of shrubs to forbs and reduced soil C in shallow soils by 16% relative to ambient conditions. It is unclear whether or not soil C will continue to decline with continued treatment application or if microbial adaptation could mitigate sustained soil C losses. Future changes in precipitation timing will affect soil microbes in a seasonally dependent manner and be coupled to co-varying effects of water content on vegetation and soil C.

  11. VH replacement in primary immunoglobulin repertoire diversification.

    Science.gov (United States)

    Sun, Amy; Novobrantseva, Tatiana I; Coffre, Maryaline; Hewitt, Susannah L; Jensen, Kari; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B

    2015-02-01

    The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.

  12. Personal receptor repertoires: olfaction as a model

    Directory of Open Access Journals (Sweden)

    Olender Tsviya

    2012-08-01

    Full Text Available Abstract Background Information on nucleotide diversity along completely sequenced human genomes has increased tremendously over the last few years. This makes it possible to reassess the diversity status of distinct receptor proteins in different human individuals. To this end, we focused on the complete inventory of human olfactory receptor coding regions as a model for personal receptor repertoires. Results By performing data-mining from public and private sources we scored genetic variations in 413 intact OR loci, for which one or more individuals had an intact open reading frame. Using 1000 Genomes Project haplotypes, we identified a total of 4069 full-length polypeptide variants encoded by these OR loci, average of ~10 per locus, constituting a lower limit for the effective human OR repertoire. Each individual is found to harbor as many as 600 OR allelic variants, ~50% higher than the locus count. Because OR neuronal expression is allelically excluded, this has direct effect on smell perception diversity of the species. We further identified 244 OR segregating pseudogenes (SPGs, loci showing both intact and pseudogene forms in the population, twenty-six of which are annotatively “resurrected” from a pseudogene status in the reference genome. Using a custom SNP microarray we validated 150 SPGs in a cohort of 468 individuals, with every individual genome averaging 36 disrupted sequence variations, 15 in homozygote form. Finally, we generated a multi-source compendium of 63 OR loci harboring deletion Copy Number Variations (CNVs. Our combined data suggest that 271 of the 413 intact OR loci (66% are affected by nonfunctional SNPs/indels and/or CNVs. Conclusions These results portray a case of unusually high genetic diversity, and suggest that individual humans have a highly personalized inventory of functional olfactory receptors, a conclusion that might apply to other receptor multigene families.

  13. The adolescent behavioral repertoire: its latent structure in the PACARDO region of Latin America.

    Science.gov (United States)

    Chen, Chuan-Yu; Dormitzer, Catherine M; Bejarano, Julio; Caris, Luis H; Bolivar Diaz, Jorge; Sanchez, Mauricio; Vittetoe, Kenneth; Anthony, James C

    2004-01-01

    In this study, the authors probed the latent structure of the adolescent behavioral repertoire (ABR) and estimated its sociodemographic correlates. The authors drew a nationally representative sample of 12,797 school-attending youth from the 7 countries in the PACARDO region of Latin America: Panama, Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, and the Dominican Republic. On the basis of the Behavioral Repertoire Self Report scale (Johanson, Duffy, and Anthony, 1996), the authors identified 5 primary dimensions, including religious behaviors, socializing, sports, home-based activities, and gender socialization activities. The authors found that the levels of involvement in these dimensions of the ABR varied across sociodemographic characteristics. The observed multidimensional structure of the ABR sets the stage for future research on adolescent health in relation to these behaviors and activities.

  14. FoxO-dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension.

    Science.gov (United States)

    Brocca, Lorenza; Toniolo, Luana; Reggiani, Carlo; Bottinelli, Roberto; Sandri, Marco; Pellegrino, Maria Antonietta

    2017-02-15

    Muscle atrophy is a debilitating condition that affects a high percentage of the population with a negative impact on quality of life. Dissecting the molecular level of the atrophy process, and the similarities/dissimilarities among different catabolic conditions, is a necessary step for designing specific countermeasures to attenuate/prevent muscle loss. The FoxO family transcription factors represent one of the most important regulators of atrophy programme stimulating the expression of many atrophy-related genes. The findings of the present study clearly indicate that the signalling network controlling the atrophy programme is specific for each catabolic condition. Muscle atrophy is a complex process that is in common with many different catabolic diseases including disuse/inactivity and ageing. The signalling pathways that control the atrophy programme in the different disuse/inactivity conditions have not yet been completely dissected. The inhibition of FoxO is considered to only partially spare muscle mass after denervation. The present study aimed: (i) to determine the involvement of FoxOs in hindlimb suspension disuse model; (ii) to define whether the molecular events of protein breakdown are shared among different unloaded muscles; and finally (iii) to compare the data obtained in this model with another model of inactivity such as denervation. Both wild-type and muscle-specific FoxO1,3,4 knockout (FoxO1,3,4(-/-) ) mice were unloaded for 3 and 14 days and muscles were characterized by functional, morphological, biochemical and molecular assays. The data obtained show that FoxOs are required for muscle loss and force drop during unloading. Moreover, we found that FoxO-dependent atrogenes vary in different unloaded muscles and that they diverge from denervation. The findings of the present study clearly indicate that the signalling network that controls the atrophy programme is specific for each catabolic condition. © 2016 The Authors. The Journal of

  15. Degree of multicollinearity and variables involved in linear dependence in additive-dominant models Grau de multicolinearidade e variáveis envolvidas na dependência linear em modelos aditivo-dominantes

    Directory of Open Access Journals (Sweden)

    Juliana Petrini

    2012-12-01

    Full Text Available The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567, yearling weight (n=58,124, and scrotal circumference (n=20,371 of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.O objetivo deste trabalho foi avaliar o grau de multicolinearidade e identificar as variáveis envolvidas na dependência linear em modelos aditivo-dominantes. Foram utilizados dados de peso ao nascimento (n=141.567, peso ao ano (n=58.124 e perímetro escrotal (n=20.371 de bovinos de corte compostos Montana Tropical. O diagnóstico de multicolinearidade foi baseado no fator de inflação de variância (VIF e no exame dos índices de condição e dos autovalores da matriz de correlações entre as variáveis explanatórias. O primeiro modelo estudado (RM incluiu o efeito fixo de classe de idade da mãe ao parto e

  16. Effectiveness of Prompts on Fourth-Grade Children’s Dietary Recall Accuracy Depends on Retention Interval and Varies by Gender1234

    Science.gov (United States)

    Baxter, Suzanne D; Smith, Albert F; Hitchcock, David B; Guinn, Caroline H; Royer, Julie A; Collins, Kathleen L; Smith, Alyssa L; Puryear, Megan P; Vaadi, Kate K; Finney, Christopher J; Miller, Patricia H

    2015-01-01

    , although the effectiveness of different prompts depends on RI and varies by gender: at a short RI, the choice of prompts has little systematic effect on accuracy, whereas at a long RI, reverse prompts may elicit the most accurate recalls. PMID:26224752

  17. Delay-Range-Dependent Global Robust Passivity Analysis of Discrete-Time Uncertain Recurrent Neural Networks with Interval Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Chien-Yu Lu

    2009-01-01

    Full Text Available This paper examines a passivity analysis for a class of discrete-time recurrent neural networks (DRNNs with norm-bounded time-varying parameter uncertainties and interval time-varying delay. The activation functions are assumed to be globally Lipschitz continuous. Based on an appropriate type of Lyapunov functional, sufficient passivity conditions for the DRNNs are derived in terms of a family of linear matrix inequalities (LMIs. Two numerical examples are given to illustrate the effectiveness and applicability.

  18. Immunoglobulins, antibody repertoire and B cell development.

    Science.gov (United States)

    Butler, J E; Zhao, Y; Sinkora, M; Wertz, N; Kacskovics, I

    2009-03-01

    Swine share with most placental mammals the same five antibody isotypes and same two light chain types. Loci encoding lambda, kappa and Ig heavy chains appear to be organized as they are in other mammals. Swine differ from rodents and primates, but are similar to rabbits in using a single VH family (VH3) to encode their variable heavy chain domain, but not the family used by cattle, another artiodactyl. Distinct from other hoofed mammals and rodents, Ckappa:Clambda usage resembles the 1:1 ratio seen in primates. Since IgG subclasses diversified after speciation, same name subclass homologs do not exist among swine and other mammals unless very closely related. Swine possess six putative IgG subclasses that appear to have diversified by gene duplication and exon shuffle while retaining motifs that can bind to FcgammaRs, FcRn, C1q, protein A and protein G. The epithelial chorial placenta of swine and the precosial nature of their offspring have made piglets excellent models for studies on fetal antibody repertoire development and on the postnatal role of gut colonization, maternal colostrum and neonatal infection on the development of adaptive immunity during the "critical window" of immunological development. This chapter traces the study of the humoral immune system of this species through its various eras of discovery and compiles the results in tables and figures that should be a useful reference for educators and investigators.

  19. Enthusiastic, realistic and critical: discourses of Internet use in the context of everyday life information seeking Internet, Everyday life, Information seeking, Discourse analysis, Interpretative repertoires, Information sources, Value, Use

    Directory of Open Access Journals (Sweden)

    Reijo Savolainen

    2004-01-01

    Full Text Available Based on the interviews of 18 participants, the ways in which people talk about their source preferences with regard to the Internet in everyday life information seeking were investigated by using discourse analysis. Three major interpretative repertoires were identified: Enthusiastic, Realistic and Critical. The Enthusiastic repertoire emphasizes the strengths of the Internet, conceiving it as a 'great enabler' or as a 'technology of freedom'. In this repertoire, positive expressions such as fast, easy and interactive are favoured. In the Realistic repertoire, the source preferences are constructed as situation-bound choices. The Internet is given no absolute priority but its value is seen to depend on the relative advantages in specific situations. No sources or channels are superior by themselves but their value is contingent on the use situation and its specific requirements. Finally, the Critical repertoire is characterized by a reserved standpoint to the advantages brought by the Internet. Central to this repertoire is the critical view on the low amount of relevant informationavailable in the Internet and the poor organization of networked information, rendering effective information seeking difficult. Due to their ideal-typical nature, the above repertoires are rather independent. However, in the everyday discursive practices, the repertoires are used alternately, and the same speaker may shift from one repertoire to another within the same account.

  20. Novel underwater soundscape: acoustic repertoire of plainfin midshipman fish.

    Science.gov (United States)

    McIver, Eileen L; Marchaterre, Margaret A; Rice, Aaron N; Bass, Andrew H

    2014-07-01

    Toadfishes are among the best-known groups of sound-producing (vocal) fishes and include species commonly known as toadfish and midshipman. Although midshipman have been the subject of extensive investigation of the neural mechanisms of vocalization, this is the first comprehensive, quantitative analysis of the spectro-temporal characters of their acoustic signals and one of the few for fishes in general. Field recordings of territorial, nest-guarding male midshipman during the breeding season identified a diverse vocal repertoire composed of three basic sound types that varied widely in duration, harmonic structure and degree of amplitude modulation (AM): 'hum', 'grunt' and 'growl'. Hum duration varied nearly 1000-fold, lasting for minutes at a time, with stable harmonic stacks and little envelope modulation throughout the sound. By contrast, grunts were brief, ~30-140 ms, broadband signals produced both in isolation and repetitively as a train of up to 200 at intervals of ~0.5-1.0 s. Growls were also produced alone or repetitively, but at variable intervals of the order of seconds with durations between those of grunts and hums, ranging 60-fold from ~200 ms to 12 s. Growls exhibited prominent harmonics with sudden shifts in pulse repetition rate and highly variable AM patterns, unlike the nearly constant AM of grunt trains and flat envelope of hums. Behavioral and neurophysiological studies support the hypothesis that each sound type's unique acoustic signature contributes to signal recognition mechanisms. Nocturnal production of these sounds against a background chorus dominated constantly for hours by a single sound type, the multi-harmonic hum, reveals a novel underwater soundscape for fish. © 2014. Published by The Company of Biologists Ltd.

  1. Ontogeny of the avian intestinal immunoglobulin repertoire : Modification in CDR3 length and conserved VH-pseudogene usage

    NARCIS (Netherlands)

    den Hartog, Gerco; Crooijmans, Richard P. M. A.; Parmentier, Henk K.; Savelkoul, Huub F. J.; Bos, Nicolaas A.; Lammers, Aart

    2013-01-01

    Immunoglobulins play an important role in maintenance of mucosal homeostasis in the gut. The antigen binding specificity of these immunoglobulins depends for a large part on the hypervariable CDR3 region. To gain knowledge about isotype-specific development of the CDR3 repertoire we examined CDR3 sp

  2. Ontogeny of the avian intestinal immunoglobulin repertoire: Modification in CDR3 length and conserved VH-pseudogene usage

    NARCIS (Netherlands)

    Hartog, den C.G.; Crooijmans, R.P.M.A.; Parmentier, H.K.; Savelkoul, H.F.J.; Bos, N.A.; Lammers, A.

    2013-01-01

    Immunoglobulins play an important role in maintenance of mucosal homeostasis in the gut. The antigen binding specificity of these immunoglobulins depends for a large part on the hypervariable CDR3 region. To gain knowledge about isotype-specific development of the CDR3 repertoire we examined CDR3 sp

  3. Inferring processes underlying B-cell repertoire diversity

    Science.gov (United States)

    Elhanati, Yuval; Sethna, Zachary; Marcou, Quentin; Callan, Curtis G.; Mora, Thierry; Walczak, Aleksandra M.

    2015-01-01

    We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, owing to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site. PMID:26194757

  4. Rapid evolution of the sequences and gene repertoires of secreted proteins in bacteria.

    Directory of Open Access Journals (Sweden)

    Teresa Nogueira

    Full Text Available Proteins secreted to the extracellular environment or to the periphery of the cell envelope, the secretome, play essential roles in foraging, antagonistic and mutualistic interactions. We hypothesize that arms races, genetic conflicts and varying selective pressures should lead to the rapid change of sequences and gene repertoires of the secretome. The analysis of 42 bacterial pan-genomes shows that secreted, and especially extracellular proteins, are predominantly encoded in the accessory genome, i.e. among genes not ubiquitous within the clade. Genes encoding outer membrane proteins might engage more frequently in intra-chromosomal gene conversion because they are more often in multi-genic families. The gene sequences encoding the secretome evolve faster than the rest of the genome and in particular at non-synonymous positions. Cell wall proteins in Firmicutes evolve particularly fast when compared with outer membrane proteins of Proteobacteria. Virulence factors are over-represented in the secretome, notably in outer membrane proteins, but cell localization explains more of the variance in substitution rates and gene repertoires than sequence homology to known virulence factors. Accordingly, the repertoires and sequences of the genes encoding the secretome change fast in the clades of obligatory and facultative pathogens and also in the clades of mutualists and free-living bacteria. Our study shows that cell localization shapes genome evolution. In agreement with our hypothesis, the repertoires and the sequences of genes encoding secreted proteins evolve fast. The particularly rapid change of extracellular proteins suggests that these public goods are key players in bacterial adaptation.

  5. The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells.

    Science.gov (United States)

    Yuksel, Aytac; Bildik, Gamze; Senbabaoglu, Filiz; Akin, Nazli; Arvas, Macit; Unal, Fehmi; Kilic, Yagmur; Karanfil, Isil; Eryılmaz, Baldan; Yilmaz, Pelin; Ozkanbaş, Can; Taskiran, Cagatay; Aksoy, Senai; Guzel, Yılmaz; Balaban, Basak; Ince, Umit; Iwase, Akira; Urman, Bulent; Oktem, Ozgur

    2015-12-01

    groups of 13 to receive a single IP injection of: saline (control), gemcitabine (200 mg/kg), cisplatin (50 mg/kg) or cyclophosphamide (200 mg/kg). The animals were euthanized 72 h later. Follicle counts and serum AMH levels were compared between the groups. In vitro cytotoxicity studies were performed using mitotic non-luteinized rat (SIGC) and human (COV434, HGrC1) granulosa cells, and non-mitotic luteinized human (HLGC) granulosa cells. The cells were plated at a density of 5000 cells/well using DMEM-F12 culture media supplemented with 10% FBS. Chemotherapy agents were used at their therapeutic blood concentrations. The growth of mitotic granulosa cells was monitored real-time using xCelligence system. Live/dead cell and apoptosis assays were also carried out using intravital Yo-Pro-1 staining and cleaved caspase-3 expression, respectively. Estradiol (E2), progesterone (P) and anti-Mullerian hormone (AMH) levels were assayed with ELISA. Cyclophosphamide and cisplatin caused massive atresia of both primordials and growing follicles in the rat ovary whereas gemcitabine impacted pre-antral/antral follicles only. Cyclophosphamide and cisplatin induced apoptosis of both mitotic non-luteinized and non-mitotic luteinized granulosa cells in vitro. By contrast, cytotoxicity of gemcitabine was confined to mitotic non-luteinized granulosa cells. This study tested only three chemotherapeutic agents. The experimental methodology described here could be applied to other drugs for detailed analysis of their ovarian cytotoxicity. These findings indicate that in vivo and in vitro cytotoxic actions of chemotherapy drugs on the ovarian follicles and granulosa cells vary depending upon the their mechanism of action and the nature of the granulosa cells. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Dopamine receptor repertoire of human granulosa cells

    Directory of Open Access Journals (Sweden)

    Kunz Lars

    2007-10-01

    Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

  7. Thinking through Text Comprehension III: The Programing of Verbal and Investigative Repertoires

    Science.gov (United States)

    Leon, Marta; Layng, T. V. Joe; Sota, Melinda

    2011-01-01

    Reading comprehension can be considered a complex human performance involving two integrated repertoires: a verbal repertoire and an investigative (generative) repertoire. The analytical and reasoning skills necessary to demonstrate reading comprehension can be systematically taught by analyzing the verbal and investigative repertoires involved…

  8. Degeneracy-driven self-structuring dynamics in selective repertoires.

    Science.gov (United States)

    Atamas, Sergei P; Bell, Jonathan

    2009-08-01

    Numerous biological interactions, such as interactions between T cell receptors or antibodies with antigens, interactions between enzymes and substrates, or interactions between predators and prey are often not strictly specific. In such less specific, or "sloppy," systems, referred to here as degenerate systems, a given unit of a diverse resource (antigens, enzymatic substrates, prey) is at risk of being recognized and consumed by multiple consumers (lymphocytes, enzymes, predators). In this study, we model generalized degenerate consumer-resource systems of Lotka-Volterra and Verhulst types. In the degenerate systems of Lotka-Volterra, there is a continuum of types of consumer and resource based on variation of a single trait (characteristic, or preference). The consumers experience competition for a continuum of resource types. This non-local interaction system is modeled with partial differential-integral equations and shows spontaneous self-structuring of the consumer population that depends on the degree of interaction degeneracy between resource and consumer, but does not mirror the distribution of resource. We also show that the classical Verhulst (i.e. logistic) single population model can be generalized to a degenerate model, which shows qualitative behavior similar to that in the degenerate Lotka-Volterra model. These results provide better insight into the dynamics of selective systems in biology, suggesting that adaptation of degenerate repertoires is not a simple "mirroring" of the environment by the "fittest" elements of population.

  9. Accurate and High-Coverage Immune Repertoire Sequencing Reveals Characteristics of Antibody Repertoire Diversification in Young Children with Malaria

    Science.gov (United States)

    Jiang, Ning

    Accurately measuring the immune repertoire sequence composition, diversity, and abundance is important in studying repertoire response in infections, vaccinations, and cancer immunology. Using molecular identifiers (MIDs) to tag mRNA molecules is an effective method in improving the accuracy of immune repertoire sequencing (IR-seq). However, it is still difficult to use IR-seq on small amount of clinical samples to achieve a high coverage of the repertoire diversities. This is especially challenging in studying infections and vaccinations where B cell subpopulations with fewer cells, such as memory B cells or plasmablasts, are often of great interest to study somatic mutation patterns and diversity changes. Here, we describe an approach of IR-seq based on the use of MIDs in combination with a clustering method that can reveal more than 80% of the antibody diversity in a sample and can be applied to as few as 1,000 B cells. We applied this to study the antibody repertoires of young children before and during an acute malaria infection. We discovered unexpectedly high levels of somatic hypermutation (SHM) in infants and revealed characteristics of antibody repertoire development in young children that would have a profound impact on immunization in children.

  10. An Automated Method for Extracting Spatially Varying Time-Dependent Quantities from an ALEGRA Simulation Using VisIt Visualization Software

    Science.gov (United States)

    2014-07-01

    Visualization software such as VisIt presents an alternative method to examine data through the use of EXODUS databases.3 In addition, VisIt...extracting transient quantities that vary spatially from an EXODUS database using a VisIt macro written in the Python programming language. 2...Graphics; Sandia National Laboratories: Albuquerque, NM, September 1991. Revised April 1994. 3 Schoof, L. A.; Yarberry, V. R. EXODUS II: A Finite

  11. The time-dependent coupled oscillator model for the motion of a charged particle in the presence of a time-varying magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Menouar, Salah; Maamache, Mustapha [Laboratoire de Physique Quantique et Systemes Dynamiques, Departement de Physique, Faculte des Sciences, Universite Ferhat Abbas de Setif, Setif 19000 (Algeria); Choi, Jeong Ryeol, E-mail: menouar_salah@yahoo.f, E-mail: choiardor@hanmail.ne [Department of Radiologic Technology, Daegu Health College, Taejeon 1-dong, Buk-gu, Daegu 702-722 (Korea, Republic of)

    2010-12-15

    The dynamics of the time-dependent coupled oscillator model for the motion of a charged particle subjected to a time-dependent external magnetic field is investigated. We use the canonical transformation approach for the classical treatment of the system, whereas the unitary transformation approach is used in managing the system in the framework of quantum mechanics. For both approaches, the original system is transformed into a much more simple system that is the sum of two independent harmonic oscillators with time-dependent frequencies. We therefore easily identify the wavefunctions in the transformed system with the help of an invariant operator of the system. The full wavefunctions in the original system are derived from the inverse unitary transformation of the wavefunctions associated with the transformed system.

  12. Fluorosis varied treatment options

    OpenAIRE

    Sherwood I

    2010-01-01

    Fluorosis has been reported way back in 1901. The treatment options for fluorosis are varied depending upon individual cases. This article comes from Madurai in India where its surrounding towns are fluorosis-prone zones. The purpose of this article is to report various treatment options available for dental fluorosis; this is the first time that complete full mouth rehabilitation for dental fluorosis is being reported. This article also dwells on the need for the dentists to be aware of thei...

  13. Repertoires of spike avalanches are modulated by behavior and novelty

    Directory of Open Access Journals (Sweden)

    Tiago Lins Ribeiro

    2016-03-01

    Full Text Available Neuronal avalanches measured as consecutive bouts of thresholded field potentials represent a statistical signature that the brain operates near a critical point. In theory, criticality optimizes stimulus sensitivity, information transmission, computational capability and mnemonic repertoires size. Field potential avalanches recorded via multielectrode arrays from cortical slice cultures are repeatable spatiotemporal activity patterns. It remains unclear whether avalanches of action potentials observed in forebrain regions of freely-behaving rats also form recursive repertoires, and whether these have any behavioral relevance. Here we show that spike avalanches, recorded from hippocampus and sensory neocortex of freely-behaving rats, constitute distinct families of recursive spatiotemporal patterns. A significant number of those patterns were specific to a behavioral state. Although avalanches produced during sleep were mostly similar to others that occurred during waking, the repertoire of patterns recruited during sleep differed significantly from that of waking. More importantly, exposure to novel objects increased the rate at which new patterns arose, also leading to changes in post-exposure repertoires, which were significantly different from those before the exposure. A significant number of families occurred exclusively during periods of whisker contact with objects, but few were associated with specific objects. Altogether, the results provide original evidence linking behavior and criticality at the spike level: spike avalanches form repertoires that emerge in waking, recur during sleep, are diversified by novelty and contribute to object representation.

  14. Repertoires of Spike Avalanches Are Modulated by Behavior and Novelty.

    Science.gov (United States)

    Ribeiro, Tiago L; Ribeiro, Sidarta; Copelli, Mauro

    2016-01-01

    Neuronal avalanches measured as consecutive bouts of thresholded field potentials represent a statistical signature that the brain operates near a critical point. In theory, criticality optimizes stimulus sensitivity, information transmission, computational capability and mnemonic repertoires size. Field potential avalanches recorded via multielectrode arrays from cortical slice cultures are repeatable spatiotemporal activity patterns. It remains unclear whether avalanches of action potentials observed in forebrain regions of freely-behaving rats also form recursive repertoires, and whether these have any behavioral relevance. Here, we show that spike avalanches, recorded from hippocampus (HP) and sensory neocortex of freely-behaving rats, constitute distinct families of recursive spatiotemporal patterns. A significant number of those patterns were specific to a behavioral state. Although avalanches produced during sleep were mostly similar to others that occurred during waking, the repertoire of patterns recruited during sleep differed significantly from that of waking. More importantly, exposure to novel objects increased the rate at which new patterns arose, also leading to changes in post-exposure repertoires, which were significantly different from those before the exposure. A significant number of families occurred exclusively during periods of whisker contact with objects, but few were associated with specific objects. Altogether, the results provide original evidence linking behavior and criticality at the spike level: spike avalanches form repertoires that emerge in waking, recur during sleep, are diversified by novelty and contribute to object representation.

  15. Human KIR repertoires: shaped by genetic diversity and evolution.

    Science.gov (United States)

    Manser, Angela R; Weinhold, Sandra; Uhrberg, Markus

    2015-09-01

    Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals' immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.

  16. Enhanced repertoire of brain dynamical states during the psychedelic experience.

    Science.gov (United States)

    Tagliazucchi, Enzo; Carhart-Harris, Robin; Leech, Robert; Nutt, David; Chialvo, Dante R

    2014-11-01

    The study of rapid changes in brain dynamics and functional connectivity (FC) is of increasing interest in neuroimaging. Brain states departing from normal waking consciousness are expected to be accompanied by alterations in the aforementioned dynamics. In particular, the psychedelic experience produced by psilocybin (a substance found in "magic mushrooms") is characterized by unconstrained cognition and profound alterations in the perception of time, space and selfhood. Considering the spontaneous and subjective manifestation of these effects, we hypothesize that neural correlates of the psychedelic experience can be found in the dynamics and variability of spontaneous brain activity fluctuations and connectivity, measurable with functional Magnetic Resonance Imaging (fMRI). Fifteen healthy subjects were scanned before, during and after intravenous infusion of psilocybin and an inert placebo. Blood-Oxygen Level Dependent (BOLD) temporal variability was assessed computing the variance and total spectral power, resulting in increased signal variability bilaterally in the hippocampi and anterior cingulate cortex. Changes in BOLD signal spectral behavior (including spectral scaling exponents) affected exclusively higher brain systems such as the default mode, executive control, and dorsal attention networks. A novel framework enabled us to track different connectivity states explored by the brain during rest. This approach revealed a wider repertoire of connectivity states post-psilocybin than during control conditions. Together, the present results provide a comprehensive account of the effects of psilocybin on dynamical behavior in the human brain at a macroscopic level and may have implications for our understanding of the unconstrained, hyper-associative quality of consciousness in the psychedelic state. Copyright © 2014 Wiley Periodicals, Inc.

  17. T-cell repertoires in refractory coeliac disease.

    Science.gov (United States)

    Ritter, Julia; Zimmermann, Karin; Jöhrens, Korinna; Mende, Stefanie; Seegebarth, Anke; Siegmund, Britta; Hennig, Steffen; Todorova, Kremena; Rosenwald, Andreas; Daum, Severin; Hummel, Michael; Schumann, Michael

    2017-02-10

    Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n=8), RCD type II (n=8) and unclassified Marsh I cases (n=3) collected from 2002 to 2013 was examined by TCRβ-complementarity-determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. On average, 10(6) sequence reads per sample were generated consisting of up to 900 individual TCRβ rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6% of all TCRβ rearrangements, which was significantly higher than in controls (6.8%; pRCD type I (6.7%; pRCD type II were unique and not related between patients. CD-associated, gliadin-dependent CDR3 motifs were only detectable at low frequencies. TCRβ-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCRβ rearrangements. Dominant TCRβ sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. The repertoire of bitter taste receptor genes in canids.

    Science.gov (United States)

    Shang, Shuai; Wu, Xiaoyang; Chen, Jun; Zhang, Huanxin; Zhong, Huaming; Wei, Qinguo; Yan, Jiakuo; Li, Haotian; Liu, Guangshuai; Sha, Weilai; Zhang, Honghai

    2017-07-01

    Bitter taste receptors (Tas2rs) play important roles in mammalian defense mechanisms by helping animals detect and avoid toxins in food. Although Tas2r genes have been widely studied in several mammals, minimal research has been performed in canids. To analyze the genetic basis of Tas2r genes in canids, we first identified Tas2r genes in the wolf, maned wolf, red fox, corsac fox, Tibetan fox, fennec fox, dhole and African hunting dog. A total of 183 Tas2r genes, consisting of 118 intact genes, 6 partial genes and 59 pseudogenes, were detected. Differences in the pseudogenes were observed among nine canid species. For example, Tas2r4 was a pseudogene in the dog but might play a functional role in other canid species. The Tas2r42 and Tas2r10 genes were pseudogenes in the maned wolf and dhole, respectively, and the Tas2r5 and Tas2r34 genes were pseudogenes in the African hunting dog; however, these genes were intact genes in other canid species. The differences in Tas2r pseudogenes among canids might suggest that the loss of intact Tas2r genes in canid species is species-dependent. We further compared the 183 Tas2r genes identified in this study with Tas2r genes from ten additional carnivorous species to evaluate the potential influence of diet on the evolution of the Tas2r gene repertoire. Phylogenetic analysis revealed that most of the Tas2r genes from the 18 species intermingled across the tree, suggesting that Tas2r genes are conserved among carnivores. Within canids, we found that some Tas2r genes corresponded to the traditional taxonomic groupings, while some did not. PIC analysis showed that the number of Tas2r genes in carnivores exhibited no positive correlation with diet composition, which might be due to the limited number of carnivores included in our study.

  19. Time-Independent and Time-Dependent Rheological Characterization of Dispersions with Varying Contents of Chickpea Flour and Gum Arabic Employing the Multiple Loop Experiments.

    Science.gov (United States)

    J, Shanthilal; Bhattacharya, Suvendu

    2016-08-01

    The chickpea (Cicer arietinum) flour dispersions as the model system with different contents of flour (37% to 43%) and gum arabic (0% to 5%) were subjected to multiple loop experiments for simultaneous determination of the time-independent and time-dependent rheological characteristics. The Herschel-Bulkley model was suitable (0.993 ≤ r ≤ 0.999) to relate the time-independent characteristics linking shear stress and shear rate data for the individual upward and downward curves. The yield stress, consistency index, and apparent viscosity increased with the increasing flour and/or gum contents while flow behavior index (n) decreased. The yield stress generally decreased with the number of loops but n increased. In the individual loop tests, the n values for the decreasing shear stress/shear rate curves were always higher than corresponding increasing curves meaning a shift toward Newtonian characteristics. The time-independent properties (yield stress, apparent viscosity, consistency index, and n), the time-dependent characteristics like the area of the loop, and liquid characteristics like pourability and the nonoral sensory attributes (viscosity, spreadability, and tackiness) were individually predicted by artificial neural networks wherein the root mean square errors were between 3.6% and 17.2%. The sensory assessment indicated that the desirable parameters for a free-flowing and easily pourable spherical chickpea batter droplets occurred when the average pourability and spreadability values were 6.9 and 5.9, respectively. The normalized indices for these 2 parameters indicated that the batter having 40% flour and 2% gum contents was most suitable exhibiting a deviation of only 10% from the ideal sensory scores; these values were 40% and 0% to 3%, and 43% and 0%, respectively exhibiting up to 20% deviation.

  20. Protest Leadership and Repertoire: A Comparative Analysis of Peasant Protest in Hunan in the 1990s

    Directory of Open Access Journals (Sweden)

    Wu Zhang

    2013-01-01

    Full Text Available Based on detailed ethnographic fieldwork, this paper compares two cases of peasant protest against heavy taxes and fees in a northern Hunan county in the 1990s. It argues that peasant protest did not arise spontaneously. Rather, it erupted when leaders emerged who used central policy documents on lowering peasant taxes and fees to mobilise peasants. Protest leaders were articulate and public-spirited peasants who had received political training from the local party-state. Furthermore, the number of leaders, their education level, and their relationship with the local party-state explain why the repertoire and the scope of the two protests varied. Protests led by less educated veteran Communist Party cadres tended to be milder and smaller than those led by better-educated peasants more distant from the local party-state. This paper helps us to understand the process of peasant mobilisation in contemporary China and explains why peasant protest varies across cases.

  1. [Independence in Plastic Surgery - Benefit or Barrier? Analysis of the Publication Performance in Academic Plastic Surgery Depending on Varying Organisational Structures].

    Science.gov (United States)

    Schubert, C D; Leitsch, S; Haertnagl, F; Haas, E M; Giunta, R E

    2015-08-01

    Despite its recognition as an independent specialty, at German university hospitals the field of plastic surgery is still underrepresented in terms of independent departments with a dedicated research focus. The aim of this study was to analyse the publication performance within the German academic plastic surgery environment and to compare independent departments and dependent, subordinate organisational structures regarding their publication performance. Organisational structures and number of attending doctors in German university hospitals were examined via a website analysis. A pubmed analysis was applied to assess the publication performance (number of publications, cumulative impact factor, impact factor/publication, number of publications/MD, number of publications/unit) between 2009 and 2013. In a journal analysis the distribution of the cumulative impact factor and number of publications in different journals as well as the development of the impact factor in the top journals were analysed. Out of all 35 university hospitals there exist 12 independent departments for plastic surgery and 8 subordinate organisational structures. In 15 university hospitals there were no designated plastic surgery units. The number of attending doctors differed considerably between independent departments (3.6 attending doctors/unit) and subordinate organisational structures (1.1 attending doctors/unit). The majority of publications (89.0%) and of the cumulative impact factor (91.2%) as well as most of the publications/MD (54 publications/year) and publications/unit (61 publications/year) were created within the independent departments. Only in departments top publications with an impact factor > 5 were published. In general a negative trend regarding the number of publications (- 13.4%) and cumulative impact factor (- 28.9%) was observed. 58.4% of all publications were distributed over the top 10 journals. Within the latter the majority of articles were published in

  2. Height-dependent sunrise and sunset: Effects and implications of the varying times of occurrence for local ionospheric processes and modelling

    Science.gov (United States)

    Verhulst, Tobias G. W.; Stankov, Stanimir M.

    2017-10-01

    It is well established that the sunrise and sunset periods are of particular importance to ionospheric research and modelling because of the rapid changes in the ionospheric plasma density, temperature, and dynamics. In particular, the sharp increase in the ionisation following sunrise results in a quick increase in the ionospheric peak density, NmF2 , and a decrease in the peak height, hmF2 . Changes in plasma temperature, scale height and transport processes add further complexity which makes it difficult to investigate and model the ionospheric behaviour during this transitional period from night to day. One of the aspects contributing to this difficulty is that not all ionospheric altitudes are exposed to the first sunlight of the day at the same time. During sunrise, the upper part of the ionosphere is illuminated prior to the lower part which is still in the dark. The boundary between sunlit and dark regions moves downwards until it reaches the surface of the Earth, which is commonly taken as the moment of sunrise at certain geographical coordinates. This means that the sunrise at surface level does not occur until after the entire ionosphere has been illuminated. During sunset, the same process happens in reverse order. This paper addresses the issue of these altitude-dependent times of sunrise and sunset and reports on our study of some of the effects on the diurnal variations in the ionospheric characteristics.

  3. Surveillance and Management Repertoires in Distributed Forms of Organisations

    DEFF Research Database (Denmark)

    Buser, Martine; Koch, Christian

    on the relations between changes in management and surveillance. Management is here understood as a repertoire of activities including coordination, assignment of tasks, coaching, control surveillance and others, drawing on the genre concept used by Orlikowsky & Yates (1994). It is understood that these attributes...

  4. Perspectives on Linguistic Repertoires in Adult Multilinguals: An Epilogue

    Science.gov (United States)

    Gorter, Durk

    2017-01-01

    This article introduces this special issue by declaring that the studies contained here build on the idea that multilinguals, in the sense of learners or speakers that have more than two languages in their linguistic repertoire, are different from bilinguals and monolinguals in various ways. Several authors in the area of third language…

  5. Fluorosis varied treatment options

    Directory of Open Access Journals (Sweden)

    Sherwood I

    2010-01-01

    Full Text Available Fluorosis has been reported way back in 1901. The treatment options for fluorosis are varied depending upon individual cases. This article comes from Madurai in India where its surrounding towns are fluorosis-prone zones. The purpose of this article is to report various treatment options available for dental fluorosis; this is the first time that complete full mouth rehabilitation for dental fluorosis is being reported. This article also dwells on the need for the dentists to be aware of their local indigenous pathologies to treat it in a better manner.

  6. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or posttranscriptional processing of coding genes

    Directory of Open Access Journals (Sweden)

    Atanu eGhorai

    2014-04-01

    Full Text Available MicroRNAs target specific mRNA(s to silence its expression and thereby regulate various cellular processes. We have investigated miRNA gene counts in chromosomes for 20 different species and observed wide variation. Certain chromosomes have extremely high number of miRNA gene compared with others in all the species. For example, high number of miRNA gene in X chromosome and the least or absence of miRNA gene in Y chromosome was observed in all species. To search the criteria governing such variation of miRNA gene counts in chromosomes, we have selected three parameters- length, number of non-coding and coding genes in a chromosome. We have calculated Pearson’s correlation coefficient of miRNA gene counts with length, number of non-coding and coding genes in a chromosome for all 20 species. Major number of species showed that number of miRNA gene was not correlated with chromosome length. 85% of species under study showed strong positive correlation coefficient (r≥0.5 between the numbers of miRNA gene vs non-coding gene in chromosomes as expected because miRNA is a sub-set of non-coding genes. 55% species under study showed strong positive correlation coefficient (r≥0.5 between numbers of miRNA gene vs coding gene. We hypothesize biogenesis of miRNA largely depends on coding genes, an evolutionary conserved process. Chromosomes having higher number of miRNA genes will be most likely playing regulatory roles in several cellular processes including different disorders. In humans, cancer and cardiovascular disease associated miRNAs are mostly intergenic and located in Chromosome 19, X, 14 and 1.

  7. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells.

    Science.gov (United States)

    Buchanan, Grant; Need, Eleanor F; Barrett, Jeffrey M; Bianco-Miotto, Tina; Thompson, Vanessa C; Butler, Lisa M; Marshall, Villis R; Tilley, Wayne D; Coetzee, Gerhard A

    2011-08-01

    The response of prostate cells to androgens reflects a combination of androgen receptor (AR) transactivation and transrepression, but how these two processes differ mechanistically and influence prostate cancer risk and disease outcome remain elusive. Given recent interest in targeting AR transrepressive processes, a better understanding of AR/corepressor interaction and responses is warranted. Here, we used transactivation and interaction assays with wild-type and mutant ARs, and deletion AR fragments, to dissect the relationship between AR and the corepressor, silencing mediator for retinoic acid and thyroid hormone receptors (SMRT). We additionally tested how these processes are influenced by AR agonist and antagonist ligands, as well as by variation in the polyglutamine tract in the AR amino terminal domain (NTD), which is encoded by a polymorphic CAG repeat in the gene. SMRT was recruited to the AR ligand binding domain by agonist ligand, and as determined by the effect of strategic mutations in activation function 2 (AF-2), requires a precise conformation of that domain. A distinct region of SMRT also mediated interaction with the AR-NTD via the transactivation unit 5 (TAU5; residues 315-538) region. The degree to which SMRT was able to repress AR increased from 17% to 56% as the AR polyglutamine repeat length was increased from 9 to 42 residues, but critically this effect could be abolished by increasing the SMRT:AR molar ratio. These data suggest that the extent to which the CAG encoded polyglutamine repeat influences AR activity represents a balance between corepressor and coactivator occupancy of the same ligand-dependent and independent AR interaction surfaces. Changes in the homeostatic relationship of AR to these molecules, including SMRT, may explain the variable penetrance of the CAG repeat and the loss of AR signaling flexibility in prostate cancer progression.

  8. Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

    Directory of Open Access Journals (Sweden)

    Phillips Ruth B

    2010-10-01

    Full Text Available Abstract Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon

  9. The past, present and future of immune repertoire biology – the rise of next-generation repertoire analysis

    Directory of Open Access Journals (Sweden)

    Adrien eSix

    2013-11-01

    Full Text Available T and B cell repertoires are collections of lymphocytes, each characterised by its antigen-specific receptor. We review here classical technologies and analysis strategies developed to assess Immunoglobulin (IG and T cell receptor (TR repertoire diversity, and describe recent advances in the field. First, we describe the broad range of available methodological tools developed in the past decades, each of which answering different questions and showing complementarity for progressive identification of the level of repertoire alterations: global overview of the diversity by flow cytometry, IG repertoire descriptions at the protein level for the identification of IG reactivities, IG/TR CDR3 spectratyping strategies, and related molecular quantification or dynamics of T/B cell differentiation. Additionally, we introduce the recent technological advances in molecular biology tools allowing deeper analysis of IG/TR diversity by next-generation sequencing (NGS, offering systematic and comprehensive sequencing of IG/TR transcripts in a short amount of time. NGS provides several angles of analysis such as clonotype frequency, CDR3 diversity, CDR3 sequence analysis, V allele identification with a quantitative dimension, therefore requiring high-throughput analysis tools development. In this line, we discuss the recent efforts made for nomenclature standardisation and ontology development. We then present the variety of available statistical analysis and modelling approaches developed with regards to the various levels of diversity analysis, and reveal the increasing sophistication of modelling approaches. To conclude, we provide some examples of recent mathematical modelling strategies and perspectives that illustrate the active rise of a next-generation of repertoire analysis.

  10. 股指期货对现货时变相依结构的多尺度研究%Multi-scale Study on Time-varying Dependency Structure between the Stock Index Futures and the Actual

    Institute of Scientific and Technical Information of China (English)

    彭选华; 傅强

    2011-01-01

    Copula theory is very popular to model the dependency structure between the price of future and spot market in financial analysis including risk hedge,hedging portfolio and price discovery.This paper considers the innovation asymmetric impact on the price and the time-varying characteristics of the dependency structure,and constructs a time-varying T-Copula-GJR-GARCH model by using a GJR-GARCH model to fit the two returns,respectively.By choosing the DCC equation to depict the dynamic structure of the time-varying coefficient,and based on high frequency price data from 5 to 60 minute of the Hu-Shen 300 index futures and stock market,we establish a time-varying T-Copula-GJR-GARCH(1,1)-T model by time-scale.The results indicate the dependent structure changes over time-scale,which may be explained by the market microstructure and heterogeneity of the investors.Hence,this paper reveals the potential time-varying dependency patterns between China's stock index futures and spot market at multi-scale time horizons.%股指期货与现货之间的相依结构是Copula理论在金融分析中套期保值、组合风险对冲及价格发现等应用的热点。考虑到新息对价格的非对称冲击和相依结构的时变特征,利用GJR-GARCH模型对股指期货和现货的收益率序列建模,选用DCC方程刻画二者之间时变相关系数的演化结构,构建时变T-Copula-GJR-GARCH模型。针对沪深300指数现货与期货5~60分钟的高频数据,分尺度拟合时变T-Copula-GJR-GARCH(1,1)-t模型,结果表明相依结构随时间尺度变化而变化,这或许可由市场微观结构差异及投资者的

  11. Antibody repertoire development in fetal and neonatal piglets XXI. Usage of most VH genes remains constant during fetal and postnatal development.

    Science.gov (United States)

    Butler, John E; Sun, Xuizhu; Wertz, Nancy; Lager, Kelly M; Chaloner, Kathryn; Urban, Joseph; Francis, David L; Nara, Peter L; Tobin, Gregory J

    2011-12-01

    Usage of variable region gene segments during development of the antibody repertoire in mammals is unresolved in part because of the complexity of the locus in mice and humans and the difficulty of distinguishing intrinsic from extrinsic influences in these species. We present the first vertical studies on VH usage that spans the fetal and neonatal period using the piglet model. We tracked VH usage in DNA rearrangements and in VDJ transcripts throughout 75 days of gestation (DG) in outbred fetuses, thereafter in outbred germfree and colonized isolator piglets, isolator piglets infected with swine influenza and in conventionally reared nematode-infected adults. Seven VH genes account for >90% of the pre-immune repertoire which is the same among tissues and in both transcripts and DNA rearrangements. Statistical modeling supports the view that proportional usage of the major genes remains constant during fetal life and that postnatal usage ranking is similar to that during fetal life. Changes in usage ranking are developmental not antigen dependent. In this species exposure to environmental antigens results in diversification of the repertoire by somatic hypermutation of the same small number of VH genes that comprise the pre-immune repertoire, not by using other VH gene available in the germline. Therefore in swine a small number of VH genes shape the antibody repertoire throughout life questioning the need for extensive VH polygeny.

  12. Linking experiences with emotions and the development of interpretive repertoires

    Science.gov (United States)

    McRae, Norah I.

    2010-03-01

    In this paper I consider the case of one student, Todd Alexander, through analyzing the transcripts of his interviews between him and his teacher (Wolff-Michael Roth). I examine the role that emotions play in the development of the interpretive repertoires that Todd employed as he talked about his scientific and his religious beliefs. I identify how lived experiences support the development of emotions and what educational conditions are necessary to allow for appropriate lived experiences. In so doing we might be able to support educational conditions that result in interpretive repertoires that allow for acceptance of multiple perspectives with a moral grounding, leading to students who are well positioned to be valuable contributors to society.

  13. Variation in the Genetic Repertoire of Viruses Infecting Micromonas pusilla Reflects Horizontal Gene Transfer and Links to Their Environmental Distribution

    Science.gov (United States)

    Finke, Jan F.; Winget, Danielle M.; Chan, Amy M.; Suttle, Curtis A.

    2017-01-01

    Prasinophytes, a group of eukaryotic phytoplankton, has a global distribution and is infected by large double-stranded DNA viruses (prasinoviruses) in the family Phycodnaviridae. This study examines the genetic repertoire, phylogeny, and environmental distribution of phycodnaviruses infecting Micromonas pusilla, other prasinophytes and chlorophytes. Based on comparisons among the genomes of viruses infecting M. pusilla and other phycodnaviruses, as well as the genome from a host isolate of M. pusilla, viruses infecting M. pusilla (MpVs) share a limited set of core genes, but vary strongly in their flexible pan-genome that includes numerous metabolic genes, such as those associated with amino acid synthesis and sugar manipulation. Surprisingly, few of these presumably host-derived genes are shared with M. pusilla, but rather have their closest non-viral homologue in bacteria and other eukaryotes, indicating horizontal gene transfer. A comparative analysis of full-length DNA polymerase (DNApol) genes from prasinoviruses with their overall gene content, demonstrated that the phylogeny of DNApol gene fragments reflects the gene content of the viruses; hence, environmental DNApol gene sequences from prasinoviruses can be used to infer their overall genetic repertoire. Thus, the distribution of virus ecotypes across environmental samples based on DNApol sequences implies substantial underlying differences in gene content that reflect local environmental conditions. Moreover, the high diversity observed in the genetic repertoire of prasinoviruses has been driven by horizontal gene transfer throughout their evolutionary history, resulting in a broad suite of functional capabilities and a high diversity of prasinovirus ecotypes. PMID:28534829

  14. Antibody repertoire development in cartilaginous fish.

    Science.gov (United States)

    Dooley, H; Flajnik, M F

    2006-01-01

    There are 3 H chain and 3 L chain isotypes in the cartilaginous fish, all encoded by genes in the so-called cluster (VDDJ, VJ) organization. The H chain isotypes IgM and IgNAR, are readily detected at the protein level in most species. The third is readily identified at the protein level in skates (IgR) but only via immunoprecipitation or at the transcript level in sharks (IgW). High levels of diversity in CDR3 and up to 200 germline genes have been detected for IgM depending upon the species examined. IgNAR displays very high levels of CDR3 diversity but almost none in the germline. At least IgNAR and L chain genes have been shown to hypermutate to very high levels, apparently in response to antigen. The mutation footprints are similar to those in mammals except that the shark genes uniquely mutate nucleotide residues in tandem. A conspicuous feature of cartilaginous fish Ig genes is the presence of germline-joined genes, which are a result of RAG activity in germ cells. Such genes are expressed early in ontogeny and then extinguished or expressed at lower levels. 19S IgM and IgW expression precede that of 7S IgM and IgNAR during ontogeny. The 'switch' from 19S to 7S IgM, the regulation of expression of the Ig clusters, and the microenvironments for mutation/selection of cartilaginous fish B cells are all areas of ongoing research.

  15. Mother and child T cell receptor repertoires: deep profiling study

    Directory of Open Access Journals (Sweden)

    Ekaterina V Putintseva

    2013-12-01

    Full Text Available The relationship between maternal and child immunity has been actively studied in the context of complications during pregnancy, autoimmune diseases, and haploidentical transplantation of hematopoietic stem cells (HSC and solid organs. Here, we have for the first time used high-throughput Illumina HiSeq sequencing to perform deep quantitative profiling of T-cell receptor (TCR repertoires for peripheral blood samples of three mothers and their six children. Advanced technology allowed accurate identification of 5х105–2х106 TCR beta clonotypes per individual. We performed comparative analysis of these TCR repertoires with the aim of revealing characteristic features that distinguish related mother-child pairs, such as relative TRBV segment usage frequency and relative overlap of TCR beta CDR3 repertoires. We show that thymic selection essentially and similarly shapes the initial output of the TCR recombination machinery in both related and unrelated pairs, with minor effect from inherited differences. The achieved depth of TCR profiling also allowed us to test the hypothesis that mature T cells transferred across the placenta during pregnancy can expand and persist as functional microchimeric clones in their new host, using characteristic TCR beta CDR3 variants as clonal identifiers.

  16. Serum Antibody Repertoire Profiling Using In Silico Antigen Screen.

    Directory of Open Access Journals (Sweden)

    Xinyue Liu

    Full Text Available Serum antibodies are valuable source of information on the health state of an organism. The profiles of serum antibody reactivity can be generated by using a high throughput sequencing of peptide-coding DNA from combinatorial random peptide phage display libraries selected for binding to serum antibodies. Here we demonstrate that the targets of immune response, which are recognized by serum antibodies directed against sequential epitopes, can be identified using the serum antibody repertoire profiles generated by high throughput sequencing. We developed an algorithm to filter the results of the protein database BLAST search for selected peptides to distinguish real antigens recognized by serum antibodies from irrelevant proteins retrieved randomly. When we used this algorithm to analyze serum antibodies from mice immunized with human protein, we were able to identify the protein used for immunizations among the top candidate antigens. When we analyzed human serum sample from the metastatic melanoma patient, the recombinant protein, corresponding to the top candidate from the list generated using the algorithm, was recognized by antibodies from metastatic melanoma serum on the western blot, thus confirming that the method can identify autoantigens recognized by serum antibodies. We demonstrated also that our unbiased method of looking at the repertoire of serum antibodies reveals quantitative information on the epitope composition of the targets of immune response. A method for deciphering information contained in the serum antibody repertoire profiles may help to identify autoantibodies that can be used for diagnosing and monitoring autoimmune diseases or malignancies.

  17. Determinism and stochasticity during maturation of the zebrafish antibody repertoire

    Science.gov (United States)

    Jiang, Ning; Weinstein, Joshua A.; Penland, Lolita; White, Richard A.; Fisher, Daniel S.; Quake, Stephen R.

    2011-01-01

    It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity. PMID:21393572

  18. Unifying model for molecular determinants of the preselection Vβ repertoire.

    Science.gov (United States)

    Gopalakrishnan, Suhasni; Majumder, Kinjal; Predeus, Alexander; Huang, Yue; Koues, Olivia I; Verma-Gaur, Jiyoti; Loguercio, Salvatore; Su, Andrew I; Feeney, Ann J; Artyomov, Maxim N; Oltz, Eugene M

    2013-08-20

    The primary antigen receptor repertoire is sculpted by the process of V(D)J recombination, which must strike a balance between diversification and favoring gene segments with specialized functions. The precise determinants of how often gene segments are chosen to complete variable region coding exons remain elusive. We quantified Vβ use in the preselection Tcrb repertoire and report relative contributions of 13 distinct features that may shape their recombination efficiencies, including transcription, chromatin environment, spatial proximity to their DβJβ targets, and predicted quality of recombination signal sequences (RSSs). We show that, in contrast to functional Vβ gene segments, all pseudo-Vβ segments are sequestered in transcriptionally silent chromatin, which effectively suppresses wasteful recombination. Importantly, computational analyses provide a unifying model, revealing a minimum set of five parameters that are predictive of Vβ use, dominated by chromatin modifications associated with transcription, but largely independent of precise spatial proximity to DβJβ clusters. This learned model-building strategy may be useful in predicting the relative contributions of epigenetic, spatial, and RSS features in shaping preselection V repertoires at other antigen receptor loci. Ultimately, such models may also predict how designed or naturally occurring alterations of these loci perturb the preselection use of variable gene segments.

  19. Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Hanna eIJspeert

    2015-04-01

    Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

  20. Strategies for B-Cell Receptor Repertoire Analysis in Primary Immunodeficiencies: From Severe Combined Immunodeficiency to Common Variable Immunodeficiency

    Science.gov (United States)

    IJspeert, Hanna; Wentink, Marjolein; van Zessen, David; Driessen, Gertjan J.; Dalm, Virgil A. S. H.; van Hagen, Martin P.; Pico-Knijnenburg, Ingrid; Simons, Erik J.; van Dongen, Jacques J. M.; Stubbs, Andrew P.; van der Burg, Mirjam

    2015-01-01

    The antigen receptor repertoires of B- and T-cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective, we describe strategies and considerations for analysis of the naive and antigen-selected B-cell repertoires in primary immunodeficiency patients with a focus on severe combined immunodeficiency and common variable immunodeficiency. PMID:25904919

  1. Characterizing Vocal Repertoires--Hard vs. Soft Classification Approaches.

    Directory of Open Access Journals (Sweden)

    Philip Wadewitz

    Full Text Available To understand the proximate and ultimate causes that shape acoustic communication in animals, objective characterizations of the vocal repertoire of a given species are critical, as they provide the foundation for comparative analyses among individuals, populations and taxa. Progress in this field has been hampered by a lack of standard in methodology, however. One problem is that researchers may settle on different variables to characterize the calls, which may impact on the classification of calls. More important, there is no agreement how to best characterize the overall structure of the repertoire in terms of the amount of gradation within and between call types. Here, we address these challenges by examining 912 calls recorded from wild chacma baboons (Papio ursinus. We extracted 118 acoustic variables from spectrograms, from which we constructed different sets of acoustic features, containing 9, 38, and 118 variables; as well 19 factors derived from principal component analysis. We compared and validated the resulting classifications of k-means and hierarchical clustering. Datasets with a higher number of acoustic features lead to better clustering results than datasets with only a few features. The use of factors in the cluster analysis resulted in an extremely poor resolution of emerging call types. Another important finding is that none of the applied clustering methods gave strong support to a specific cluster solution. Instead, the cluster analysis revealed that within distinct call types, subtypes may exist. Because hard clustering methods are not well suited to capture such gradation within call types, we applied a fuzzy clustering algorithm. We found that this algorithm provides a detailed and quantitative description of the gradation within and between chacma baboon call types. In conclusion, we suggest that fuzzy clustering should be used in future studies to analyze the graded structure of vocal repertoires. Moreover, the use of

  2. Enrichment of an in vivo phage display repertoire by subtraction for easy identification of pathology biomarkers

    Directory of Open Access Journals (Sweden)

    karina Vargas Sanchez

    2015-03-01

    Conclusion. This physical subtraction discarded from a complex repertoire the non-specific selected ligands. STRATEGY 1 Three rounds of in vivo phage peptide selection in EAE female Lewis rats ("EAE repertoire" vs controls ("HEALTHY repertoire". 2 DNA subtraction of the most common sequences between «HEALTHY» and «EAE» phage repertoires to obtain a third EAE specific «SUBTRACTION » phage repertoire. 3 Massive sequencing of the three repertoires and bioinformatic analysis to identify the peptides sequences with high EAE specificity. 4 Biological tests of potential EAE specific phage clones with CNS tissues from EAE and Healthy control rats. 5 Biological tests of the EAE specific peptide and phage clones on the BBB in vitro model (hCMEC/D3 cells under inflammatory conditions (IL-1β stimulation. 6 Target separation and identification by cross-link between the selected phage clones and hMEC/D3 endothelial cells targets under IL-1β stimulation vs controls.

  3. From everyday communicative figurations to rigorous audience news repertoires

    DEFF Research Database (Denmark)

    Kobbernagel, Christian; Schrøder, Kim Christian

    2016-01-01

    In the last couple of decades there has been an unprecedented explosion of news media platforms and formats, as a succession of digital and social media have joined the ranks of legacy media. We live in a ‘hybrid media system’ (Chadwick, 2013), in which people build their cross-media news reperto...... of six audience news repertoires in Denmark, also preserves the qualitative thickness of the participants’ verbal accounts of the communicative figurations of their day-in-the-life with the news media...

  4. Limitations in plasticity of the T-cell receptor repertoire.

    OpenAIRE

    Nanda, N K; Apple, R; Sercarz, E.

    1991-01-01

    How constrained is T-cell recognition? Is a truncated T-cell receptor (TCR) repertoire, missing half of its V beta components (where V indicates variable), still broad enough to produce an antigen-specific T-cell response to all determinants? These questions can be answered for certain T-cell antigenic determinants whose response in the wild type is limited to specific gene segments. Our results show that mice with such a deletion in their TCR V beta genes (V beta truncated haplotype, Va beta...

  5. A REPERTOIRE OF INSTRUMENTS EMPLOYED IN PSYCHOLOGICAL COUNSELING

    Directory of Open Access Journals (Sweden)

    Dorina Maria PASCA

    2014-10-01

    Full Text Available According to Carl Rogers and Albert Ellis [1] [2], a new approach to psychological counseling is needed. Consequently, new and practical means to solve problems that ensue as part of the counseling process are required. From this point of view, this article aims at offering a range of alternatives to approach and involve the client (student in order to achieve the envisaged results of counseling. As such, it offers a concise repertoire of instruments that can be employed in psychological counseling.

  6. Units of analysis and kinetic structure of behavioral repertoires.

    Science.gov (United States)

    Thompson, T; Lubinski, D

    1986-09-01

    It is suggested that molar streams of behavior are constructed of various arrangements of three elementary constituents (elicited, evoked, and emitted response classes). An eight-cell taxonomy is elaborated as a framework for analyzing and synthesizing complex behavioral repertoires based on these functional units. It is proposed that the local force binding functional units into a smoothly articulated kinetic sequence arises from temporally arranged relative response probability relationships. Behavioral integration is thought to reflect the joint influence of the organism's hierarchy of relative response probabilities, fluctuating biological states, and the arrangement of environmental and behavioral events in time.

  7. Delay-range-dependent stability for systems with time-varying delays%一类区间时变时滞系统的稳定性分析

    Institute of Scientific and Technical Information of China (English)

    但松健

    2012-01-01

    针对一类区间时变时滞系统的稳定性问题,进行了全局渐近稳定性分析.通过引入时滞分段方法和构建恰当的Lyapunov-Krasovskii泛函,得到了新的区间时滞相关稳定性判定准则.该准则以线性矩阵不等式形式给出,便于利用LMI工具箱对系统的稳定性进行判定.新准则具有较少的保守性,并且在一定范围内保守性随着时滞分段增多而减少,即时滞分段越多,保守性越少.数值仿真算结果例表明了新准则所具有的有效性和较少的保守性.%Aimed at the problem of the stability of systems with time-varying delay in a range, the global asymptotic stability a-nalysis of delay-range-dependent systems with time-varying delays is investigated. A new criterion of the delay-range-dependent stability is derived by introducing an appropriate type of Lyapunov-Krasovskii functional with the idea of delay fractioning and is formulated in terms of a linear matrix inequality (LMI), which can be readily solved via LMI Toolbox. This new criterion based on a delay fractioning approach proves to be much less conservative and the conservatism could be notably reduced by thinning the delay fractioning within a certain range. Finally, a numerical example is given to demonstrate the effectiveness and the less conservative of the proposed criterion.

  8. Time-varying Crash Risk

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Feunoua, Bruno; Jeon, Yoontae

    We estimate a continuous-time model with stochastic volatility and dynamic crash probability for the S&P 500 index and find that market illiquidity dominates other factors in explaining the stock market crash risk. While the crash probability is time-varying, its dynamic depends only weakly on re...

  9. Time-varying Crash Risk

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Feunoua, Bruno; Jeon, Yoontae

    We estimate a continuous-time model with stochastic volatility and dynamic crash probability for the S&P 500 index and find that market illiquidity dominates other factors in explaining the stock market crash risk. While the crash probability is time-varying, its dynamic depends only weakly...... on return variance once we include market illiquidity as an economic variable in the model....

  10. Computational Model Reveals Limited Correlation between Germinal Center B-Cell Subclone Abundancy and Affinity: Implications for Repertoire Sequencing

    Science.gov (United States)

    Reshetova, Polina; van Schaik, Barbera D. C.; Klarenbeek, Paul L.; Doorenspleet, Marieke E.; Esveldt, Rebecca E. E.; Tak, Paul-Peter; Guikema, Jeroen E. J.; de Vries, Niek; van Kampen, Antoine H. C.

    2017-01-01

    Immunoglobulin repertoire sequencing has successfully been applied to identify expanded antigen-activated B-cell clones that play a role in the pathogenesis of immune disorders. One challenge is the selection of the Ag-specific B cells from the measured repertoire for downstream analyses. A general feature of an immune response is the expansion of specific clones resulting in a set of subclones with common ancestry varying in abundance and in the number of acquired somatic mutations. The expanded subclones are expected to have BCR affinities for the Ag higher than the affinities of the naive B cells in the background population. For these reasons, several groups successfully proceeded or suggested selecting highly abundant subclones from the repertoire to obtain the Ag-specific B cells. Given the nature of affinity maturation one would expect that abundant subclones are of high affinity but since repertoire sequencing only provides information about abundancies, this can only be verified with additional experiments, which are very labor intensive. Moreover, this would also require knowledge of the Ag, which is often not available for clinical samples. Consequently, in general we do not know if the selected highly abundant subclone(s) are also the high(est) affinity subclones. Such knowledge would likely improve the selection of relevant subclones for further characterization and Ag screening. Therefore, to gain insight in the relation between subclone abundancy and affinity, we developed a computational model that simulates affinity maturation in a single GC while tracking individual subclones in terms of abundancy and affinity. We show that the model correctly captures the overall GC dynamics, and that the amount of expansion is qualitatively comparable to expansion observed from B cells isolated from human lymph nodes. Analysis of the fraction of high- and low-affinity subclones among the unexpanded and expanded subclones reveals a limited correlation between

  11. Can rarefaction be used to estimate song repertoire size in birds?

    Directory of Open Access Journals (Sweden)

    Kathleen R. PESHEK, Daniel T. BLUMSTEIN

    2011-06-01

    Full Text Available Song repertoire size is the number of distinct syllables, phrases, or song types produced by an individual or population. Repertoire size estimation is particularly difficult for species that produce highly variable songs and those that produce many song types. Estimating repertoire size is important for ecological and evolutionary studies of speciation, studies of sexual selection, as well as studies of how species may adapt their songs to various acoustic environments. There are several methods to estimate repertoire size, however prior studies discovered that all but a full numerical count of song types might have substantial inaccuracies associated with them. We evaluated a somewhat novel approach to estimate repertoire size—rarefaction; a technique ecologists use to measure species diversity on individual and population levels. Using the syllables within American robins’ Turdus migratorius repertoire, we compared the most commonly used techniques of estimating repertoires to the results of a rarefaction analysis. American robins have elaborate and unique songs with few syllables shared between individuals, and there is no evidence that robins mimic their neighbors. Thus, they are an ideal system in which to compare techniques. We found that the rarefaction technique results resembled that of the numerical count, and were better than two alternative methods (behavioral accumulation curves, and capture-recapture to estimate syllable repertoire size. Future estimates of repertoire size, particularly in vocally complex species, may benefit from using rarefaction techniques when numerical counts are unable to be performed [Current Zoology 57 (3: 300–306, 2011].

  12. Element repertoire: change and development with age in Whitethroat Sylvia communis song

    DEFF Research Database (Denmark)

    Balsby, T.J.S.; Hansen, P.

    2010-01-01

    individual male Whitethroats Sylvia communis sampled as 1- and 2-year olds. These males increased the size of their element repertoire between their first and second year, but song length and number of different elements per song did not change. On average, 44.3% of the song elements in the first...... based on the first-year repertoire, which may explain why large song repertoires are mainly expressed by males at least 2 years of age. It would appear, therefore, that song element repertoire size could be a reliable signal of male age....

  13. Kaarel Irdi repertuaaripoliitilised vaated Vanemuise teatri juhina. Kaarel Ird’s Repertoire Policy as Manager of the Vanemuine Theatre

    Directory of Open Access Journals (Sweden)

    Jaak Viller

    2012-04-01

    to be treated as Soviet plays, and that these works should count towards the quota of Soviet plays. The disproportion between the large amount of attention given to original works and the varying literary level and quality of the contemporary Estonian plays gave rise to sharp public polemics in the first half of the 1960s, which also affected the actors at the theatre. Ird took these viewpoints into consideration, and directed more attention to the quality of the plays. The same kind of a turning point also took place in relation to the contemporary Russian and Soviet drama. When it came to the latter, Ird had to consider the overcoming of differences of opinion within the theatre. A memorandum addressed to Ird by a representative of the younger generation – the young author Mati Unt, who worked at the theatre as a dramatist– in 1970 points to the shortfalls in the theatre’s repertoire policy, which did not ensure sufficient contact with the younger audience and did not find favour with the young Estonian directors who were seeking for theatre renewal. In the 1970s, Ird made corrections in this area by giving the young staff at the theatre free hands in the choice of texts to be staged, and protected their access to the stage before the control organs supervising stage productions (the ESSR Ministry of Culture and the censorship officials. Attempts at bringing the world classics of theatre to the stage were not as successful, and their proportion at the theatre was not large. However, the 1970s saw the attention of a significant number of young directors gravitate towards introducing the authors of drama classics (Ibsen, Strindberg, Brecht to the audience. The theatre focused less on the inclusion of contemporary Western dramas in the repertoire, the reason for this being the limited and strictly enforced quotas. When it came to the musical genres performed at the theatre (operas, operettas/musicals, ballets there was a noticeable preference for contemporary

  14. Repertoire of free-living protozoa in contact lens solutions.

    Science.gov (United States)

    Bouchoucha, Ibtissem; Aziz, Aurore; Hoffart, Louis; Drancourt, Michel

    2016-10-29

    The repertoire of free-living protozoa in contact lens solutions is poorly known despite the fact that such protozoa may act as direct pathogens and may harbor intra-cellular pathogens. Between 2009 and 2014, the contact lens solutions collected from patients presenting at our Ophthalmology Department for clinically suspected keratitis, were cultured on non-nutrient agar examined by microscope for the presence of free-living protozoa. All protozoa were identified by 18S rRNA gene sequencing. A total of 20 of 233 (8.6 %) contact lens solution specimens collected from 16 patients were cultured. Acanthamoeba amoeba in 16 solutions (80 %) collected from 12 patients and Colpoda steini, Cercozoa sp., Protostelium sp. and a eukaryotic more closely related to Vermamoeba sp., were each isolated in one solution. Cercozoa sp., Colpoda sp., Protostelium sp. and Vermamoeba sp. are reported for the first time as contaminating contact lens solutions. The repertoire of protozoa in contact lens solutions is larger than previously known.

  15. The repertoire and features of human platelet microRNAs.

    Directory of Open Access Journals (Sweden)

    Hélène Plé

    Full Text Available Playing a central role in the maintenance of hemostasis as well as in thrombotic disorders, platelets contain a relatively diverse messenger RNA (mRNA transcriptome as well as functional mRNA-regulatory microRNAs, suggesting that platelet mRNAs may be regulated by microRNAs. Here, we elucidated the complete repertoire and features of human platelet microRNAs by high-throughput sequencing. More than 492 different mature microRNAs were detected in human platelets, whereas the list of known human microRNAs was expanded further by the discovery of 40 novel microRNA sequences. As in nucleated cells, platelet microRNAs bear signs of post-transcriptional modifications, mainly terminal adenylation and uridylation. In vitro enzymatic assays demonstrated the ability of human platelets to uridylate microRNAs, which correlated with the presence of the uridyltransferase enzyme TUT4. We also detected numerous microRNA isoforms (isomiRs resulting from imprecise Drosha and/or Dicer processing, in some cases more frequently than the reference microRNA sequence, including 5' shifted isomiRs with redirected mRNA targeting abilities. This study unveils the existence of a relatively diverse and complex microRNA repertoire in human platelets, and represents a mandatory step towards elucidating the intraplatelet and extraplatelet role, function and importance of platelet microRNAs.

  16. FGF signaling repertoire of the indirect developing hemichordate Ptychodera flava.

    Science.gov (United States)

    Fan, Tzu-Pei; Su, Yi-Hsien

    2015-12-01

    Fibroblast growth factors (FGFs) are a group of ligands that play multiple roles during development by transducing signals through FGF receptors (FGFRs) to downstream factors. At least 22 FGF ligands and 4 receptors have been identified in vertebrates, while six to eight FGF ligands and a single FGFR are present in invertebrate chordates, such as tunicates and amphioxus. The chordate FGFs can be categorized into at least seven subfamilies, and the members of which expanded during the evolution of early vertebrates. In contrast, only one FGF and two FGFRs have been found in sea urchins. Thus, it is unclear whether the FGF subfamilies duplicated in the lineage leading to the chordates, or sea urchins lost several fgf genes. Analyses of the FGF signaling repertoire in hemichordates, which together with echinoderms form the closest group to the chordates, may provide insights into the evolution of FGF signaling in deuterostomes. In this study, we identified five FGFs and three FGFRs from Ptychodera flava, an indirect-developing hemichordate acorn worm. Phylogenetic analyses revealed that hemichordates possess a conserved FGF8/17/18 in addition to several putative hemichordate-specific FGFs. Analyses of sequence similarity and protein domain organizations suggested that the sea urchin and hemichordate FGFRs arose from independent lineage-specific duplications. Furthermore, the acorn worm fgf and fgfr genes were demonstrated to be expressed during P. flava embryogenesis. These results set the foundations for further functional studies of FGF signaling in hemichordates and provided insights into the evolutionary history of the FGF repertoire.

  17. The mimetic repertoire of the spotted bowerbird Ptilonorhynchus maculatus

    Science.gov (United States)

    Kelley, Laura A.; Healy, Susan D.

    2011-06-01

    Although vocal mimicry in songbirds is well documented, little is known about the function of such mimicry. One possibility is that the mimic produces the vocalisations of predatory or aggressive species to deter potential predators or competitors. Alternatively, these sounds may be learned in error as a result of their acoustic properties such as structural simplicity. We determined the mimetic repertoires of a population of male spotted bowerbirds Ptilonorhynchus maculatus, a species that mimics predatory and aggressive species. Although male mimetic repertoires contained an overabundance of vocalisations produced by species that were generally aggressive, there was also a marked prevalence of mimicry of sounds that are associated with alarm such as predator calls, alarm calls and mobbing calls, irrespective of whether the species being mimicked was aggressive or not. We propose that it may be the alarming context in which these sounds are first heard that may lead both to their acquisition and to their later reproduction. We suggest that enhanced learning capability during acute stress may explain vocal mimicry in many species that mimic sounds associated with alarm.

  18. Secondary Mechanisms of Affinity Maturation in the Human Antibody Repertoire

    Directory of Open Access Journals (Sweden)

    Bryan S. Briney

    2013-03-01

    Full Text Available V(DJ recombination and somatic hypermutation (SHM are the primary mechanisms for diversification of the human antibody repertoire. These mechanisms allow for rapid humoral immune responses to a wide range of pathogenic challenges. V(DJ recombination efficiently generate a virtually limitless diversity through random recombination of variable (V, diversity (D and joining (J genes with diverse nontemplated junctions between the selected gene segments. Following antigen stimulation, affinity maturation by SHM produces antibodies with refined specificity mediated by mutations typically focused in complementarity determining regions (CDRs, which form the bulk of the antigen recognition site. While V(DJ recombination and SHM are responsible for much of the diversity of the antibody repertoire, there are several secondary mechanisms that, while less frequent, make substantial contributions to antibody diversity including V(DDJ recombination (or D-D fusion, somatic-hypermutation-associated insertions and deletions, and affinity maturation and antigen contact by non-CDR regions of the antibody. In addition to enhanced diversity, these mechanisms allow the production of antibodies that are critical to response to a variety of viral and bacterial pathogens but that would be difficult to generate using only the primary mechanisms of diversification.

  19. Reconstructing and mining the B cell repertoire with ImmunediveRsity.

    Science.gov (United States)

    Cortina-Ceballos, Bernardo; Godoy-Lozano, Elizabeth Ernestina; Sámano-Sánchez, Hugo; Aguilar-Salgado, Andrés; Velasco-Herrera, Martín Del Castillo; Vargas-Chávez, Carlos; Velázquez-Ramírez, Daniel; Romero, Guillermo; Moreno, José; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús

    2015-01-01

    The B cell antigen receptor repertoire is highly diverse and constantly modified by clonal selection. High-throughput DNA sequencing (HTS) of the lymphocyte repertoire (Rep-Seq) represents a promising technology to explore such diversity ex-vivo and assist in the identification of antigen-specific antibodies based on molecular signatures of clonal selection. Therefore, integrative tools for repertoire reconstruction and analysis from antibody sequences are needed. We developed ImmunediveRity, a stand-alone pipeline primarily based in R programming for the integral analysis of B cell repertoire data generated by HTS. The pipeline integrates GNU software and in house scripts to perform quality filtering, sequencing noise correction and repertoire reconstruction based on V, D and J segment assignment, clonal origin and unique heavy chain identification. Post-analysis scripts generate a wealth of repertoire metrics that in conjunction with a rich graphical output facilitates sample comparison and repertoire mining. Its performance was tested with raw and curated human and mouse 454-Roche sequencing benchmarks providing good approximations of repertoire structure. Furthermore, ImmunediveRsity was used to mine the B cell repertoire of immunized mice with a model antigen, allowing the identification of previously validated antigen-specific antibodies, and revealing different and unexpected clonal diversity patterns in the post-immunization IgM and IgG compartments. Although ImmunediveRsity is similar to other recently developed tools, it offers significant advantages that facilitate repertoire analysis and repertoire mining. ImmunediveRsity is open source and free for academic purposes and it runs on 64 bit GNU/Linux and MacOS. Available at: https://bitbucket.org/ImmunediveRsity/immunediversity/.

  20. Characterization of neonatal vocal and motor repertoire of reelin mutant mice.

    Science.gov (United States)

    Romano, Emilia; Michetti, Caterina; Caruso, Angela; Laviola, Giovanni; Scattoni, Maria Luisa

    2013-01-01

    Reelin is a large secreted extracellular matrix glycoprotein playing an important role in early neurodevelopment. Several genetic studies found an association between RELN gene and increased risk of autism suggesting that reelin deficiency may be a vulnerability factor in its etiology. Moreover, a reduced reelin expression has been observed in several brain regions of subjects with Autism Spectrum Disorders. Since a number of reports have documented presence of vocal and neuromotor abnormalities in patients with autism and suggested that these dysfunctions predate the onset of the syndrome, we performed a fine-grain characterization of the neonatal vocal and motor repertoire in reelin mutant mice to explore the developmental precursors of the disorder. Our findings evidence a general delay in motor and vocal development in heterozygous (50% reduced reelin) and reeler (lacking reelin gene) mutant mice. As a whole, an increased number of calls characterized heterozygous pup's emission. Furthermore, the typical ontogenetic peak in the number of calls characterizing wild-type pups on postnatal day 4 appeared slightly delayed in heterozygous pups (to day 6) and was quite absent in reeler littermates, which exhibited a flat profile during development. We also detected a preferential use of a specific call category (two-components) by heterozygous and reeler mice at postnatal days 6 and 8 as compared to their wild-type littermates. With regard to the analysis of spontaneous movements, a differential profile emerged early in development among the three genotypes. While only slight coordination difficulties are exhibited by heterozygous pups, all indices of motor development appear delayed in reeler mice. Overall, our results evidence a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reelin mutant pups.

  1. Characterization of neonatal vocal and motor repertoire of reelin mutant mice.

    Directory of Open Access Journals (Sweden)

    Emilia Romano

    Full Text Available Reelin is a large secreted extracellular matrix glycoprotein playing an important role in early neurodevelopment. Several genetic studies found an association between RELN gene and increased risk of autism suggesting that reelin deficiency may be a vulnerability factor in its etiology. Moreover, a reduced reelin expression has been observed in several brain regions of subjects with Autism Spectrum Disorders. Since a number of reports have documented presence of vocal and neuromotor abnormalities in patients with autism and suggested that these dysfunctions predate the onset of the syndrome, we performed a fine-grain characterization of the neonatal vocal and motor repertoire in reelin mutant mice to explore the developmental precursors of the disorder. Our findings evidence a general delay in motor and vocal development in heterozygous (50% reduced reelin and reeler (lacking reelin gene mutant mice. As a whole, an increased number of calls characterized heterozygous pup's emission. Furthermore, the typical ontogenetic peak in the number of calls characterizing wild-type pups on postnatal day 4 appeared slightly delayed in heterozygous pups (to day 6 and was quite absent in reeler littermates, which exhibited a flat profile during development. We also detected a preferential use of a specific call category (two-components by heterozygous and reeler mice at postnatal days 6 and 8 as compared to their wild-type littermates. With regard to the analysis of spontaneous movements, a differential profile emerged early in development among the three genotypes. While only slight coordination difficulties are exhibited by heterozygous pups, all indices of motor development appear delayed in reeler mice. Overall, our results evidence a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reelin mutant pups.

  2. Does song repertoire size in Common Blackbirds play a role in an intra-sexual context?

    DEFF Research Database (Denmark)

    Hesler, Nana; Mundry, Roger; Dabelsteen, Torben

    2011-01-01

    Bird song is thought to have a function in both inter- and intra-sexual contexts with song complexity serving as an honest signal of male quality. Theory predicts that males use repertoire sizes to estimate rivals’ fighting ability. Here we tested whether element repertoire size plays a role in a...

  3. Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination

    Science.gov (United States)

    Jiang, Ning; He, Jiankui; Weinstein, Joshua A.; Penland, Lolita; Sasaki, Sanae; He, Xiao-Song; Dekker, Cornelia L.; Zheng, Nai-ying; Huang, Min; Sullivan, Meghan; Wilson, Patrick C.; Greenberg, Harry B.; Davis, Mark M.; Fisher, Daniel S.; Quake, Stephen R.

    2013-01-01

    The human antibody repertoire is one of the most important defenses against infectious disease, and the development of vaccines has enabled the conferral of targeted protection to specific pathogens. However, there are many challenges to measuring and analyzing the immunoglobulin sequence repertoire, such as the fact that each B cell contains a distinct antibody sequence encoded in its genome, that the antibody repertoire is not constant but changes over time, and the high similarity between antibody sequences. We have addressed this challenge by using high-throughput long read sequencing to perform immunogenomic characterization of expressed human antibody repertoires in the context of influenza vaccination. Informatic analysis of 5 million antibody heavy chain sequences from healthy individuals allowed us to perform global characterizations of isotype distributions, determine the lineage structure of the repertoire and measure age and antigen related mutational activity. Our analysis of the clonal structure and mutational distribution of individuals’ repertoires shows that elderly subjects have a decreased number of lineages but an increased pre-vaccination mutation load in their repertoire and that some of these subjects have an oligoclonal character to their repertoire in which the diversity of the lineages is greatly reduced relative to younger subjects. We have thus shown that global analysis of the immune system’s clonal structure provides direct insight into the effects of vaccination and provides a detailed molecular portrait of age-related effects. PMID:23390249

  4. Building the repertoire of measures of walking in Rett syndrome

    DEFF Research Database (Denmark)

    Stahlhut, Michelle; Downs, Jenny; Leonard, Helen;

    2017-01-01

    BACKGROUND: The repertoire of measures of walking in Rett syndrome is limited. This study aimed to determine measurement properties of a modified two-minute walk test (2MWT) and a modified Rett syndrome-specific functional mobility scale (FMS-RS) in Rett syndrome. METHODS: Forty-two girls and women...... with Rett syndrome (median 18.4 years, range 2.4-60.9 years) were assessed for clinical severity, gross motor skills, and mobility. To measure walking capacity, 27 of this group completed a 2MWT twice on two different assessment days. To assess walking performance, the FMS-RS was administered to the total......) and the Rett syndrome-specific functional mobility scale (FMS-RS). The 2MWT and FMS-RS offer detailed information of the capacity and performance of walking, respectively, in girls and women with RTT....

  5. The ancestral gene repertoire of animal stem cells.

    Science.gov (United States)

    Alié, Alexandre; Hayashi, Tetsutaro; Sugimura, Itsuro; Manuel, Michaël; Sugano, Wakana; Mano, Akira; Satoh, Nori; Agata, Kiyokazu; Funayama, Noriko

    2015-12-22

    Stem cells are pivotal for development and tissue homeostasis of multicellular animals, and the quest for a gene toolkit associated with the emergence of stem cells in a common ancestor of all metazoans remains a major challenge for evolutionary biology. We reconstructed the conserved gene repertoire of animal stem cells by transcriptomic profiling of totipotent archeocytes in the demosponge Ephydatia fluviatilis and by tracing shared molecular signatures with flatworm and Hydra stem cells. Phylostratigraphy analyses indicated that most of these stem-cell genes predate animal origin, with only few metazoan innovations, notably including several partners of the Piwi machinery known to promote genome stability. The ancestral stem-cell transcriptome is strikingly poor in transcription factors. Instead, it is rich in RNA regulatory actors, including components of the "germ-line multipotency program" and many RNA-binding proteins known as critical regulators of mammalian embryonic stem cells.

  6. Systematic comparative evaluation of methods for investigating the TCRβ repertoire

    DEFF Research Database (Denmark)

    Liu, Xiao; Zhang, Wei; Zeng, Xiaojing;

    2016-01-01

    advantages and disadvantages; however, a systematic evaluation and direct comparison of them would benefit researchers in the selection of the most suitable method. In this study, we used both pooled control plasmids and spiked-in cells to benchmark the MPCR bias. RNA from three healthy donors...... was subsequently processed with the two methods to perform a comparative evaluation of the TCR β chain sequences. Both approaches demonstrated high reproducibility (R2 = 0.9958 and 0.9878, respectively). No differences in gene usage were identified for most V/J genes (>60%), and an average of 52.03% of the CDR3...... variability was smaller compared with the biological variability. Through direct comparison, these findings provide novel insights into the two experimental methods, which will prove to be valuable in immune repertoire research and its interpretation....

  7. 不确定时变时滞退化系统的新鲁棒稳定性判据%Improved Delay-dependent Robust Stability Criteria for Descriptor Systems with Uncertain Time-varying Delay

    Institute of Scientific and Technical Information of China (English)

    程媛媛; 蒋威

    2012-01-01

    介绍了不确定时变时滞退化系统的一种新的鲁棒稳定性判据,该判据的提出利用适当的Lyapunov-Krasovskii函数方法,由一组线性矩阵不等式表示出来,判据可借助Matlab软件中LMI工具箱中得以验证.最后,数值实例证明了方法的有效性和优势.%This paper presents a new result of stability analysis for uncertain descriptor systems with time-varying delay,new delay-dependent robust stability criterion of uncertain time-delay descriptor systems is proposed by exploiting appropriate Lyapunov-Krasovskii functional candidate.This criterion is expressed by a set of linear matrix inequalities,which can be tested by using the LMI toolbox in Matlab.Finally,illustrative examples demonstrate the effectiveness and the advantage of the proposed method.

  8. Behavioural Repertoires and Time Budgets of Semi-Free-Ranging and Captive Groups of Wedge-Capped Capuchin Monkeys, Cebus olivaceus, in Zoo Exhibits in Venezuela.

    Science.gov (United States)

    Tárano, Zaida; López, Marie Charlotte

    2015-01-01

    The behavioural repertoires and time budgets of 2 captive groups and 1 semi-free-ranging group of Cebus olivaceus were determined with the aim to assess the impact of the zoo environment on behaviour. The repertoires were qualitatively similar between groups and to those reported for wild troops, but the captive groups showed self-directed and stereotyped behaviours not reported in the wild. The differences in repertoires between groups were easily associated with the opportunity to interact directly with the visitors, with particularities of the enclosure and with the severity of confinement. Overall, females spent more time foraging than males in the 2 captive groups, and adults rested and watched more than subadults in all the groups. Time budgets were dominated by foraging, resting, movement and affiliative interactions, but their relative importance varied between groups, with foraging being especially prominent in the most confined group. The time budgets also varied qualitatively from those reported for wild troops. We conclude the species is behaviourally able to adjust to captivity, but the slight differences along the continuum from wild to semi-free to captive are suggestive of mild stress or social tension probably due to unstimulating environmental conditions, high visitor pressure and deviations from typical sex-age group composition.

  9. "Is English Also the Place Where I Belong?": Linguistic Biographies and Expanding Communicative Repertoires in Central Java

    Science.gov (United States)

    Zentz, Lauren

    2015-01-01

    This article employs the term "communicative repertoire" in order to highlight that when one learns any new "language", one introduces new communicative resources into a unified communicative repertoire. As repertoires represent such singular "grammars" in individuals' minds, learned communicative resources can…

  10. "Is English Also the Place Where I Belong?": Linguistic Biographies and Expanding Communicative Repertoires in Central Java

    Science.gov (United States)

    Zentz, Lauren

    2015-01-01

    This article employs the term "communicative repertoire" in order to highlight that when one learns any new "language", one introduces new communicative resources into a unified communicative repertoire. As repertoires represent such singular "grammars" in individuals' minds, learned communicative resources can…

  11. Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection.

    Science.gov (United States)

    Taniguchi, Ruth T; DeVoss, Jason J; Moon, James J; Sidney, John; Sette, Alessandro; Jenkins, Marc K; Anderson, Mark S

    2012-05-15

    The autoimmune regulator (Aire) plays a critical role in central tolerance by promoting the display of tissue-specific antigens in the thymus. To study the influence of Aire on thymic selection in a physiological setting, we used tetramer reagents to detect autoreactive T cells specific for the Aire-dependent tissue-specific antigen interphotoreceptor retinoid-binding protein (IRBP), in the polyclonal repertoire. Two class II tetramer reagents were designed to identify T cells specific for two different peptide epitopes of IRBP. Analyses of the polyclonal T-cell repertoire showed a high frequency of activated T cells specific for both IRBP tetramers in Aire(-/-) mice, but not in Aire(+/+) mice. Surprisingly, although one tetramer-binding T-cell population was efficiently deleted in the thymus in an Aire-dependent manner, the second tetramer-binding population was not deleted and could be detected in both the Aire(-/-) and Aire(+/+) T-cell repertoires. We found that Aire-dependent thymic deletion of IRBP-specific T cells relies on intercellular transfer of IRBP between thymic stroma and bone marrow-derived antigen-presenting cells. Furthermore, our data suggest that Aire-mediated deletion relies not only on thymic expression of IRBP, but also on proper antigen processing and presentation of IRBP by thymic antigen-presenting cells.

  12. A Survey of the Gene Repertoire of Gigaspora rosea Unravels Conserved Features among Glomeromycota for Obligate Biotrophy.

    Science.gov (United States)

    Tang, Nianwu; San Clemente, Hélène; Roy, Sébastien; Bécard, Guillaume; Zhao, Bin; Roux, Christophe

    2016-01-01

    Arbuscular mycorrhizal (AM) fungi are a diverse group of soil fungi (Glomeromycota) that form the most ancient mutualistic association termed AM symbiosis with a majority of land plants, improving their nutrition uptake and resistance to stresses. In contrast to their great ecological implications, the knowledge of the molecular biological mechanisms involved is still scant, partly due to the limited genomic resources available. Here, we describe the gene repertoire of a new AM fungus Gigaspora rosea (Diversisporales). Among the 86332 non-redundant virtual transcripts assembled, 15346 presented similarities with proteins in the Refseq database and 10175 were assigned with GO terms. KOG and Interpro domain annotations clearly showed an enrichment of genes involved in signal transduction in G. rosea. KEGG pathway analysis indicates that most primary metabolic processes are active in G. rosea. However, as for Rhizophagus irregularis, several metabolic genes were not found, including the fatty acid synthase (FAS) gene. This finding supports the hypothesis that AM fungi depend on the lipids produced by their hosts. Furthermore, the presence of a large number of transporters and 100s of secreted proteins, together with the reduced number of plant cell wall degrading enzymes could be interpreted as an evolutionary adaptation to its mutualistic obligate biotrophy. The detection of meiosis-related genes suggests that G. rosea might use a cryptic sexual process. Lastly, a phylogeny of basal fungi clearly shows Glomeromycota as a sister clade to Mucoromycotina, not only to the Mucorales or Mortierellales. The characterization of the gene repertoire from an AM fungal species belonging to the order of Diversisporales and its comparison with the gene sets of R. irregularis (Glomerales) and Gigaspora margarita (Diversisporales), reveal that AM fungi share several features linked to mutualistic obligate biotrophy. This work contributes to lay the foundation for forthcoming studies

  13. A survey of the gene repertoire of Gigaspora rosea unravels conserved features among Glomeromycota for obligate biotrophy

    Directory of Open Access Journals (Sweden)

    Nianwu eTANG

    2016-03-01

    Full Text Available Arbuscular mycorrhizal (AM fungi are a diverse group of soil fungi (Glomeromycota that form the most ancient mutualistic association termed arbuscular mycorrhizal symbiosis with a majority of land plants, improving their nutrition uptake and resistance to stresses. In contrast to their great ecological implications, the knowledge of the molecular biological mechanisms involved is still scant, partly due to the limited genomic resources available. Here, we describe the gene repertoire of a new AM fungus Gigaspora rosea (Diversisporales. Among the 86332 nonredundant virtual transcripts assembled, 15346 presented similarities with proteins in the Refseq database and 10175 were assigned with GO terms. KOG and Interpro domain annotations clearly showed an enrichment of genes involved in signal transduction in G. rosea. KEGG pathway analysis indicates that most primary metabolic processes are active in G. rosea. However, as for R. irregularis, several metabolic genes were not found, including the fatty acid synthase gene. This finding supports the hypothesis that AM fungi depend on the lipids produced by their hosts. Furthermore, the presence of a large number of transporters and hundreds of secreted proteins, together with the reduced number of plant cell wall degrading enzymes could be interpreted as an evolutionary adaptation to its mutualistic obligate biotrophy. The detection of meiosis-related genes suggests that G. rosea might use a cryptic sexual process. Lastly, a phylogeny of basal fungi clearly shows Glomeromycota as a sister clade to Mucoromycotina, not only to the Mucorales or Mortierellales. The characterization of the gene repertoire from an AM fungal species belonging to the order of Diversisporales and its comparison with the gene sets of R. irregularis (Glomerales and Gigaspora margarita (Diversisporales, reveal that AM fungi share several features linked to mutualistic obligate biotrophy. This work contributes to lay the foundation

  14. The repertoire of equine intestinal α-defensins

    Directory of Open Access Journals (Sweden)

    Tetens Jens

    2009-12-01

    Full Text Available Abstract Background Defensins represent an important class of antimicrobial peptides. These effector molecules of the innate immune system act as endogenous antibiotics to protect the organism against infections with pathogenic microorganisms. Mammalian defensins are classified into three distinct sub-families (α-, β- and θ-defensins according to their specific intramolecular disulfide-bond pattern. The peptides exhibit an antimicrobial activity against a broad spectrum of microorganisms including bacteria and fungi. Alpha-Defensins are primarily synthesised in neutrophils and intestinal Paneth cells. They play a role in the pathogenesis of intestinal diseases and may regulate the flora of the intestinal tract. An equine intestinal α-defensin (DEFA1, the first characterised in the Laurasiatheria, shows a broad antimicrobial spectrum against human and equine pathogens. Here we report a first investigation of the repertoire of equine intestinal α-defensins. The equine genome was screened for putative α-defensin genes by using known α-defensin sequences as matrices. Based on the obtained sequence information, a set of oligonucleotides specific to the α-defensin gene-family was designed. The products generated by reverse-transcriptase PCR with cDNA from the small intestine as template were sub-cloned and numerous clones were sequenced. Results Thirty-eight equine intestinal α-defensin transcripts were determined. After translation it became evident that at least 20 of them may code for functional peptides. Ten transcripts lacked matching genomic sequences and for 14 α-defensin genes apparently present in the genome no appropriate transcript could be verified. In other cases the same genomic exons were found in different transcripts. Conclusions The large repertoire of equine α-defensins found in this study points to a particular importance of these peptides regarding animal health and protection from infectious diseases. Moreover, these

  15. Song repertoire size correlates with measures of body size in Eurasian blackbirds

    DEFF Research Database (Denmark)

    Hesler, Nana; Mundry, Roger; Sacher, Thomas;

    2012-01-01

    organisation. Here we investigated whether repertoire size in Eurasian blackbirds correlates with measures of body size, namely length of wing, 8th primary, beak and tarsus. So far, very few studies have investigated species with large repertoires and a flexible song organisation in this context. We found...... positive correlations, meaning that larger males had larger repertoires. Larger males may have better fighting abilities and, thus, advantages in territorial defence. Larger structural body size may also reflect better conditions during early development. Therefore, under the assumption that body size...

  16. Gene repertoire of amoeba-associated giant viruses.

    Science.gov (United States)

    Colson, Philippe; Raoult, Didier

    2010-01-01

    Acanthamoeba polyphaga mimivirus, Marseillevirus, and Sputnik, a virophage, are intra-amoebal viruses that have been isolated from water collected in cooling towers. They have provided fascinating data and have raised exciting questions about viruses definition and evolution. Mimivirus and Marseillevirus have been classified in the nucleo-cytoplasmic large DNA viruses (NCLDVs) class. Their genomes are the largest and fifth largest viral genomes sequenced so far. The gene repertoire of these amoeba-associated viruses can be divided into four groups: the core genome, genes acquired by lateral gene transfer, duplicated genes, and ORFans. Open reading frames (ORFs) that have homologs in the NCLDVs core gene set represent 2.9 and 6.1% of the Mimivirus and Marseillevirus gene contents, respectively. A substantial proportion of the Mimivirus, Marseillevirus and Sputnik ORFs exhibit sequence similarities to homologs found in bacteria, archaea, eukaryotes or viruses. The large amount of chimeric genes in these viral genomes might have resulted from acquisitions by lateral gene transfers, implicating sympatric bacteria and viruses with an intra-amoebal lifestyle. In addition, lineage-specific gene expansion may have played a major role in the genome shaping. Altogether, the data so far accumulated on amoeba-associated giant viruses are a powerful incentive to isolate and study additional strains to gain better understanding of their pangenome.

  17. Comprehensive repertoire of foldable regions within whole genomes.

    Directory of Open Access Journals (Sweden)

    Guilhem Faure

    2013-10-01

    Full Text Available In order to get a comprehensive repertoire of foldable domains within whole proteomes, including orphan domains, we developed a novel procedure, called SEG-HCA. From only the information of a single amino acid sequence, SEG-HCA automatically delineates segments possessing high densities in hydrophobic clusters, as defined by Hydrophobic Cluster Analysis (HCA. These hydrophobic clusters mainly correspond to regular secondary structures, which together form structured or foldable regions. Genome-wide analyses revealed that SEG-HCA is opposite of disorder predictors, both addressing distinct structural states. Interestingly, there is however an overlap between the two predictions, including small segments of disordered sequences, which undergo coupled folding and binding. SEG-HCA thus gives access to these specific domains, which are generally poorly represented in domain databases. Comparison of the whole set of SEG-HCA predictions with the Conserved Domain Database (CDD also highlighted a wide proportion of predicted large (length >50 amino acids segments, which are CDD orphan. These orphan sequences may either correspond to highly divergent members of already known families or belong to new families of domains. Their comprehensive description thus opens new avenues to investigate new functional and/or structural features, which remained so far uncovered. Altogether, the data described here provide new insights into the protein architecture and organization throughout the three kingdoms of life.

  18. Systematic Comparative Evaluation of Methods for Investigating the TCRβ Repertoire.

    Science.gov (United States)

    Liu, Xiao; Zhang, Wei; Zeng, Xiaojing; Zhang, Ruifang; Du, Yuanping; Hong, Xueyu; Cao, Hongzhi; Su, Zheng; Wang, Changxi; Wu, Jinghua; Nie, Chao; Xu, Xun; Kristiansen, Karsten

    2016-01-01

    High-throughput sequencing has recently been applied to profile the high diversity of antibodyome/B cell receptors (BCRs) and T cell receptors (TCRs) among immune cells. To date, Multiplex PCR (MPCR) and 5'RACE are predominately used to enrich rearranged BCRs and TCRs. Both approaches have advantages and disadvantages; however, a systematic evaluation and direct comparison of them would benefit researchers in the selection of the most suitable method. In this study, we used both pooled control plasmids and spiked-in cells to benchmark the MPCR bias. RNA from three healthy donors was subsequently processed with the two methods to perform a comparative evaluation of the TCR β chain sequences. Both approaches demonstrated high reproducibility (R2 = 0.9958 and 0.9878, respectively). No differences in gene usage were identified for most V/J genes (>60%), and an average of 52.03% of the CDR3 amino acid sequences overlapped. MPCR exhibited a certain degree of bias, in which the usage of several genes deviated from 5'RACE, and some V-J pairings were lost. In contrast, there was a smaller rate of effective data from 5'RACE (11.25% less compared with MPCR). Nevertheless, the methodological variability was smaller compared with the biological variability. Through direct comparison, these findings provide novel insights into the two experimental methods, which will prove to be valuable in immune repertoire research and its interpretation.

  19. Systematic Comparative Evaluation of Methods for Investigating the TCRβ Repertoire.

    Directory of Open Access Journals (Sweden)

    Xiao Liu

    Full Text Available High-throughput sequencing has recently been applied to profile the high diversity of antibodyome/B cell receptors (BCRs and T cell receptors (TCRs among immune cells. To date, Multiplex PCR (MPCR and 5'RACE are predominately used to enrich rearranged BCRs and TCRs. Both approaches have advantages and disadvantages; however, a systematic evaluation and direct comparison of them would benefit researchers in the selection of the most suitable method. In this study, we used both pooled control plasmids and spiked-in cells to benchmark the MPCR bias. RNA from three healthy donors was subsequently processed with the two methods to perform a comparative evaluation of the TCR β chain sequences. Both approaches demonstrated high reproducibility (R2 = 0.9958 and 0.9878, respectively. No differences in gene usage were identified for most V/J genes (>60%, and an average of 52.03% of the CDR3 amino acid sequences overlapped. MPCR exhibited a certain degree of bias, in which the usage of several genes deviated from 5'RACE, and some V-J pairings were lost. In contrast, there was a smaller rate of effective data from 5'RACE (11.25% less compared with MPCR. Nevertheless, the methodological variability was smaller compared with the biological variability. Through direct comparison, these findings provide novel insights into the two experimental methods, which will prove to be valuable in immune repertoire research and its interpretation.

  20. Schizophyllum commune has an extensive and functional alternative splicing repertoire.

    Science.gov (United States)

    Gehrmann, Thies; Pelkmans, Jordi F; Lugones, Luis G; Wösten, Han A B; Abeel, Thomas; Reinders, Marcel J T

    2016-09-23

    Recent genome-wide studies have demonstrated that fungi possess the machinery to alternatively splice pre-mRNA. However, there has not been a systematic categorization of the functional impact of alternative splicing in a fungus. We investigate alternative splicing and its functional consequences in the model mushroom forming fungus Schizophyllum commune. Alternative splicing was demonstrated for 2,285 out of 12,988 expressed genes, resulting in 20% additional transcripts. Intron retentions were the most common alternative splicing events, accounting for 33% of all splicing events, and 43% of the events in coding regions. On the other hand, exon skipping events were rare in coding regions (1%) but enriched in UTRs where they accounted for 57% of the events. Specific functional groups, including transcription factors, contained alternatively spliced genes. Alternatively spliced transcripts were regulated differently throughout development in 19% of the 2,285 alternatively spliced genes. Notably, 69% of alternatively spliced genes have predicted alternative functionality by loss or gain of functional domains, or by acquiring alternative subcellular locations. S. commune exhibits more alternative splicing than any other studied fungus. Taken together, alternative splicing increases the complexity of the S. commune proteome considerably and provides it with a rich repertoire of alternative functionality that is exploited dynamically.

  1. Criticism of TV in Brazil: values and repertoires

    Directory of Open Access Journals (Sweden)

    Rosana Soares

    2013-07-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 TV criticism in cultural journalism faces nowadays some challenges for programming evaluation, among them, the set up of a repertoire. This article aims at identifying, and discussing the values (aesthetical, market, pedagogical which are raised in critical texts written by the journalists Patricia Kogut, from O Globo, and Daniel Castro, from the internet portal R7. Results obtained indicate that Kogut´s criticism favours the examination of television narrative discourse while Castro´s privileges aspects related mainly to the audience. As common points, both sets of critical texts share values related to innovation, interactivity, and transmediality as parameters for a quality TV. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabela normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}

  2. A Survey on Current Repertoire for 5G

    Directory of Open Access Journals (Sweden)

    Muhammad Aamir Nadeem

    2017-02-01

    Full Text Available Cellular technology progressed miraculously in the last decade. It has redefined communication paradigm. Statistics provided by Ericson and Cisco show the number of mobile connected devices will reach figures of 9.2 billion and 11.6 billion respectively by 2020. Overall connected devices will surpass 50 billion then. Extremely higher data rates, zero latency, massively scalable, connecting everything anywhere is what that 5G promises. To meet such ambitious goals which apparently seems challenging, the tools and technologies that mobile communication has in its repertoire and what it needs more either enhancement in existing solutions or new solution or joint venture of both, is a question that demands an answer. To realize 5G, evolution and revolution both approaches are being employed. Evolution seeks enhancements in existing technologies while revolution looks for new innovations and technologies. Extension in frequency spectrum, network densification, MIMO, carrier aggregation, CentralizedRAN, HetNets, and Network Functionality Virtualization are the key enablers. This paper disseminates information about ongoing research and development of 5G

  3. The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44.

    Science.gov (United States)

    Perfetti, Vittorio; Palladini, Giovanni; Casarini, Simona; Navazza, Valentina; Rognoni, Paola; Obici, Laura; Invernizzi, Rosangela; Perlini, Stefano; Klersy, Catherine; Merlini, Giampaolo

    2012-01-05

    Monoclonal Ig light chains (LC) can be responsible for pathologic conditions in humans, as in systemic amyloid light amyloidosis. Protean clinical manifestations characterize this disorder with the most varied combination of symptoms generated by different degrees of diverse organ involvement. Kidney and heart are most frequently interested, with major heart involvement as the most relevant prognostic factor. The identification of the underlying mechanism involved in organ targeting is of major relevance for the pathobiology of this disorder. To this aim, we characterized the repertoire of variable region germline genes of λ LC preferentially targeting the heart and compared it with the repertoire of LC that do not in a case-control study. We found that the repertoires were highly restricted, showing preferential use of the same few germline genes but with a different frequency pattern. A single gene, IGVL1-44, was found associated with a 5-fold increase in the odds of dominant heart involvement (after adjusting for confounders in a multivariable logistic model). These results support an involvement of LC genetics in the determination of organ targeting. Study of the characteristics of IGVL1-44-LC with, and of the minority without, heart involvement might lead to identification of LC/tissue interactions.

  4. Defining the alloreactive T cell repertoire using high-throughput sequencing of mixed lymphocyte reaction culture.

    Directory of Open Access Journals (Sweden)

    Ryan O Emerson

    Full Text Available The cellular immune response is the most important mediator of allograft rejection and is a major barrier to transplant tolerance. Delineation of the depth and breadth of the alloreactive T cell repertoire and subsequent application of the technology to the clinic may improve patient outcomes. As a first step toward this, we have used MLR and high-throughput sequencing to characterize the alloreactive T cell repertoire in healthy adults at baseline and 3 months later. Our results demonstrate that thousands of T cell clones proliferate in MLR, and that the alloreactive repertoire is dominated by relatively high-abundance T cell clones. This clonal make up is consistently reproducible across replicates and across a span of three months. These results indicate that our technology is sensitive and that the alloreactive TCR repertoire is broad and stable over time. We anticipate that application of this approach to track donor-reactive clones may positively impact clinical management of transplant patients.

  5. Dolce Napoli : approaches for performance - Recorders for the Neapolitan Baroque repertoire, 1695-1759

    NARCIS (Netherlands)

    de Avena Braga, Inês

    2015-01-01

    This thesis examined two previously neglected topics, Baroque Italian recorders and the Neapolitan Baroque repertoire for the recorder, and then combined both aspects. First, information was collected on all Italian Baroque recorders currently known, including biographical refere

  6. Natural and man-made V-gene repertoires for antibody discovery.

    Science.gov (United States)

    Finlay, William J J; Almagro, Juan C

    2012-01-01

    Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety, and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of humans, mice, and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity, and composition of a repertoire impact the antibody discovery process.

  7. The vocal repertoire of the African Penguin (Spheniscus demersus): structure and function of calls

    National Research Council Canada - National Science Library

    Favaro, Livio; Ozella, Laura; Pessani, Daniela

    2014-01-01

    The African Penguin (Spheniscus demersus) is a highly social and vocal seabird. However, currently available descriptions of the vocal repertoire of African Penguin are mostly limited to basic descriptions of calls...

  8. Reading YES: Interpretive repertoires and identity construction in Dutch teenage magazines

    NARCIS (Netherlands)

    Hijmans, E.J.S.

    2004-01-01

    Analysis of interviews with Dutch teenage readers of the teenage girls’ magazine Yes demonstrates various ways in which girls use media content to construct gender identity. Theoretical concepts drawn from a symbolic interactionist perspective and reconstruction of interpretive repertoires illustra

  9. Characterizing Vocal Repertoires--Hard vs. Soft Classification Approaches: e0125785

    National Research Council Canada - National Science Library

    Philip Wadewitz; Kurt Hammerschmidt; Demian Battaglia; Annette Witt; Fred Wolf; Julia Fischer

    2015-01-01

      To understand the proximate and ultimate causes that shape acoustic communication in animals, objective characterizations of the vocal repertoire of a given species are critical, as they provide...

  10. Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire

    National Research Council Canada - National Science Library

    Passilongo, Daniela; Reby, David; Carranza, Juan; Apollonio, Marco

    2013-01-01

    .... We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies...

  11. Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing.

    Science.gov (United States)

    Vander Heiden, Jason A; Stathopoulos, Panos; Zhou, Julian Q; Chen, Luan; Gilbert, Tamara J; Bolen, Christopher R; Barohn, Richard J; Dimachkie, Mazen M; Ciafaloni, Emma; Broering, Teresa J; Vigneault, Francois; Nowak, Richard J; Kleinstein, Steven H; O'Connor, Kevin C

    2017-02-15

    Myasthenia gravis (MG) is a prototypical B cell-mediated autoimmune disease affecting 20-50 people per 100,000. The majority of patients fall into two clinically distinguishable types based on whether they produce autoantibodies targeting the acetylcholine receptor (AChR-MG) or muscle specific kinase (MuSK-MG). The autoantibodies are pathogenic, but whether their generation is associated with broader defects in the B cell repertoire is unknown. To address this question, we performed deep sequencing of the BCR repertoire of AChR-MG, MuSK-MG, and healthy subjects to generate ∼518,000 unique VH and VL sequences from sorted naive and memory B cell populations. AChR-MG and MuSK-MG subjects displayed distinct gene segment usage biases in both VH and VL sequences within the naive and memory compartments. The memory compartment of AChR-MG was further characterized by reduced positive selection of somatic mutations in the VH CDR and altered VH CDR3 physicochemical properties. The VL repertoire of MuSK-MG was specifically characterized by reduced V-J segment distance in recombined sequences, suggesting diminished VL receptor editing during B cell development. Our results identify large-scale abnormalities in both the naive and memory B cell repertoires. Particular abnormalities were unique to either AChR-MG or MuSK-MG, indicating that the repertoires reflect the distinct properties of the subtypes. These repertoire abnormalities are consistent with previously observed defects in B cell tolerance checkpoints in MG, thereby offering additional insight regarding the impact of tolerance defects on peripheral autoimmune repertoires. These collective findings point toward a deformed B cell repertoire as a fundamental component of MG.

  12. Temporal regularity increases with repertoire complexity in the Australian pied butcherbird's song

    Science.gov (United States)

    Taylor, Hollis; Scharff, Constance; Rothenberg, David; Parra, Lucas C.; Tchernichovski, Ofer

    2016-01-01

    Music maintains a characteristic balance between repetition and novelty. Here, we report a similar balance in singing performances of free-living Australian pied butcherbirds. Their songs include many phrase types. The more phrase types in a bird's repertoire, the more diverse the singing performance can be. However, without sufficient temporal organization, avian listeners may find diverse singing performances difficult to perceive and memorize. We tested for a correlation between the complexity of song repertoire and the temporal regularity of singing performance. We found that different phrase types often share motifs (notes or stereotyped groups of notes). These shared motifs reappeared in strikingly regular temporal intervals across different phrase types, over hundreds of phrases produced without interruption by each bird. We developed a statistical estimate to quantify the degree to which phrase transition structure is optimized for maximizing the regularity of shared motifs. We found that transition probabilities between phrase types tend to maximize regularity in the repetition of shared motifs, but only in birds of high repertoire complexity. Conversely, in birds of low repertoire complexity, shared motifs were produced with less regularity. The strong correlation between repertoire complexity and motif regularity suggests that birds possess a mechanism that regulates the temporal placement of shared motifs in a manner that takes repertoire complexity into account. We discuss alternative musical, mechanistic and ecological explanations to this effect. PMID:27703699

  13. Differences in the composition of the human antibody repertoire by B cell subsets in the blood

    Directory of Open Access Journals (Sweden)

    Eva Szymanska eMroczek

    2014-03-01

    Full Text Available The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V (D J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N- region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth comparison of V (D J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between heavy chain repertoires expressed by immature, transitional, mature, memory IgD+, memory IgD-, and plasmacytes isolated from the blood of a single individual. Our results support the view that in both human and mouse the H chain repertoires expressed by individual, developmental B cell subsets appear to differ in sequence content. Sequencing of unsorted B cells from the blood is thus likely to yield an incomplete or compressed view of what is actually happening in the immune response of the individual. Our findings support the view that studies designed to correlate repertoire expression with diseases of immune function will likely require deep sequencing of B cells sorted by subset.

  14. Intratumoral convergence of the TCR repertoires of effector and Foxp3+ CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Michal Kuczma

    Full Text Available The presence of Foxp3(+ regulatory CD4(+ T cells in tumor lesions is considered one of the major causes of ineffective immune response in cancer. It is not clear whether intratumoral T(reg cells represent T(reg cells pre-existing in healthy mice, or arise from tumor-specific effector CD4(+ T cells and thus representing adaptive T(reg cells. The generation of T(reg population in tumors could be further complicated by recent evidence showing that both in humans and mice the peripheral population of T(reg cells is heterogenous and consists of subsets which may differentially respond to tumor-derived antigens. We have studied T(reg cells in cancer in experimental mice that express naturally selected, polyclonal repertoire of CD4(+ T cells and which preserve the heterogeneity of the T(reg population. The majority of T(reg cells present in healthy mice maintained a stable suppressor phenotype, expressed high level of Foxp3 and an exclusive set of TCRs not used by naive CD4(+ T cells. A small T(reg subset, utilized TCRs shared with effector T cells and expressed a lower level of Foxp3. We show that response to tumor-derived antigens induced efficient clonal recruitment and expansion of antigen-specific effector and T(reg cells. However, the population of T(reg cells in tumors was dominated by cells expressing TCRs shared with effector CD4(+ T cells. In contrast, T(reg cells expressing an exclusive set of TCRs, that dominate in healthy mice, accounted for only a small fraction of all T(reg cells in tumor lesions. Our results suggest that the T(reg repertoire in tumors is generated by conversion of effector CD4(+ T cells or expansion of a minor subset of T(reg cells. In conclusion, successful cancer immunotherapy may depend on the ability to block upregulation of Foxp3 in effector CD4(+ T cells and/or selectively inhibiting the expansion of a minor T(reg subset.

  15. Abacavir and the altered peptide repertoire model: clinical implications

    Directory of Open Access Journals (Sweden)

    Mallal S

    2012-11-01

    Full Text Available Structural and biochemical studies showing that abacavir binds non-covalently to the floor of the peptide binding groove of HLA-B*5701 with exquisite specificity to alter the self-peptides that load on the molecule to be presented to the immune system have recently been published [1–4]. This precise mechanistic explanation of why abacavir binds to HLA-B*5701 and no other allele accounts for the 100% negative predictive value of HLA-B*5701 testing for hypersensitivity which underpins its utility as a screening test. The specificity of the interaction between abacavir, peptide and HLA-B*5701 provides strong evidence that abacavir will not cause any off-target, HLA restricted immune-mediated side effects in HLA-B*5701 negative individuals. The rapid and direct non-covalent binding of abacavir to HLA-B*5701 without the requirement for metabolism of the drug explain the clinical symptoms of hypersensitivity including dose-related escalation of symptoms and rapid offset of symptoms following drug cessation. Importantly, if abacavir were being developed today its propensity to bind HLA-B*5701, alter the peptide repertoire presented, and the functional consequences of this interaction between HLA-B*5701 and abacavir could be determined in vitro and before use in man. This provides an important pre-clinical screening strategy to identify compounds in development that bind HLA and alter peptide presentation which could then be structurally modified to abrogate this property to avert hypersensitivity while retaining on-target effects.

  16. Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation.

    Science.gov (United States)

    Dagklis, A; Ponzoni, M; Govi, S; Cangi, M G; Pasini, E; Charlotte, F; Vino, A; Doglioni, C; Davì, F; Lossos, I S; Ntountas, I; Papadaki, T; Dolcetti, R; Ferreri, A J M; Stamatopoulos, K; Ghia, P

    2012-04-01

    Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

  17. An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus

    Science.gov (United States)

    Nguyen, Thi-Minh; Schreiner, Dietmar; Xiao, Le; Traunmüller, Lisa; Bornmann, Caroline; Scheiffele, Peter

    2016-01-01

    The unique anatomical and functional features of principal and interneuron populations are critical for the appropriate function of neuronal circuits. Cell type-specific properties are encoded by selective gene expression programs that shape molecular repertoires and synaptic protein complexes. However, the nature of such programs, particularly for post-transcriptional regulation at the level of alternative splicing is only beginning to emerge. We here demonstrate that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing. Principal cell-specific neurexin splice isoforms depend on the RNA-binding protein Slm2. By contrast, most parvalbumin-positive (PV+) interneurons lack Slm2, express a different neurexin splice isoform and co-express the corresponding splice isoform-specific neurexin ligand Cbln4. Conditional ablation of Nrxn alternative splice insertions selectively in PV+ cells results in elevated hippocampal network activity and impairment in a learning task. Thus, PV-cell-specific alternative splicing of neurexins is critical for neuronal circuit function DOI: http://dx.doi.org/10.7554/eLife.22757.001 PMID:27960072

  18. Directed evolution of artificial enzymes (XNAzymes) from diverse repertoires of synthetic genetic polymers.

    Science.gov (United States)

    Taylor, Alexander I; Holliger, Philipp

    2015-10-01

    This protocol describes the directed evolution of artificial endonuclease and ligase enzymes composed of synthetic genetic polymers (XNAzymes), using 'cross-chemistry selective enrichment by exponential amplification' (X-SELEX). The protocol is analogous to (deoxy)ribozyme selections, but it enables the development of fully substituted catalysts. X-SELEX is initiated by the synthesis of diverse repertoires (here 10(14) different sequences), using xeno nucleic acid (XNA) polymerases, on DNA templates primed with DNA, RNA or XNA oligonucleotides that double as substrates, allowing selection for XNA-catalyzed cleavage or ligation. XNAzymes are reverse-transcribed into cDNA using XNA-dependent DNA polymerases, and then PCR-amplified to generate templates for subsequent rounds or deep sequencing. We describe methods developed for four XNA chemistries, arabino nucleic acids (ANAs), 2'-fluoroarabino nucleic acids (FANAs), hexitol nucleic acids (HNAs) and cyclohexene nucleic acids (CeNAs), which require ∼1 week per round, and typically 10-20 rounds; in principle, these methods are scalable and applicable to a wide range of novel XNAzyme chemistries, substrates and reactions.

  19. Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

    Directory of Open Access Journals (Sweden)

    Ilja V. Khavrutskii

    2017-08-01

    Full Text Available Recent advances in the next-generation sequencing of B-cell receptors (BCRs enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 103–105 sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative trends in immunoglobulin (Ig properties, such as usage or somatic hypermutation (SHM percentage of the Ig heavy chain variable (IGHV gene segment family, and on reducing complex Ig property distributions to simple summary statistics. However, because Ig properties are typically not normally distributed, any approach that fails to assess the distribution as a whole may be inadequate in (1 properly assessing the statistical significance of repertoire differences, (2 identifying how two repertoires differ, and (3 determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance. To address these issues, we have developed a technique that uses Wilcox’ robust statistics toolbox to identify statistically significant vaccine-specific differences between Ig repertoire properties. The advantage of this technique is that it can determine not only whether but also where the distributions differ, even when the Ig repertoire properties are non-normally distributed. We used this technique to characterize murine germinal center (GC B-cell repertoires in response to a complex Ebola virus-like particle (eVLP vaccine candidate with known protective efficacy. The eVLP-mediated GC B-cell responses were highly diverse, consisting of thousands of clonotypes. Despite this staggering diversity, we identified statistically

  20. Time Varying Feature Data

    Science.gov (United States)

    Echterhoff, J.; Simonis, I.; Atkinson, R.

    2012-04-01

    The infrastructure to gather, store and access information about our environment is improving and growing rapidly. The increasing amount of information allows us to get a better understanding of the current state of our environment, historical processes and to simulate and predict the future state of the environment. Finer grained spatial and temporal data and more reliable communications make it easier to model dynamic states and ephemeral features. The exchange of information within and across geospatial domains is facilitated through the use of harmonized information models. The Observations & Measurements (O&M) developed through OGC and standardised by ISO is an example of such a cross-domain information model. It is used in many domains, including meteorology, hydrology as well as the emergency management. O&M enables harmonized representation of common metadata that belong to the act of determining the state of a feature property, whether by sensors, simulations or humans. In addition to the resulting feature property value, information such as the result quality but especially the time that the result applies to the feature property can be represented. Temporal metadata is critical to modelling past and future states of a feature. The features, and the semantics of each property, are defined in domain specific Application Schema using the General Feature Model (GFM) from ISO 19109 and usually encoded following ISO 19136. However, at the moment these standards provide only limited support for the representation and handling of time varying feature data. Features like rivers, wildfires or gas plumes have a defined state - for example geographic extent - at any given point in time. To keep track of changes, a more complex model for example using time-series coverages is required. Furthermore, the representation and management of feature property value changes via the service interfaces defined by OGC and ISO - namely: WFS and WCS - would be rather complex

  1. A theoretical interpersonal style repertoire for middle-level managers

    Directory of Open Access Journals (Sweden)

    P. Koortzen

    2005-10-01

    Full Text Available The development of the interpersonal behaviour of managers has received a good deal of attention, especially in terms of the most appropriate interpersonal styles in the work context and the skills involved in developing and maintaining effective interpersonal relationships. The design of effective interpersonal development programs requires a thorough evaluation of an individual’s interpersonal development needs. In order to do this, evaluators should have an understanding of the most appropriate interpersonal styles for managers. Given the aims of the investigation, the approach that was followed was to evaluate the relevant literature in this field. The theoretical goal was to study and describe the most appropriate theoretical interpersonal style repertoire of middle-level managers using the interpersonal approach, and specifically the 1982 Interpersonal Circle. The conclusions support the notion that dominant, assured, exhibitionistic, social, friendly, warm and trusting styles are the most relevant of the 16 interpersonal segments, while the assured-dominant, social-exhibitionistic and warm-friendly octants are viewed as the most appropriate. Opsomming Die ontwikkeling van die interpersoonlike gedrag van bestuurders het reeds heelwat aandag gekry. Dit geld veral vir aangeleenthede wat verband hou met die mees toepaslike interpersoonlike style binne die werkskonteks en die vaardighede wat die ontwikkeling van effektiewe interpersoonlike verhoudings onderlê. Die ontwikkeling van effektiewe interpersoonlike ontwikkelingsprogramme vereis ’n deeglike evaluering van ’n individu se interpersoonlike ontwikkelingsbehoeftes. Om dit te vermag, is dit nodig vir evalueerders om te verstaan wat die mees toepaslike interpersoonlike style vir bestuurders is. Gegee die doelwitte van die ondersoek is die metode wat gevolg is ’n evaluering van die relevante literatuur in hierdie gebied. Die teoretiese doel was om die mees toepaslike teoretiese

  2. Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients

    Science.gov (United States)

    Hou, Dongni; Ying, Tianlei; Wang, Lili; Chen, Cuicui; Lu, Shuihua; Wang, Qin; Seeley, Eric; Xu, Jianqing; Xi, Xiuhong; Li, Tao; Liu, Jie; Tang, Xinjun; Zhang, Zhiyong; Zhou, Jian; Bai, Chunxue; Wang, Chunlin; Byrne-Steele, Miranda; Qu, Jieming; Han, Jian; Song, Yuanlin

    2016-01-01

    Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways – higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection. PMID:27669665

  3. Murinization of internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses.

    Directory of Open Access Journals (Sweden)

    Yu-Huan Tsai

    Full Text Available Listeria monocytogenes (Lm is an invasive foodborne pathogen that leads to severe central nervous system and maternal-fetal infections. Lm ability to actively cross the intestinal barrier is one of its key pathogenic properties. Lm crosses the intestinal epithelium upon the interaction of its surface protein internalin (InlA with its host receptor E-cadherin (Ecad. InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been "murinized" to interact with mouse Ecad. Here, we demonstrate that, unexpectedly, murinized InlA (InlA(m mediates not only Ecad-dependent internalization, but also N-cadherin-dependent internalization. Consequently, InlA(m-expressing Lm targets not only goblet cells expressing luminally-accessible Ecad, as does Lm in humanized mice, but also targets villous M cells, which express luminally-accessible N-cadherin. This aberrant Lm portal of entry results in enhanced innate immune responses and intestinal barrier damage, both of which are not observed in wild-type Lm-infected humanized mice. Murinization of InlA therefore not only extends the host range of Lm, but also broadens its receptor repertoire, providing Lm with artifactual pathogenic properties. These results challenge the relevance of using InlA(m-expressing Lm to study human listeriosis and in vivo host responses to this human pathogen.

  4. Varying constants, Gravitation and Cosmology

    CERN Document Server

    Uzan, Jean-Philippe

    2010-01-01

    Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describ...

  5. Time-Varying Fundamental Constants

    Science.gov (United States)

    Olive, Keith

    2003-04-01

    Recent data from quasar absorption systems can be interpreted as arising from a time variation in the fine-structure constant. However, there are numerous cosmological, astro-physical, and terrestrial bounds on any such variation. These includes bounds from Big Bang Nucleosynthesis (from the ^4He abundance), the Oklo reactor (from the resonant neutron capture cross-section of Sm), and from meteoretic lifetimes of heavy radioactive isotopes. The bounds on the variation of the fine-structure constant are significantly strengthened in models where all gauge and Yukawa couplings vary in a dependent manner, as would be expected in unified theories. Models which are consistent with all data are severly challenged when Equivalence Principle constraints are imposed.

  6. Varying Constants, Gravitation and Cosmology

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Uzan

    2011-03-01

    Full Text Available Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  7. Varying Constants, Gravitation and Cosmology.

    Science.gov (United States)

    Uzan, Jean-Philippe

    2011-01-01

    Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  8. Varying Constants, Gravitation and Cosmology

    Science.gov (United States)

    Uzan, Jean-Philippe

    2011-12-01

    Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  9. varying elastic parameters distributions

    KAUST Repository

    Moussawi, Ali

    2014-12-01

    The experimental identication of mechanical properties is crucial in mechanics for understanding material behavior and for the development of numerical models. Classical identi cation procedures employ standard shaped specimens, assume that the mechanical elds in the object are homogeneous, and recover global properties. Thus, multiple tests are required for full characterization of a heterogeneous object, leading to a time consuming and costly process. The development of non-contact, full- eld measurement techniques from which complex kinematic elds can be recorded has opened the door to a new way of thinking. From the identi cation point of view, suitable methods can be used to process these complex kinematic elds in order to recover multiple spatially varying parameters through one test or a few tests. The requirement is the development of identi cation techniques that can process these complex experimental data. This thesis introduces a novel identi cation technique called the constitutive compatibility method. The key idea is to de ne stresses as compatible with the observed kinematic eld through the chosen class of constitutive equation, making possible the uncoupling of the identi cation of stress from the identi cation of the material parameters. This uncoupling leads to parametrized solutions in cases where 5 the solution is non-unique (due to unknown traction boundary conditions) as demonstrated on 2D numerical examples. First the theory is outlined and the method is demonstrated in 2D applications. Second, the method is implemented within a domain decomposition framework in order to reduce the cost for processing very large problems. Finally, it is extended to 3D numerical examples. Promising results are shown for 2D and 3D problems.

  10. CD8+ TCR repertoire formation is guided primarily by the peptide component of the antigenic complex.

    Science.gov (United States)

    Koning, Dan; Costa, Ana I; Hoof, Ilka; Miles, John J; Nanlohy, Nening M; Ladell, Kristin; Matthews, Katherine K; Venturi, Vanessa; Schellens, Ingrid M M; Borghans, Jose A M; Kesmir, Can; Price, David A; van Baarle, Debbie

    2013-02-01

    CD8(+) T cells recognize infected or dysregulated cells via the clonotypically expressed αβ TCR, which engages Ag in the form of peptide bound to MHC class I (MHC I) on the target cell surface. Previous studies have indicated that a diverse Ag-specific TCR repertoire can be beneficial to the host, yet the determinants of clonotypic diversity are poorly defined. To better understand the factors that govern TCR repertoire formation, we conducted a comprehensive clonotypic analysis of CD8(+) T cell populations directed against epitopes derived from EBV and CMV. Neither pathogen source nor the restricting MHC I molecule were linked with TCR diversity; indeed, both HLA-A and HLA-B molecules were observed to interact with an overlapping repertoire of expressed TRBV genes. Peptide specificity, however, markedly impacted TCR diversity. In addition, distinct peptides sharing HLA restriction and viral origin mobilized TCR repertoires with distinct patterns of TRBV gene usage. Notably, no relationship was observed between immunodominance and TCR diversity. These findings provide new insights into the forces that shape the Ag-specific TCR repertoire in vivo and highlight a determinative role for the peptide component of the peptide-MHC I complex on the molecular frontline of CD8(+) T cell-mediated immune surveillance.

  11. Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination.

    Science.gov (United States)

    Qi, Qian; Cavanagh, Mary M; Le Saux, Sabine; NamKoong, Hong; Kim, Chulwoo; Turgano, Emerson; Liu, Yi; Wang, Chen; Mackey, Sally; Swan, Gary E; Dekker, Cornelia L; Olshen, Richard A; Boyd, Scott D; Weyand, Cornelia M; Tian, Lu; Goronzy, Jörg J

    2016-03-30

    Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood can escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-reactive CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. Although all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly. A genetic influence was seen for the sharing of individual TCR sequences from antigen-reactive cells but not for repertoire richness or the selection of dominant clones. VZV vaccination favored the expansion of infrequent VZV antigen-reactive TCRs, including those from naïve T cells with lesser boosting of dominant T cell clones. Thus, vaccination does not reinforce the in vivo selection that occurred during chronic infection but leads to a diversification of the VZV-reactive T cell repertoire. However, a single-booster immunization seems insufficient to establish new clonal dominance. Our results suggest that repertoire analysis of antigen-specific TCRs can be an important readout to assess whether a vaccination was able to generate memory cells in clonal sizes that are necessary for immune protection.

  12. Identification of a Bitter-Taste Receptor Gene Repertoire in Different Lagomorphs Species

    Science.gov (United States)

    Ferreira, Ana M.; Marques, Andreia T.; Fontanesi, Luca; Thulin, Carl-Gustaf; Sales-Baptista, Elvira; Araújo, Susana S.; Almeida, André M.

    2016-01-01

    The repertoires of bitter-taste receptor (T2R) gene have been described for several animal species, but these data are still scarce for Lagomorphs. The aim of the present work is to identify potential repertoires of T2R in several Lagomorph species, covering a wide geographical distribution. We studied these genes in Lepus timidus, L. europaeus, Oryctolagus cuniculus algirus, Romerolagus diazi, and Sylvilagus floridanus, using O. cuniculus cuniculus as control species for PCR and DNA sequencing. We studied the identities of the DNA sequences and built the corresponding phylogenetic tree. Sequencing was successful for both subspecies of O. cuniculus for all T2R genes studied, for five genes in Lepus, and for three genes in R. diazi and S. floridanus. We describe for the first time the partial repertoires of T2R genes for Lagomorphs species, other than the common rabbit. Our phylogenetic analyses indicate that sequence proximity levels follow the established taxonomic classification. PMID:27092177

  13. The Hmong Cultural Repertoire: Explaining Cultural Variation Within an Ethnic Group

    Directory of Open Access Journals (Sweden)

    Jeremy Hein

    1997-01-01

    Full Text Available Data on 382 Hmong in Laos and the United States reveal threetypes of cultural expertise: performing spiritual-medicalhealing; conducting life cycle rituals; and creating arts andcrafts. Only 31 percent of this sample engage in one or moreof the practices in this cultural repertoire. A mere 10percent of the sample account for 54 percent of the 247cultural practices. This pattern reveals the paradoxicalrelationship between ethnicity and culture. While all ethnicgroups have a culture, there is considerable variation amongmembers in their use of the group's cultural repertoire. Thispaper uses regression analysis to explain why some Hmong havemore cultural practices than others. The results suggest thatmales have greater access to the Hmong cultural repertoiredue their positions of authority in Laos, but that maternalcultural practices promote use of the repertoire by theirchildren regardless of leadership status.

  14. The peripheral CD8 T cell repertoire is largely independent of the presence of intestinal flora.

    Science.gov (United States)

    Bousso, P; Lemaître, F; Laouini, D; Kanellopoulos, J; Kourilsky, P

    2000-04-01

    While numerous studies have analyzed the shaping of T cell repertoires by self or foreign peptides, little is known on the influence of commensal self peptides derived from the intestinal flora (IF). Here, we have analyzed naive and immune repertoires in mice devoid of IF [germ-free (GF) mice]. First, by means of an extensive CDR3beta sequencing strategy, we show that the naive peripheral CD8 T cell repertoire does not exhibit a major imprint of IF antigens. Second, using MHC-peptide tetramers, CDR3beta length distribution analyses and TCR sequencing, we show that cytotoxic T lymphocyte (CTL) responses specific for two distinct epitopes are quasi-identical in normal and GF mice. Our findings indicate that, in general, peptides derived from the intestinal microflora have little if any influence on CTL responses in the mouse.

  15. Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis

    Directory of Open Access Journals (Sweden)

    Kazutaka Kitaura

    2017-05-01

    Full Text Available A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM. Class-switch recombination (CSR produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V, junctional (J sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

  16. Extending Thymidine Kinase Activity to the Catalytic Repertoire of Human Deoxycytidine Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Hazra, Saugata; Sabini, Eliszbetta; Ort, Stephan; Konrad, Manfred; Lavie, Arnon; (UIC); (MXPL-G)

    2009-03-04

    Salvage of nucleosides in the cytosol of human cells is carried out by deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1). Whereas TK1 is only responsible for thymidine phosphorylation, dCK is capable of converting dC, dA, and dG into their monophosphate forms. Using structural data on dCK, we predicted that select mutations at the active site would, in addition to making the enzyme faster, expand the catalytic repertoire of dCK to include thymidine. Specifically, we hypothesized that steric repulsion between the methyl group of the thymine base and Arg104 is the main factor preventing the phosphorylation of thymidine by wild-type dCK. Here we present kinetic data on several dCK variants where Arg104 has been replaced by select residues, all performed in combination with the mutation of Asp133 to an alanine. We show that several hydrophobic residues at position 104 endow dCK with thymidine kinase activity. Depending on the exact nature of the mutations, the enzyme's substrate preference is modified. The R104M-D133A double mutant is a pyrimidine-specific enzyme due to large K{sub m} values with purines. The crystal structure of the double mutant R104M-D133A in complex with the L-form of thymidine supplies a structural explanation for the ability of this variant to phosphorylate thymidine and thymidine analogs. The replacement of Arg104 by a smaller residue allows L-dT to bind deeper into the active site, making space for the C5-methyl group of the thymine base. The unique catalytic properties of several of the mutants make them good candidates for suicide-gene/protein-therapy applications.

  17. An ethogram of the common marmoset (Calithrix jacchus jacchus): general behavioural repertoire.

    Science.gov (United States)

    Stevenson, M F; Poole, T B

    1976-05-01

    The behavioural repertoire of four captive breeding pairs of Callithrix jacchus jacchus is described. Social communication took the form of postures, facial expressions, vocalizations and piloerection displays. Detailed analyses were made of piloerection displays, adult play, copulatory, aggressive, and prey-catching behaviour. Aggressive behaviour was uncommon in adult mated pairs. Play between adults showed a degree of temporal of temporal organization. Vocalizations were the main methods of intragroup communication whilst piloerection displays were directed towards members of other groups and also to unfamiliar objects. The behavioural repertoire of C. jacchus jacchus is compared with that of other Primates.

  18. Functioning of the mitochondrial ATP-dependent potassium channel in rats varying in their resistance to hypoxia. Involvement of the channel in the process of animal's adaptation to hypoxia.

    Science.gov (United States)

    Mironova, Galina D; Shigaeva, Maria I; Gritsenko, Elena N; Murzaeva, Svetlana V; Gorbacheva, Olga S; Germanova, Elena L; Lukyanova, Ludmila D

    2010-12-01

    The mechanism of tissue protection from ischemic damage by activation of the mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) remains unexplored. In this work, we have measured, using various approaches, the ATP-dependent mitochondrial K(+) transport in rats that differed in their resistance to hypoxia. The transport was found to be faster in the hypoxia-resistant rats as compared to that in the hypoxia-sensitive animals. Adaptation of animals to the intermittent normobaric hypoxia increased the rate of transport. At the same time, the intramitochondrial concentration of K(+) in the hypoxia-sensitive rats was higher than that in the resistant and adapted animals. This indicates that adaptation to hypoxia stimulates not only the influx of potassium into mitochondria, but also K(+)/H(+) exchange. When mitoK(ATP) was blocked, the rate of the mitochondrial H(2)O(2) production was found to be significantly higher in the hypoxia-resistant rats than that in the hypoxia-sensitive animals. The natural flavonoid-containing adaptogen Extralife, which has an evident antihypoxic effect, increased the rate of the mitochondrial ATP-dependent K(+) transport in vitro and increased the in vivo tolerance of hypoxia-sensitive rats to acute hypoxia 5-fold. The involvement of the mitochondrial K(+) transport in the mechanism of cell adaptation to hypoxia is discussed.

  19. Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution

    Directory of Open Access Journals (Sweden)

    Sercarz Eli E

    2011-07-01

    Full Text Available Abstract Background Non Obese Diabetic mice lacking B cells (NOD.Igμnull mice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor (TCR V beta repertoire of NOD.Igμnull mice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Igμnull mice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11 and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20. These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnull mice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulation in vitro. Conclusions Diabetes in NOD.Igμnull mice appears to be caused by a polyclonal repertoire of T cell

  20. Delay-dependent Conditions for Absolute Stability of Lurie Control Systems with Time-varying Delay%具有时变时滞的Lurie系统绝对稳定性的时滞相关条件

    Institute of Scientific and Technical Information of China (English)

    何勇; 吴敏

    2005-01-01

    Some delay-dependent absolute stability criteria for Lurie control systems with timevarying delay are derived, in which some free-weighting matrices are used to express the relationships between the terms in the Leibniz-Newton formula. These criteria are based on linear matrix inequality(LMI) such that the upper bound of time-delay guaranteeing the absolute stability and the free-weighting matrices can be obtained through the solutions of the LMI. Moreover, the Lyapunov functional constructed by the solutions of these LMIs is adopted to guarantee the absolute stability of the systems. Finally, some examples axe provided to demonstrate the effectiveness of the proposed methods.

  1. Ontogeny of the avian intestinal immunoglobulin repertoire: modification in CDR3 length and conserved VH-pseudogene usage.

    Science.gov (United States)

    den Hartog, Gerco; Crooijmans, Richard P M A; Parmentier, Henk K; Savelkoul, Huub F J; Bos, Nicolaas A; Lammers, Aart

    2013-12-01

    Immunoglobulins play an important role in maintenance of mucosal homeostasis in the gut. The antigen binding specificity of these immunoglobulins depends for a large part on the hypervariable CDR3 region. To gain knowledge about isotype-specific development of the CDR3 repertoire we examined CDR3 spectratypes at multiple time points between 4 and 70 days post hatch. In order to identify clonal expansions deviation from the normal distribution (SS) and the average CDR3 length was calculated. IgA-CDR3 regions were studied in more detail by DNA sequence analysis at day 7 and 70 and preferential VH pseudogene usage was estimated. The SS of CDR3 repertoires of the IgM, IgG and IgA isotypes successively increased, but for each isotype this increase was transiently. The length of the CDR3 regions decreased with age for IgM becoming similar to the CDR3 length of IgA at day 70. The IgA- and IgG-CDR3 lengths did not change with age. On average, the CDR3 length of IgA was the shortest. IgA CDR3 sequences were similar between animals aged 7 and 70 days. A limited number of pseudogenes was used, and no differences in pseudogene usage were observed between animals aged 7 and 70 days. Of the identified VH pseudogenes, half of the sequences used VH15, whilst a number of the pseudogenes were not used at all. We conclude that CDR3 spectratype profiles change during aging, whilst at the CDR3-sequence level, variation in VH pseudogene usage for ileal IgA is limited suggesting conservation during ontogeny.

  2. Interpretive Repertoires as Mirrors on Society and as Tools for Action: Reflections on Zeyer and Roth's "A Mirror of Society"

    Science.gov (United States)

    Milne, Catherine

    2009-01-01

    I respond to Zeyer and Roth's ("Cultural Studies of Science Education," 2009) paper on their use of interpretive repertoire analysis to explicate Swiss middle school students' dialogic responses to environmental issues. I focus on the strategy of interpretive repertoire analysis, making sense of the stance Zeyer and Roth take with this analysis by…

  3. Emotional Intelligence and the Conflict Resolution Repertoire of Couples in Tertiary Institutions in Imo State

    Science.gov (United States)

    Nnodum, B. I.; Ugwuegbulam, C. N.; Agbaenyi, I. G.

    2016-01-01

    This study is a descriptive survey that investigated the relationship between emotional intelligence and conflict resolution repertoire of couples in tertiary institutions. A sample of 250 married people were drawn from the population of couples in tertiary institutions in Imo State. Two researcher made and validated instruments were used in…

  4. Code-Mixing, Style Repertoire, and Language Variation: English in Hindi Poetic Creativity.

    Science.gov (United States)

    Kachru, Yamuna

    1989-01-01

    Discusses the style repertoire in the context of Hindi literature, the functions of code mixing varieties in Hindi literary works, and the implications for sociolinguistics of such investigations from linguistic and stylistic perspectives. Hindi poetry from the last three decades is examined to determine the effects of language mixing involving…

  5. SMRT sequencing provides insight into the diversity of the bovine immunoglobulin heavy chain repertoire

    Science.gov (United States)

    The vertebrate immune system produces a diverse antibody repertoire capable of responding to a vast array of antigens. This diversity is generated through a multifaceted process of gene segment recombination and somatic hypermutation or gene conversion. Recent advances in high-throughput sequencin...

  6. Insights into immune system development and function from mouse T-cell repertoires

    Science.gov (United States)

    Sethna, Zachary; Elhanati, Yuval; Dudgeon, Chrissy S.; Callan, Curtis G.; Levine, Arnold J.; Mora, Thierry; Walczak, Aleksandra M.

    2017-01-01

    The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult. We find a rapid increase with age in the number of random insertions and a dramatic increase in diversity. Because the blood accumulates thymic output over time, blood repertoires are mixtures of different statistical recombination processes, and we unravel the mixture statistics to obtain a picture of the time evolution of the early immune system. Sequence repertoire analysis also allows us to detect the statistical impact of selection on the output of the VDJ recombination process. The effects we find are nearly identical between thymus and blood, suggesting that our analysis mainly detects selection for proper folding of the TCR receptor protein. We further find that selection is weaker in laboratory mice than in humans and it does not affect the diversity of the repertoire. PMID:28196891

  7. Rat salivary gland reveals a more restricted IgA repertoire than ileum

    NARCIS (Netherlands)

    Stoel, Maaike; Evenhuis, Willem N. H.; Kroese, Frans G. M.; Bos, Nicolaas A.

    Secretory IgA is the most abundantly produced Ig in different mucosal tissues, such as the gastrointestinal tract and the salivary glands. These mucosal tissues are considered to be part of the common mucosal immune system. The specificity and immunoglobulin (19) V-H gene repertoire of the IgA

  8. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues.

    Science.gov (United States)

    Tabibian-Keissar, Hilla; Hazanov, Lena; Schiby, Ginette; Rosenthal, Noemie; Rakovsky, Aviya; Michaeli, Miri; Shahaf, Gitit Lavy; Pickman, Yishai; Rosenblatt, Kinneret; Melamed, Doron; Dunn-Walters, Deborah; Mehr, Ramit; Barshack, Iris

    2016-02-01

    The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 ± 7 years old, range 61-89) versus young (24 ± 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms.

  9. Interrogating the relationship between naïve and immune antiviral T cell repertoires.

    Science.gov (United States)

    La Gruta, Nicole L; Thomas, Paul G

    2013-08-01

    Understanding how naïve virus-specific CD8+ T cells influence the type of immune response generated after virus infection is critical for the development of enhanced therapeutic and vaccination strategies to exploit CD8+ T cell-mediated immunity. Recent technological advances in T cell isolation and T receptor sequencing have allowed for greater understanding of the basic structure of immune T cell repertoires, the diversity of responses within and between individuals, and changes in repertoires over time and in response to infection conditions. In this review, we discuss the current understanding of how T cell repertoires contribute to potent antiviral responses. Additionally we compare the state of the art in receptor sequencing, highlighting the advantages and disadvantages of the three most common approaches: next-generation sequencing, template-switch anchored RT-PCR, and multiplex single cell PCR. Finally, we describe how TCR sequencing has delineated the relationship between naïve and immune T cell repertoires.

  10. V beta T cell repertoire of CD8+ splenocytes selected on nonpolymorphic MHC class I molecules.

    Science.gov (United States)

    Laouini, D; Casrouge, A; Dalle, S; Lemonnier, F; Kourilsky, P; Kanellopoulos, J

    2000-12-01

    In this work, we have studied the role of the MHC class Ib molecules in the selection and maintenance of CD8(+) T splenocytes. We have compared the CD8(+) T cell repertoires of wild-type, H-2K-deficient, H-2D-deficient, or double knockout C57BL/6 mice. We show that the different CD8(+) repertoires, selected either by class Ia and class Ib or by class Ib molecules only, use the various V alpha (AV) and V beta (BV) rearrangements in the same proportion and without biases in the CDR3 size distribution. Furthermore, we have estimated the size of the BV repertoire in the four different strains of mice. Interestingly, we have found that the BV repertoire size is proportional to the overall number of CD8(+) splenocytes. This observation implies that BV diversity is positively correlated with the number of CD8(+) cells, even when the number of CD8(+) splenocytes is dramatically reduced (90% in the double knockout mice).

  11. Repertoires, Characters and Scenes: Sociolinguistic Difference in Turkish-German Comedy

    Science.gov (United States)

    Androutsopoulos, Jannis

    2012-01-01

    This paper examines representations of sociolinguistic difference in a German "ethnic comedy" as a means to contribute to a framework for the sociolinguistic study of film. Three levels of analysis of sociolinguistic difference in film are distinguished: repertoire analysis reconstructs the entirety of codes used in a film and their…

  12. Refining Learned Repertoire for Percussion Instruments in an Elementary Setting

    Science.gov (United States)

    Taylor, Donald M.

    2006-01-01

    The purpose of this study was to examine teaching effectiveness in an elementary music setting using student achievement as a dependent measure. Because Orff Schulwerk instruction is one of the most prevalent pedagogies in elementary music education, this study examined the rehearsal strategies of recognized Orff Schulwerk teachers as they worked…

  13. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires

    Directory of Open Access Journals (Sweden)

    Pemberton Trevor J

    2006-09-01

    Full Text Available Abstract Background The peptidyl-prolyl cis/trans isomerase (PPIase class of proteins is present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of three member families that share the ability to catalyze the cis/trans isomerisation of a prolyl bond. Some fungi have been used as model systems to investigate the role of PPIases within the cell, however how representative these repertoires are of other fungi or humans has not been fully investigated. Results PPIase numbers within these fungal repertoires appears associated with genome size and orthology between repertoires was found to be low. Phylogenetic analysis showed the single-domain FKBPs to evolve prior to the multi-domain FKBPs, whereas the multi-domain cyclophilins appear to evolve throughout cyclophilin evolution. A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. However, no such commonality was found with the FKBPs. Twelve of the 17 human cyclophilins and both human parvulins, but only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14 orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP. The repertoires of Cryptococcus neoformans, Aspergillus fumigatus, and Aspergillus nidulans were found to exhibit the highest orthology to the human repertoire, and Saccharomyces cerevisiae one of the lowest. Conclusion Given this data, we would hypothesize that: (i the evolution of the fungal PPIases is driven, at least in part, by the size of the proteome, (ii evolutionary pressures differ both between the different PPIase families and the different fungi, and (iii whilst the cyclophilins and parvulins have evolved to perform conserved

  14. IgM repertoire biodiversity is reduced in HIV-1 infection and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Li eYin

    2013-11-01

    Full Text Available Background: HIV-1 infection or systemic lupus erythematosus [SLE] disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 [CDRH3] sequence population level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations [SHM] in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly-neutralizing HIV-1 antibodies. Conclusions: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.

  15. Estimating the diversity, completeness, and cross-reactivity of the T cell repertoire

    Directory of Open Access Journals (Sweden)

    Veronika eZarnitsyna

    2013-12-01

    Full Text Available In order to recognize and combat a diverse array of pathogens the immune system has a large repertoire of T cells having unique T cell receptors (TCRs with only a few clones specific for any given antigen. We discuss how the number of different possible TCRs encoded in the genome (the potential repertoire and the number of different TCRs present in an individual (the realized repertoire can be measured. One puzzle is that the potential repertoire greatly exceeds the realized diversity of naive T cells within any individual. We show that the existing hypotheses fail to explain why the immune system has the potential to generate far more diversity than is used in an individual, and propose an alternative hypothesis of evolutionary sloppiness. Another immunological puzzle is why mice and humans have similar repertoires even though humans have over 1000 fold more T cells. We discuss how the idea of the protecton, the smallest unit of protection, might explain this discrepancy and estimate the size of protecton based on available precursor frequencies data. We then consider T cell cross-reactivity - the ability of a T cell clone to respond to more than one epitope. We extend existing calculations to estimate the extent of expected cross-reactivity between the responses to different pathogens. Our results are consistent with two observations: a low probability of observing cross-reactivity between the immune responses to two randomly chosen pathogens; and the ensemble of memory cells being sufficiently diverse to generate cross-reactive responses to new pathogens.

  16. A new high-throughput sequencing method for determining diversity and similarity of T cell receptor (TCR) α and β repertoires and identifying potential new invariant TCR α chains.

    Science.gov (United States)

    Kitaura, Kazutaka; Shini, Tadasu; Matsutani, Takaji; Suzuki, Ryuji

    2016-10-11

    High-throughput sequencing of T cell receptor (TCR) genes is a powerful tool for analyses of antigen specificity, clonality and diversity of T lymphocytes. Here, we developed a new TCR repertoire analysis method using 454 DNA sequencing technology in combination with an adaptor-ligation mediated polymerase chain reaction (PCR). This method allows the amplification of all TCR genes without PCR bias. To compare gene usage, diversity and similarity of expressed TCR repertoires among individuals, we conducted next-generation sequencing (NGS) of TRA and TRB genes in peripheral blood mononuclear cells from 20 healthy human individuals. From a total of 267,037 sequence reads from 20 individuals, 149,216 unique sequence reads were identified. Preferential usage of several V and J genes were observed while some recombinations of TRAV with TRAJ appeared to be restricted. The extent of TCR diversity was not significantly different between TRA and TRB, while TRA repertoires were more similar between individuals than TRB repertoires were. The interindividual similarity of TRA depended largely on the frequent presence of shared TCRs among two or more individuals. A publicly available TRA had a near-germline TCR with a shorter CDR3. Notably, shared TRA sequences, especially those shared among a large number of individuals', often contained TCRα related with invariant TCRα derived from invariant natural killer T cells and mucosal-associated invariant T cells. These results suggest that retrieval of shared TCRs by NGS would be useful for the identification of potential new invariant TCRα chains. This NGS method will enable the comprehensive quantitative analysis of TCR repertoires at a clonal level.

  17. Bouncing universes with varying constants

    Energy Technology Data Exchange (ETDEWEB)

    Barrow, John D [DAMTP, Centre for Mathematical Sciences, Cambridge University, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Kimberly, Dagny [Theoretical Physics, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BZ (United Kingdom); Magueijo, Joao [Theoretical Physics, Blackett Laboratory, Imperial College, Prince Consort Road, London SW7 2BZ (United Kingdom)

    2004-09-21

    We investigate the behaviour of exact closed bouncing Friedmann universes in theories with varying constants. We show that the simplest BSBM varying alpha theory leads to a bouncing universe. The value of alpha increases monotonically, remaining approximately constant during most of each cycle, but increasing significantly around each bounce. When dissipation is introduced we show that in each new cycle the universe expands for longer and to a larger size. We find a similar effect for closed bouncing universes in Brans-Dicke theory, where G also varies monotonically in time from cycle to cycle. Similar behaviour occurs also in varying speed of light theories.

  18. Bouncing Universes with Varying Constants

    CERN Document Server

    Barrow, J D; Magueijo, J; Barrow, John D.; Kimberly, Dagny; Magueijo, Joao

    2004-01-01

    We investigate the behaviour of exact closed bouncing Friedmann universes in theories with varying constants. We show that the simplest BSBM varying-alpha theory leads to a bouncing universe. The value of alpha increases monotonically, remaining approximately constant during most of each cycle, but increasing significantly around each bounce. When dissipation is introduced we show that in each new cycle the universe expands for longer and to a larger size. We find a similar effect for closed bouncing universes in Brans-Dicke theory, where $G$ also varies monotonically in time from cycle to cycle. Similar behaviour occurs also in varying speed of light theories.

  19. Song Repertoire and Origins of Crimean Population of Chiffchaff, Phylloscopus collybita (Sylviidae

    Directory of Open Access Journals (Sweden)

    Grishchenko A. V.

    2016-02-01

    Full Text Available Song repertoire of geographically isolated Chiffchaff population that formed in Crimean mountains in 1990s is analyzed. There are 42 song elements in the Crimean Chiffchaff repertoire. A quarter of their song elements appear to be specific for this population because it is absent in neighboring European Chiffchaff populations from regions to the north (Ph. c. abietinus subspecies and west (Ph. c. collybita subspecies. Comparison of song elements of Crimean Chiffchaffs with those of Caucasian birds of Ph. c. caucasica subspecies shows that they belong to same vocal population: specific elements in Crimean Chiffchaff songs are found also in songs of Caucasian birds. This is evidence that breeding population of Chiffchaff in Crimea originated from the species expansion from Caucasus, and that Crimean Chiffchaffs belong to Ph. c. caucasica subspecies.

  20. Finding meaning in first episode psychosis: experience, agency, and the cultural repertoire.

    Science.gov (United States)

    Larsen, John Aggergaard

    2004-12-01

    The article examines individuals' attempts to generate meaning following their experiences with psychosis. The inquiry is based on a person-centered ethnographic study of a Danish mental health community program for early intervention in schizophrenia and involves longitudinal interviews with 15 of its participants. The article takes an existential anthropological perspective emphasizing agency and cultural phenomenology to investigate how individuals draw on resources from the cultural repertoire to make sense of personally disturbing experiences during their psychosis. It is suggested that the concept of "system of explanation" has advantages over, for example, "illness narrative" and "explanatory model" when demonstrating how some individuals engage in the creative analytic and theory-building work of bricolage, selecting, adding, and combining various systems of explanation. Delusions are equally derived from the cultural repertoire but are constructed as dogmatic explanations that are idiosyncratic to the individual who holds them.

  1. High-throughput Sequencing Based Immune Repertoire Study during Infectious Disease

    Directory of Open Access Journals (Sweden)

    Dongni Hou

    2016-08-01

    Full Text Available The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases that achieved by traditional techniques and high-throughput sequencing techniques. High-throughput sequencing techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge, and also provides a basis for further development of novel diagnostic markers, immunotherapies and vaccines.

  2. Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires.

    Science.gov (United States)

    Burstein, David; Amaro, Francisco; Zusman, Tal; Lifshitz, Ziv; Cohen, Ofir; Gilbert, Jack A; Pupko, Tal; Shuman, Howard A; Segal, Gil

    2016-02-01

    Infection by the human pathogen Legionella pneumophila relies on the translocation of ∼ 300 virulence proteins, termed effectors, which manipulate host cell processes. However, almost no information exists regarding effectors in other Legionella pathogens. Here we sequenced, assembled and characterized the genomes of 38 Legionella species and predicted their effector repertoires using a previously validated machine learning approach. This analysis identified 5,885 predicted effectors. The effector repertoires of different Legionella species were found to be largely non-overlapping, and only seven core effectors were shared by all species studied. Species-specific effectors had atypically low GC content, suggesting exogenous acquisition, possibly from the natural protozoan hosts of these species. Furthermore, we detected numerous new conserved effector domains and discovered new domain combinations, which allowed the inference of as yet undescribed effector functions. The effector collection and network of domain architectures described here can serve as a roadmap for future studies of effector function and evolution.

  3. Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire.

    Science.gov (United States)

    Roy, Edwige; Togbe, Dieudonnée; Holdorf, Amy D; Trubetskoy, Dmitry; Nabti, Sabrina; Küblbeck, Günter; Klevenz, Alexandra; Kopp-Schneider, Annette; Leithäuser, Frank; Möller, Peter; Bladt, Friedhelm; Hämmerling, Günter; Arnold, Bernd; Pawson, Tony; Tafuri, Anna

    2010-08-31

    The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability.

  4. Quantitative Analysis of Repertoire Scale Immunoglobulin properties in Vaccine Induced B cell Responses

    Science.gov (United States)

    2017-08-14

    however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal...undergone further rounds of affinity maturation. Interestingly, despite their similar genetic backgrounds, eVLP-vaccinated mice showed little overlap...ReFeRenceS 1. Cobey S, Wilson P, Matsen FA. The evolution within us. Philos Trans R Soc Lond B Biol Sci (2015) 370(1676):20140235. doi:10.1098/rstb

  5. Contrasted evolution of the vomeronasal receptor repertoires in mammals and squamate reptiles.

    Science.gov (United States)

    Brykczynska, Urszula; Tzika, Athanasia C; Rodriguez, Ivan; Milinkovitch, Michel C

    2013-01-01

    The vomeronasal organ (VNO) is an olfactory structure that detects pheromones and environmental cues. It consists of sensory neurons that express evolutionary unrelated groups of transmembrane chemoreceptors. The predominant V1R and V2R receptor repertoires are believed to detect airborne and water-soluble molecules, respectively. It has been suggested that the shift in habitat of early tetrapods from water to land is reflected by an increase in the ratio of V1R/V2R genes. Snakes, which have a very large VNO associated with a sophisticated tongue delivery system, are missing from this analysis. Here, we use RNA-seq and RNA in situ hybridization to study the diversity, evolution, and expression pattern of the corn snake vomeronasal receptor repertoires. Our analyses indicate that snakes and lizards retain an extremely limited number of V1R genes but exhibit a large number of V2R genes, including multiple lineages of reptile-specific and snake-specific expansions. We finally show that the peculiar bigenic pattern of V2R vomeronasal receptor gene transcription observed in mammals is conserved in squamate reptiles, hinting at an important but unknown functional role played by this expression strategy. Our results do not support the hypothesis that the shift to a vomeronasal receptor repertoire dominated by V1Rs in mammals reflects the evolutionary transition of early tetrapods from water to land. This study sheds light on the evolutionary dynamics of the vomeronasal receptor families in vertebrates and reveals how mammals and squamates differentially adapted the same ancestral vomeronasal repertoire to succeed in a terrestrial environment.

  6. Repertoire of the acoustic communication of the azure jay Cyanocorax caeruleus (Vieillot) (Aves, Corvidae)

    OpenAIRE

    Luiz dos Anjos; Vielliard, Jacques M.E.

    1993-01-01

    The vocal repertoire of the Azure Jay Cyanocorax caeruleus (Vieillot, 1818) is approached from a quali-quantitative point of view. The qualitative analysis was carried out both in the field and in captivity: the quantitative analysis was made only in captivity. Social acoustic communication in the Azure Jay is achieved through the use of two types of call: basic and intermediate calls. Fourteen basic calls are identified and presented through sonograms: the sotto voce song (courtship call) is...

  7. Changes in the repertoire of natural antibodies caused by immunization with bacterial antigens

    DEFF Research Database (Denmark)

    Shilova, N V; Navakouski, M J; Huflejt, M

    2011-01-01

    The repertoire of natural anti-glycan antibodies in naïve chickens and in chickens immunized with bacteria Burkholderia mallei, Burkholderia pseudomallei, and Francisella tularensis as well as with peptides from an outer membrane protein of B. pseudomallei was studied. A relatively restricted...... pattern of natural antibodies (first of all IgY against bacterial cell wall peptidoglycan fragments, L-Rha, and core N-acetyllactosamine) shrank and, moreover, the level of detectable antibodies decreased as a result of immunization....

  8. Cultural repertoires and food-related household technology within colonia households under conditions of material hardship

    OpenAIRE

    Dean Wesley R; Sharkey Joseph R; Johnson Cassandra M; John Julie

    2012-01-01

    Abstract Introduction Mexican-origin women in the U.S. living in colonias (new-destination Mexican-immigrant communities) along the Texas-Mexico border suffer from a high incidence of food insecurity and diet-related chronic disease. Understanding environmental factors that influence food-related behaviors among this population will be important to improving the well-being of colonia households. This article focuses on cultural repertoires that enable food choice and the everyday uses of tech...

  9. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Science.gov (United States)

    Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo; Pagnani, Andrea

    2016-04-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models.

  10. Practical compassions: repertoires of practice and compassion talk in acute mental healthcare.

    Science.gov (United States)

    Brown, Brian; Crawford, Paul; Gilbert, Paul; Gilbert, Jean; Gale, Corinne

    2014-03-01

    This article reports an exploratory study of the concept of compassion in the work of 20 mental health practitioners in a UK Midlands facility. Using notions of practice derived from phenomenology and Bourdieusian sociology and notions of emotional labour we identify two contrasting interpretive repertoires in discussions of compassion. The first, the practical compassion repertoire, evokes the practical, physical and bodily aspects of compassion. It involves organising being with patients, playing games, anticipating disruption and taking them outside for cigarettes. Practitioners described being aware that these practical, bodily activities could lead to patients 'opening up', disclosing their interior concerns and enabling practical, compassionate mental health work to take place. In contrast, the second, organisational repertoire, concerns organisational constraints on compassionate practice. The shortage of staff, the record-keeping and internal processes of quality control were seen as time-greedy and apt to detract from contact with patients. The findings are discussed in relation to Bourdieu and Merleau-Ponty's phenomenological accounts of practice and habit and set in context in the growing interest in placing compassion centrally in healthcare. We also explore how the exercise of compassion in the way our participants describe it can afford the more effective exercise of medical power.

  11. Immunoglobulin gene repertoire diversification and selection in the stomach – from gastritis to gastric lymphomas

    Directory of Open Access Journals (Sweden)

    Miri eMichaeli

    2014-06-01

    Full Text Available Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis with H. pylori background can cause gastric mucosa-associated lymphoid tissue lymphoma (MALT-L, which sometimes further transforms into diffuse large B cell lymphoma (DLBCL. However, gastric DLBCL can also be initiated de novo. The mechanisms underlying transformation into DLBCL are not completely understood. We analyzed immunoglobulin repertoires and clonal trees to investigate whether and how immunoglobulin gene repertoires, clonal diversification and selection in gastritis, gastric MALT-L and DLBCL differ from each other and from normal responses. The two gastritis types (positive or negative for H. pylori had similarly diverse repertoires. MALT-L dominant clones presented higher diversification and longer mutational histories compared with all other conditions. DLBCL dominant clones displayed lower clonal diversification, suggesting the transforming events are triggered by similar responses in different patients. These results are surprising, as we expected to find similarities between the dominant clones of gastritis and MALT-L and between those of MALT-L and DLBCL.

  12. Reductive evolution of architectural repertoires in proteomes and the birth of the tripartite world.

    Science.gov (United States)

    Wang, Minglei; Yafremava, Liudmila S; Caetano-Anollés, Derek; Mittenthal, Jay E; Caetano-Anollés, Gustavo

    2007-11-01

    The repertoire of protein architectures in proteomes is evolutionarily conserved and capable of preserving an accurate record of genomic history. Here we use a census of protein architecture in 185 genomes that have been fully sequenced to generate genome-based phylogenies that describe the evolution of the protein world at fold (F) and fold superfamily (FSF) levels. The patterns of representation of F and FSF architectures over evolutionary history suggest three epochs in the evolution of the protein world: (1) architectural diversification, where members of an architecturally rich ancestral community diversified their protein repertoire; (2) superkingdom specification, where superkingdoms Archaea, Bacteria, and Eukarya were specified; and (3) organismal diversification, where F and FSF specific to relatively small sets of organisms appeared as the result of diversification of organismal lineages. Functional annotation of FSF along these architectural chronologies revealed patterns of discovery of biological function. Most importantly, the analysis identified an early and extensive differential loss of architectures occurring primarily in Archaea that segregates the archaeal lineage from the ancient community of organisms and establishes the first organismal divide. Reconstruction of phylogenomic trees of proteomes reflects the timeline of architectural diversification in the emerging lineages. Thus, Archaea undertook a minimalist strategy using only a small subset of the full architectural repertoire and then crystallized into a diversified superkingdom late in evolution. Our analysis also suggests a communal ancestor to all life that was molecularly complex and adopted genomic strategies currently present in Eukarya.

  13. Dance choreography is coordinated with song repertoire in a complex avian display.

    Science.gov (United States)

    Dalziell, Anastasia H; Peters, Richard A; Cockburn, Andrew; Dorland, Alexandra D; Maisey, Alex C; Magrath, Robert D

    2013-06-17

    All human cultures have music and dance, and the two activities are so closely integrated that many languages use just one word to describe both. Recent research points to a deep cognitive connection between music and dance-like movements in humans, fueling speculation that music and dance have coevolved and prompting the need for studies of audiovisual displays in other animals. However, little is known about how nonhuman animals integrate acoustic and movement display components. One striking property of human displays is that performers coordinate dance with music by matching types of dance movements with types of music, as when dancers waltz to waltz music. Here, we show that a bird also temporally coordinates a repertoire of song types with a repertoire of dance-like movements. During displays, male superb lyrebirds (Menura novaehollandiae) sing four different song types, matching each with a unique set of movements and delivering song and dance types in a predictable sequence. Crucially, display movements are both unnecessary for the production of sound and voluntary, because males sometimes sing without dancing. Thus, the coordination of independently produced repertoires of acoustic and movement signals is not a uniquely human trait.

  14. Repertoire of the acoustic communication of the azure jay Cyanocorax caeruleus (Vieillot (Aves, Corvidae

    Directory of Open Access Journals (Sweden)

    Luiz dos Anjos

    1993-01-01

    Full Text Available The vocal repertoire of the Azure Jay Cyanocorax caeruleus (Vieillot, 1818 is approached from a quali-quantitative point of view. The qualitative analysis was carried out both in the field and in captivity: the quantitative analysis was made only in captivity. Social acoustic communication in the Azure Jay is achieved through the use of two types of call: basic and intermediate calls. Fourteen basic calls are identified and presented through sonograms: the sotto voce song (courtship call is related only to courtship and the social call is interpreted as the song in the Azure Jay. The intermediate calls are recombinations of the basic calls uttered during an alteration in motivation level. Examples of them are presented through sonograms of vocalizations recorded during mobbing predators and intraspecific agonistic contexts. The social, social-alarm, contact, flight, proximity, threat and social identity calls were those most frequently uttered by daylight: the other calls represented around 15% of the total number of utterances. The hypothesis of the evolution in American Jays, which tends to simplification of vocal repertoire (HARDY, 1961; 1969, is analysed; C. caeruleus seems to have a small actively-used repertoire.

  15. Ibrutinib Therapy Increases T Cell Repertoire Diversity in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Yin, Qingsong; Sivina, Mariela; Robins, Harlan; Yusko, Erik; Vignali, Marissa; O'Brien, Susan; Keating, Michael J; Ferrajoli, Alessandra; Estrov, Zeev; Jain, Nitin; Wierda, William G; Burger, Jan A

    2017-02-15

    The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy. We noted elevated CD4(+) and CD8(+) T cell numbers and a restricted TCRβ repertoire in all pretreatment samples. After 1 y of ibrutinib therapy, elevated peripheral blood T cell numbers and T cell-related cytokine levels had normalized, and T cell repertoire diversity increased significantly. Dominant TCRβ clones in pretreatment samples declined or became undetectable, and the number of productive unique clones increased significantly during ibrutinib therapy, with the emergence of large numbers of low-frequency TCRβ clones. Importantly, broader TCR repertoire diversity was associated with clinical efficacy and lower rates of infections during ibrutinib therapy. These data demonstrate that ibrutinib therapy increases diversification of the T cell compartment in CLL patients, which contributes to cellular immune reconstitution.

  16. Interpretative Repertoires of Multiculturalism – Supporting and Challenging Hierarchical Intergroup Relations

    Directory of Open Access Journals (Sweden)

    Emma Nortio

    2016-11-01

    Full Text Available Social psychological research on immigrant integration has predominantly examined multiculturalism from the perspective of majority members, and has seen it to be in conflict with that of minority members. In this discursive psychological study, we analyzed how members of the Finnish majority and different immigrant groups discussed managing ethnic and cultural diversity. As a result, four different interpretative repertoires of multiculturalism were identified. The first two repertoires normalize the hierarchical relations between immgrants and hosts. The other two repertoires questioned and criticized multiculturalism as an official policy or as everyday practices that highlight the importance of ethnic and cultural group memberships and that enable the discriminatory and essentializing treatment of immigrants. Our analysis showed that both minority and majority members can make sense of and orient towards multiculturalism in many different ways and that, contrary to the common assumption based on previous research, the viewpoints presented are not always clearly divided between the groups. Finally, implications of the results for multiculturalism as an ideology and as practices are discussed.

  17. The Giardia lamblia vsp gene repertoire: characteristics, genomic organization, and evolution

    Directory of Open Access Journals (Sweden)

    Nash Theodore E

    2010-07-01

    Full Text Available Abstract Background Giardia lamblia trophozoites colonize the intestines of susceptible mammals and cause diarrhea, which can be prolonged despite an intestinal immune response. The variable expression of the variant-specific surface protein (VSP genes may contribute to this prolonged infection. Only one is expressed at a time, and switching expression from one gene to another occurs by an epigenetic mechanism. Results The WB Giardia isolate has been sequenced at 10× coverage and assembled into 306 contigs as large as 870 kb in size. We have used this assembly to evaluate the genomic organization and evolution of the vsp repertoire. We have identified 228 complete and 75 partial vsp gene sequences for an estimated repertoire of 270 to 303, making up about 4% of the genome. The vsp gene diversity includes 30 genes containing tandem repeats, and 14 vsp pairs of identical genes present in either head to head or tail to tail configurations (designated as inverted pairs, where the two genes are separated by 2 to 4 kb of non-coding DNA. Interestingly, over half the total vsp repertoire is present in the form of linear gene arrays that can contain up to 10 vsp gene members. Lastly, evidence for recombination within and across minor clades of vsp genes is provided. Conclusions The data we present here is the first comprehensive analysis of the vsp gene family from the Genotype A1 WB isolate with an emphasis on vsp characterization, function, evolution and contributions to pathogenesis of this important pathogen.

  18. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Directory of Open Access Journals (Sweden)

    Lorenzo Asti

    2016-04-01

    Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

  19. Varying c and Particle Horizons

    CERN Document Server

    Chimento, L P; Pavón, D; Chimento, Luis P; Jakubi, Alejandro S; Pavon, Diego

    2001-01-01

    We explore what restrictions may impose the second law of thermodynamics on varying speed of light theories. We find that the attractor scenario solving the flatness problem is consistent with the generalized second law at late time.

  20. Characterization of human αβTCR repertoire and discovery of D-D fusion in TCRβ chains.

    Science.gov (United States)

    Liu, Peipei; Liu, Di; Yang, Xi; Gao, Jing; Chen, Yan; Xiao, Xue; Liu, Fei; Zou, Jing; Wu, Jun; Ma, Juncai; Zhao, Fangqing; Zhou, Xuyu; Gao, George F; Zhu, Baoli

    2014-01-01

    The characterization of the human T-cell receptor (TCR) repertoire has made remarkable progress, with most of the work focusing on the TCRβ chains. Here, we analyzed the diversity and complexity of both the TCRα and TCRβ repertoires of three healthy donors. We found that the diversity of the TCRα repertoire is higher than that of the TCRβ repertoire, whereas the usages of the V and J genes tended to be preferential with similar TRAV and TRAJ patterns in all three donors. The V-J pairings, like the V and J gene usages, were slightly preferential. We also found that the TRDV1 gene rearranges with the majority of TRAJ genes, suggesting that TRDV1 is a shared TRAV/DV gene (TRAV42/DV1). Moreover, we uncovered the presence of tandem TRBD (TRB D gene) usage in ~2% of the productive human TCRβ CDR3 sequences.

  1. Highly diverse TCRα chain repertoire of pre-immune CD8+ T cells reveals new insights in gene recombination

    Science.gov (United States)

    Genolet, Raphael; Stevenson, Brian J; Farinelli, Laurent; Østerås, Magne; Luescher, Immanuel F

    2012-01-01

    Although the T-cell receptor αδ (TCRαδ) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCRα chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By sequencing tens of millions of TCRα chain transcripts from naive mouse CD8+ T cells, we observed a hugely diverse repertoire, comprising nearly all possible TRAV-TRAJ combinations. Our findings are not compatible with sequential coordinate gene recombination, but rather with a model in which contraction and DNA looping in the TCRαδ locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCRα chain repertoire necessitates deletion of failed attempts by thymic-positive selection and is essential for the formation of highly diverse TCRαβ repertoires, capable of providing good protective immunity. PMID:22373576

  2. Encoding of situations in the vocal repertoire of piglets (Sus scrofa): a comparison of discrete and graded classifications

    National Research Council Canada - National Science Library

    Tallet, Céline; Linhart, Pavel; Policht, Richard; Hammerschmidt, Kurt; Šimeček, Petr; Kratinova, Petra; Špinka, Marek

    2013-01-01

    .... The division of the vocal repertoire of piglets into two call types has previously been used in many experimental studies into pig acoustic communication and the five call types correspond well...

  3. Vocal repertoire of the New Zealand kea parrot Nestor notabilis

    Institute of Scientific and Technical Information of China (English)

    Raoul SCHWING; Stuart PARSONS; Ximena J.NELSON

    2012-01-01

    The unique alpine-living kea parrot Nestor notabilis has been the focus of numerous cognitive studies,but its communication system has so far been largely neglected.We examined 2,884 calls recorded in New Zealand's Southern Alps.Based on audio and visual spectrographic differences,these calls were categorised into seven distinct call types:the non-oscillating ‘screech' contact call and ‘mew'; and the oscillating ‘trill',‘chatter',‘warble' and ‘whistle'; and a hybrid ‘screech-trill'.Most of these calls contained aspects that were individually unique,in addition to potentially encoding for an individual's sex and age.Additionally,for each recording,the sender's previous and next calls were noted,as well as any response given by conspecifics.We found that the previous and next calls made by the sender were most often of the same type,and that the next most likely preceding and/or following call type was the screech call,a contact call which sounds like the 'kee-ah' from which the bird's name derives.As a social bird capable of covering large distances over visually obstructive terrain,long distance contact calls may be of considerable importance for social cohesion.Contact calls allow kea to locate conspecifics and congregate in temporary groups for social activities.The most likely response to any given call was a screech,usually followed by the same type of call as the initial call made by the sender,although responses differed depending on the age of the caller.The exception was the warble,the kea's play call,to which the most likely response was another warble.Being the most common call type,as well as the default response to another call,it appears that the ‘contagious' screech contact call plays a central role in kea vocal communication and social cohesion.

  4. Vocal repertoire of the New Zealand kea parrot Nestor notabilis

    Directory of Open Access Journals (Sweden)

    Raoul SCHWING, Stuart PARSONS, Ximena J. NELSON

    2012-10-01

    Full Text Available The unique alpine-living kea parrot Nestor notabilis has been the focus of numerous cognitive studies, but its communication system has so far been largely neglected. We examined 2,884 calls recorded in New Zealand’s Southern Alps. Based on audio and visual spectrographic differences, these calls were categorised into seven distinct call types: the non-oscillating ‘screech’ contact call and ‘mew’; and the oscillating ‘trill’, ‘chatter’, ‘warble’ and ‘whistle’; and a hybrid ‘screech-trill’. Most of these calls contained aspects that were individually unique, in addition to potentially encoding for an individual’s sex and age. Additionally, for each recording, the sender’s previous and next calls were noted, as well as any response given by conspecifics. We found that the previous and next calls made by the sender were most often of the same type, and that the next most likely preceding and/or following call type was the screech call, a contact call which sounds like the ‘kee-ah’ from which the bird’s name derives. As a social bird capable of covering large distances over visually obstructive terrain, long distance contact calls may be of considerable importance for social cohesion. Contact calls allow kea to locate conspecifics and congregate in temporary groups for social activities. The most likely response to any given call was a screech, usually followed by the same type of call as the initial call made by the sender, although responses differed depending on the age of the caller. The exception was the warble, the kea’s play call, to which the most likely response was another warble. Being the most common call type, as well as the default response to another call, it appears that the ‘contagious’ screech contact call plays a central role in kea vocal communication and social cohesion [Current Zoology 58 (5: 727-740, 2012].

  5. The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites

    OpenAIRE

    Schneider, Christoph; Smith, David F; Cummings, Richard D.; Boligan, Kayluz Frias; Hamilton, Robert G.; Bochner, Bruce S; Miescher, Sylvia; Simon, Hans-Uwe; Pashov, Anastas; Vassilev, Tchavdar; von Gunten, Stephan

    2015-01-01

    Despite the paradigm that carbohydrates are T cell-independent antigens, isotype-switched glycan-specific IgG antibodies and polysaccharide-specific T cells are found in humans. We employed a systems level approach combined with glycan array technology to decipher the repertoire of carbohydrate-specific IgG antibodies in intravenous and subcutaneous immunoglobulin (IVIG/SCIG) preparations. A strikingly universal architecture of this repertoire with modular organization among different donor p...

  6. Interpretive repertoires as mirrors on society and as tools for action: reflections on Zeyer and Roth's A mirror of society

    Science.gov (United States)

    Milne, Catherine

    2009-12-01

    I respond to Zeyer and Roth's (Cultural Studies of Science Education, 2009) paper on their use of interpretive repertoire analysis to explicate Swiss middle school students' dialogic responses to environmental issues. I focus on the strategy of interpretive repertoire analysis, making sense of the stance Zeyer and Roth take with this analysis by synthesizing their argument and comparing their analysis with other researchers that have also used this analytic tool. Interpretive repertoires are discourse resources, including mores, tropes, and metaphors that can be evoked by speakers in support of a tenuous claim. So interpretive repertoires have rhetorical character and function. Interpretive repertoire analysis requires looking for patterns in the contradictions in the speech of a collective of participants that can be codified as interpretive repertoires. Interpretive repertoires provide insight into macro-structures that frame, and are used to justify participants' behavior. My response to Zeyer and Roth's argument might also be thought to be contradictory but I think defensible. In this paper, I outline why I am excited by the possibilities I can image for this type of analysis in areas of science education research. However, I also felt the need to identify possible limitations of Zeyer and Roth's exclusive focus on environmental issues to the neglect of other issues, such as those associated with gender, embedded in participants' discourse. I argue that a critical and historical focus, in conjunction with interpretive repertoire analysis, offer a rich strategy for analysis in science education research, especially in the study of macrostructures, such as gender, race, identity and power.

  7. B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.

    Science.gov (United States)

    Beausang, John F; Fan, H Christina; Sit, Rene; Hutchins, Maria U; Jirage, Kshama; Curtis, Rachael; Hutchins, Edward; Quake, Stephen R; Yabu, Julie M

    2017-01-13

    Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative

  8. Design and validation of a synthetic VH repertoire with tailored diversity for protein recognition.

    Science.gov (United States)

    Almagro, Juan Carlos; Quintero-Hernández, Veronica; Ortiz-León, Mauricio; Velandia, Alvaro; Smith, Sylvia L; Becerril, Baltazar

    2006-01-01

    Previous studies have indicated differences in the specificity-determining residues (SDRs) of antibodies that recognize haptens, peptides, or proteins. Here, we designed a V(H) repertoire based on the human scaffold 3-23/J(H)4 and diversification of high and medium-usage SDRs of anti-protein and anti-peptide antibodies. The repertoire was synthesized by overlapping polymerase chain reaction (PCR) and combined with the V(L) chain of the anti-hen egg-white lysozyme (HEL) antibody D1.3. The resulting chimeric single-chain Fv fragments (scFvs) phage-displayed library was panned in HEL-coated immunotubes. After two rounds of selection under non-stringent conditions, that is, trypsinization after 2 h of incubation at room temperature, 63 of 167 clones analyzed (38%) were found to express scFvs specific to HEL. Twenty clones were characterized by DNA sequencing resulting in 10 unique scFvs. Interestingly, the panel of unique scFvs was highly diverse, with V(H) sequences differing in 16 of the 17 positions variegated in the repertoire. Thus, diverse chemico-physical and structural solutions were selected from the library, even when the V(H) repertoire was constrained by the V(L) chain of D1.3 to yield binders against a definite region of HEL surface. The more often selected scFvs, namely H6-1 and B7-1, which differed in eight SDRs, showed levels of expression in E. coli TG1 strain, 6 and 10 times higher than the parental D1.3 Fv fragment, respectively. Dissociation constants (K(Ds)) measured in the BIAcore were 11 and 6.6 nM for H6-1 and B7-1, respectively. These values compared well to the K(D) of 4.7 nM measured for D1.3, indicating that the V(H) repertoire here designed is a valuable source of diverse, well-expressed and high affinity V(H) domains.

  9. Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences

    Directory of Open Access Journals (Sweden)

    Jacob D. Galson

    2015-12-01

    Full Text Available Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

  10. In vitro methods for generating CD8+ T-cell clones for immunotherapy from the naïve repertoire.

    Science.gov (United States)

    Ho, William Y; Nguyen, Hieu N; Wolfl, Matthias; Kuball, Juergen; Greenberg, Philip D

    2006-03-20

    Innovations in gene discovery and the analysis of gene expression are facilitating the identification of a growing number of antigens that could potentially be targeted for immunotherapy of tumors. Methods to reliably generate antigen-specific T-cell responses in vitro would be useful not only to screen candidate antigens for immunogenicity prior to embarking on in vivo vaccination trials, but also to generate T-cell lines or clones that could be used directly for adoptive immunotherapy approaches. Although many techniques have proven successful for expanding ex vivo effector cells from antigen-specific memory CD8(+) cells that have been primed in vivo, methods to reliably generate high-avidity CTL clones from the naïve repertoire have not been well described. Various methods for the induction and expansion of antigen-specific CD8(+) CTL clones from healthy A2(+) donors were compared, using WT1 as a model tumor-associated antigen for which there is a low frequency of precursor T cells in naïve individuals. In contrast to the well-studied Melan-A/MART-1 (Melan-A) A2-restricted response, for which the CD8(+) T-cell precursor frequency in the naïve repertoire is unusually high, successful expansion of WT1-specific CD8(+) T cells appeared to be more dependent upon cell culture conditions. In particular, primary stimulation with autologous peptide-loaded monocyte-derived DC generated in 48 h (DC2d) was more effective in expanding WT1-reactive populations of CTL than stimulation with DC generated using the more standard week-long protocol (DC7d). Adding supplemental IL-7 2 to 3 days after initiation of a stimulation cycle expanded antigen-specific cells within CTL lines more efficiently than including the cytokine from the beginning of the cycle. Following primary stimulation with peptide-loaded mature DC, subsequent restimulation with peptide-loaded PBMC as the stimulators was more effective at expanding antigen-specific cells than repeated stimulation with mature DC

  11. The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

    Science.gov (United States)

    Collado, Javier A.; Guitart, Carolina; Ciudad, M. Teresa; Alvarez, Iñaki; Jaraquemada, Dolores

    2013-01-01

    T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions. PMID:24381570

  12. The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

    Science.gov (United States)

    Collado, Javier A; Guitart, Carolina; Ciudad, M Teresa; Alvarez, Iñaki; Jaraquemada, Dolores

    2013-12-17

    T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions.

  13. Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

    Directory of Open Access Journals (Sweden)

    Alonso Ángel

    2006-03-01

    Full Text Available Abstract Background Papillomaviruses (PVs infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR of the virus. It is believed that there is a core of transcription factor binding sites (TFBS common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses. Results We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS. Conclusion There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host, i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs.

  14. Smallest bitter taste receptor(T2Rs)gene repertoire in carnivores%Smallest bitter taste receptor (T2Rs) gene repertoire in carnivores

    Institute of Scientific and Technical Information of China (English)

    Ling-Ling HU; Peng SHI

    2013-01-01

    Bitter taste reception is presumably associated with dietary selection,preventing animals from ingesting potentially harmful compounds.Accordingly,carnivores,who encounter these toxic substances less often,should have fewer genes associated with bitter taste reception compared with herbivores and omnivores.To investigate the genetic basis of bitter taste reception,we confirmed bitter taste receptor (T2R) genes previously found in the genome sequences of two herbivores (cow and horse),two omnivores (mouse and rat) and one carnivore (dog).We also identified,for the first time,the T2R repertoire from the genome of other four carnivore species (ferret,giant panda,polar bear and cat) and detected 17-20 bitter receptor genes from the five carnivore genomes,including 12-16 intact genes,0-1 partial but putatively functional genes,and 3-8 pseudogenes.Both the intact T2R genes and the total T2R gene number among carnivores were the smallest among the tested species,supporting earlier speculations that carnivores have fewer T2R genes,herbivores an intermediate number,and omnivores the largest T2R gene repertoire.To further explain the genetic basis for this disparity,we constructed a phylogenetic tree,which showed most of the T2R genes from the five carnivores were one-to-one orthologs across the tree,suggesting that carnivore T2Rs were conserved among mammals.Similarly,the small carnivore T2R family size was likely due to rare duplication events.Collectively,these results strengthen arguments for the connection between T2R gene family size,diet and habit.

  15. Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid receptor target genes in mouse embryonic fibroblasts.

    Science.gov (United States)

    Al Tanoury, Ziad; Piskunov, Aleksandr; Andriamoratsiresy, Dina; Gaouar, Samia; Lutzing, Régis; Ye, Tao; Jost, Bernard; Keime, Céline; Rochette-Egly, Cécile

    2014-02-01

    Nuclear retinoic acid (RA) receptors (RARα, β and γ) are ligand-dependent transcription factors that regulate the expression of a battery of genes involved in cell differentiation and proliferation. They are also phosphoproteins and we previously showed the importance of their phosphorylation in their transcriptional activity. In the study reported here, we conducted a genome-wide analysis of the genes that are regulated by RARs in mouse embryonic fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We found that in the absence of RA, RARs control the expression of several gene transcripts associated with cell adhesion. Consequently the knockout MEFs are unable to adhere and to spread on substrates and they display a disrupted network of actin filaments, compared with the WT cells. In contrast, in the presence of the ligand, RARs control the expression of other genes involved in signaling and in RA metabolism. Taking advantage of rescue cell lines expressing the RARα or RARγ subtypes (either wild-type or mutated at the N-terminal phosphorylation sites) in the null background, we found that the expression of RA-target genes can be controlled either by a specific single RAR or by a combination of RAR isotypes, depending on the gene. We also selected genes that require the phosphorylation of the receptors for their regulation by RA. Our results increase the repertoire of genes that are regulated by RARs and highlight the complexity and diversity of the transcriptional programs regulated by RARs, depending on the gene.

  16. Mass Varying Neutrinos in Supernovae

    CERN Document Server

    Rossi-Torres, F; de Holanda, P C; Peres, O L G

    2010-01-01

    We study limits for the mass varying neutrino model, using constrains from supernova neutrinos placed by the r-process condition, $Y_e<0.5$. Also, we use this model in a supernova environment to study the regions of survival probability in the oscillation space parameter ($\\tan^2\\theta$ and $\\Delta m^2_0$), considering the channel $\

  17. Esmaklassiline Karlovy Vary / Jaanus Noormets

    Index Scriptorium Estoniae

    Noormets, Jaanus

    2007-01-01

    Ilmar Raagi mängufilm "Klass" võitis 42. Karlovy Vary rahvusvahelise filmifestivalil kaks auhinda - ametliku kõrvalvõistlusprogrammi "East of the West" eripreemia "Special mention" ja Euroopa väärtfilmikinode keti Europa Cinemas preemia. Ka Asko Kase lühifilmi "Zen läbi prügi linastumisest ning teistest auhinnasaajatest ning osalejatest

  18. Optimistlik Karlovy Vary / Jaan Ruus

    Index Scriptorium Estoniae

    Ruus, Jaan, 1938-2017

    2007-01-01

    42. Karlovy Vary rahvusvahelise filmifestivali auhinnatud filmidest (žürii esimees Peter Bart). Kristallgloobuse sai Islandi-Saksamaa "Katseklaasilinn" (režii Baltasar Kormakur), parimaks režissööriks tunnistati norralane Bard Breien ("Negatiivse mõtlemise kunst"). Austraallase Michael James Rowlandi "Hea õnne teekond" sai žürii eripreemia

  19. Eestlased Karlovy Varys / J. R.

    Index Scriptorium Estoniae

    J. R.

    2007-01-01

    Ilmar Raagi mängufilm "Klass" osaleb 42. Karlovy Vary rahvusvahelise filmifestivali võistlusprogrammis "East of the West" ja Asko Kase lühimängufilm "Zen läbi prügi" on valitud festivali kõrvalprogrammi "Forum of Independents"

  20. Esmaklassiline Karlovy Vary / Jaanus Noormets

    Index Scriptorium Estoniae

    Noormets, Jaanus

    2007-01-01

    Ilmar Raagi mängufilm "Klass" võitis 42. Karlovy Vary rahvusvahelise filmifestivalil kaks auhinda - ametliku kõrvalvõistlusprogrammi "East of the West" eripreemia "Special mention" ja Euroopa väärtfilmikinode keti Europa Cinemas preemia. Ka Asko Kase lühifilmi "Zen läbi prügi linastumisest ning teistest auhinnasaajatest ning osalejatest

  1. Delay-independent stabilization for teleoperation with time varying delay

    OpenAIRE

    Fujita, Hiroyuki; Namerikawa, Toru

    2009-01-01

    This paper deals with the stability for nonlinear teleoperation with time varying communication delays. The proposed method is passivity-based controllers with time varying gains which depend on the rate of change of time varying delay. In our proposed method, stability condition is independent of the magnitude of the communication delay and the damping of the system. The delay-independent stability is shown via Lyapunov stability methods. Several experimental results show the effectiveness o...

  2. The astonishing diversity of Ig classes and B cell repertoires in teleost fish

    Directory of Open Access Journals (Sweden)

    Simon eFillatreau

    2013-02-01

    Full Text Available With lympoid tissue anatomy different than mammals, and diverse adaptations to all aquatic environments, fish constitute a fascinating group of vertebrate to study the biology of B cell repertoires in a comparative perspective. Fish B lymphocytes express immunoglobulin (Ig on their surface and secrete antigen-specific antibodies in response to immune challenges. Three antibody classes have been identified in fish, namely IgM, IgD and IgT, while IgG, IgA and IgE are absent. IgM and IgD have been found in all fish species analyzed, and thus seem to be primordial antibody classes. IgM and IgD are normally co-expressed from the same mRNA through alternative splicing, as in mammals. Tetrameric IgM is the main antibody class found in serum. Some species of fish also have IgT, which seems to exist only in fish and is specialized in mucosal immunity. IgM/IgD and IgT are expressed by two different sub-populations of B cells. The tools available to investigate B cell responses at the cellular level in fish are limited, but the progress of fish genomics has started to unravel a rich diversity of IgH and IgL locus organization, which might be related to the succcession of genome remodellings that occured during fish evolution. Moreover, the development of deep sequencing techniques has allowed the investigation of the global features of the expressed fish B cell repertoires in zebrafish and rainbow trout, in steady state or after infection. This review provides a description of the organization of fish Ig loci, with a particular emphasis on their heterogeneity between species, and presents recent data on the structure of the expressed Ig repertoire in healthy and infected fish.

  3. TRAV and TRBV repertoire, clonality and the proliferative history of umbilical cord blood T-cells.

    Science.gov (United States)

    Li, Yangqiu; Chen, Shaohua; Yang, Lijian; Yin, Qingsong; Geng, Suxia; Wu, Xiuli; Schmidt, Christian A; Przybylski, Grzegorz K

    2007-11-01

    Umbilical cord blood (CB) has been used successfully as a source of hematopoietic stem cells for transplantation. But the distribution and clonality of T-cell receptor alpha variable region (TRAV) and T-cell receptor beta variable region (TRBV) subfamily T-cells, the naïve T-cells level and the diversity of thymic recent output function in CB has not been yet clearly defined. In order to characterize the repertoire of CB T-cells, the CDR3 of 29 TRAV and 24 TRBV subfamily genes were analyzed in T-cells from 12 cord blood samples, using RT-PCR and genescan technique. To determine the proliferative history of CB T-cells, quantitative analysis of deltaRec-psiJalpha signal joint T-cell receptor excision circles (sjTRECs) was performed in mononuclear cells, CD3+, CD4+ and CD8+ T-cells from 20 CB samples by real-time PCR. In addition the analysis of 23 TRBV-TRBD1 sjTRECs in 10 cases of CB CD4+ T-cells and CB CD8+ T-cells was performed by semi-nested PCR. We found a marked restriction of TRBV expression pattern in CBMCs compared to peripheral blood mononuclear cells (PBMC), which expressed all 24 TRBV genes. All PCR products of TRAV and TRBV subfamilies from CB, except for 3 cases, displayed polyclonal rearrangement pattern. The deltaRec-psiJalpha sjTRECs counts were significantly higher in CB, than in PB samples. Also the number of detectable TRBV sjTRECs was higher in CB than in peripheral blood. In conclusion, our results indicate polyclonal but restricted repertoire and a very short proliferative history of CB T-cells. The incomplete repertoire and naivety of CB T-cells might be the reason that CB hematopoietic stem cells transplant recipients are less likely to develop graft vs host disease.

  4. The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases.

    Science.gov (United States)

    Chardès, Thierry; Chapal, Nicolas; Bresson, Damien; Bès, Cédric; Giudicelli, Véronique; Lefranc, Marie-Paule; Péraldi-Roux, Sylvie

    2002-06-01

    Human anti-thyroid peroxidase (TPO) autoantibodies (aAb) are generated during autoimmune thyroid diseases (AITD). Within recent years, increasing knowledge of the TPO-specific aAb repertoire, gained mainly by the use of combinatorial library methodology, has led to the cloning and sequencing of around 180 human anti-TPO aAb. Analysis of the immunoglobulin (Ig) variable (V) genes encoding the TPO aAb in the ImMunoGeneTics database (IMGT) (http://imgt.cines.fr) reveals major features of the TPO-directed aAb repertoire during AITD. Heavy chain VH domains of TPO-specific aAb from Graves' disease patients preferentially use D proximal IGHV1 genes, whereas those from Hashimoto's thyroiditis are characterized more frequently by IGHV3 genes, mainly located in the middle of the IGH locus. A large proportion of the anti-TPO heavy chain VH domains is obtained following a VDJ recombination process that uses inverted D genes. J distal IGKV1 and IGLV1 genes are predominantly used in TPO aAb. In contrast to the numerous somatic hypermutations in the TPO-specific heavy chains, there is only limited amino acid replacement in most of the TPO-specific light chains, particularly in those encoded by J proximal IGLV or IGKV genes, suggesting that a defect in receptor editing can occur during aAb generation in AITD. Among the predominant IGHV1 or IGKV1 TPO aAb, conserved somatic mutations are the hallmark of the TPO aAb repertoire. The aim of this review is to provide new insights into aAb generation against TPO, a major autoantigen involved in AITD.

  5. Comparative Analysis of Immune Repertoires between Bactrian Camel's Conventional and Heavy-Chain Antibodies

    Science.gov (United States)

    Yang, Kai; Zhang, Wei; Zhang, Changjiang; Fu, Longfei; Ren, Zhe; Wang, Changxi; Wu, Jinghua; Lu, Ruxue; Ye, Yanrui; He, Mengying; Nie, Chao; Yang, Naibo; Wang, Jian; Yang, Huanming; Liu, Xiao

    2016-01-01

    Compared to classical antibodies, camel heavy chain antibodies (HCAbs) are smaller in size due to lack of the light chain and the first constant domain of the heavy chain (CH1 region). The variable regions of HCAbs (VHHs) are more soluble and stable than that of conventional antibodies (VHs). Even with such simple structure, they are still functional in antigen binding. Although HCAbs have been extensively investigated over the past two decades, most efforts have been based upon low throughput sequence analysis, and there are only limited reports trying to analyze and describe the complete immune repertoire (IR) of camel HCAbs. Here we leveraged the high-throughput data generated by Next Generation Sequencing (NGS) of the variable domains of the antibody heavy chains from three Bactrian camels to conduct in-depth comparative analyses of the immunoglobulin repertoire. These include analyses of the complementary determining region 3 (CDR3) length and distribution, mutation rate, antibody characteristic amino acids, the distribution of the cysteine (Cys) codons, and the non-classical VHHs. We found that there is higher diversity in the CDR2 than in the other sub-regions, and there is a higher mutation rate in the VHHs than in the VHs (P VH and VHH clones, we also observed other substitutions at the positions NO.40/54/57/96/101 that could lead to additional structural alterations. We also found that VH-derived VHH clones, referred to as non-classical VHH clones in this study, accounted for about 8% of all clones. Further, only 5%-10% clones had the Trp > Arg AA substitution at the first position of framework 4 for all types of clones. We present, for the first time, a relatively complete picture of the Bactrian camel antibody immune repertoire, including conventional antibody (Ab) and HCAbs, using PCR and in silico analysis based on high-throughput NGS data. PMID:27588755

  6. Genomic variation in the vomeronasal receptor gene repertoires of inbred mice

    Directory of Open Access Journals (Sweden)

    Wynn Elizabeth H

    2012-08-01

    Full Text Available Abstract Background Vomeronasal receptors (VRs, expressed in sensory neurons of the vomeronasal organ, are thought to bind pheromones and mediate innate behaviours. The mouse reference genome has over 360 functional VRs arranged in highly homologous clusters, but the vast majority are of unknown function. Differences in these receptors within and between closely related species of mice are likely to underpin a range of behavioural responses. To investigate these differences, we interrogated the VR gene repertoire from 17 inbred strains of mice using massively parallel sequencing. Results Approximately half of the 6222 VR genes that we investigated could be successfully resolved, and those that were unambiguously mapped resulted in an extremely accurate dataset. Collectively VRs have over twice the coding sequence variation of the genome average; but we identify striking non-random distribution of these variants within and between genes, clusters, clades and functional classes of VRs. We show that functional VR gene repertoires differ considerably between different Mus subspecies and species, suggesting these receptors may play a role in mediating behavioural adaptations. Finally, we provide evidence that widely-used, highly inbred laboratory-derived strains have a greatly reduced, but not entirely redundant capacity for differential pheromone-mediated behaviours. Conclusions Together our results suggest that the unusually variable VR repertoires of mice have a significant role in encoding differences in olfactory-mediated responses and behaviours. Our dataset has expanded over nine fold the known number of mouse VR alleles, and will enable mechanistic analyses into the genetics of innate behavioural differences in mice.

  7. Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

    Directory of Open Access Journals (Sweden)

    Mathieu Angin

    Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

  8. 免疫组库的临床应用%Immune repertoire in clinic application

    Institute of Scientific and Technical Information of China (English)

    付钰; 杨国胜; 吴松

    2014-01-01

    Immune repertoire refers to the summation of the polymorphism of all functional diversity of B cells or T cells in the circulatory system of an individual at any given time.Through 5'RACE or multiplex PCR technology,immune repertoire sequencing technology can capture the complementary determining region that has the highest polymorphism in immunoglobulin heavy chain (IGH) or the beta region of T cell receptor,and then high-depth sequencing is conducted.Polymorphism of B cells or T cells is the highlight of today's study.Immune repertoire sequencing can be applied to the development of vaccines and medicines,the discovery of biomarkers,the detection of minimal residual disease (MRD),the research of autoimmune diseases,and monitoring transplantation.%免疫组库是指在任何指定时间内,某个个体的循环系统中所有功能多样性B细胞或者T细胞的多态性总和.免疫组库测序技术就是通过5' RACE或者多重PCR技术将免疫球蛋白重链(IGH)或者T细胞受体beta区多态性最高的互补决定区(CDR3)捕获下来,然后进行高深度测序,研究B细胞或者T细胞的多态性,是当今一大研究亮点.免疫组库测序可以应用于医药和疫苗的研发、生物标志物的发现、微小残留病(MRD)检测、自身免疫性疾病的研究以及移植后监测等领域,因而具有重大意义.

  9. An Expressive Bodily Movement Repertoire for Marimba Performance, Revealed through Observers' Laban Effort-Shape Analyses, and Allied Musical Features: Two Case Studies.

    Science.gov (United States)

    Broughton, Mary C; Davidson, Jane W

    2016-01-01

    Musicians' expressive bodily movements can influence observers' perception of performance. Furthermore, individual differences in observers' music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies-one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers' perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players' bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the types and locations of actions

  10. An expressive bodily movement repertoire for marimba performance, revealed through observers’ Laban effort-shape analyses, and allied musical features: two case studies

    Directory of Open Access Journals (Sweden)

    Mary C Broughton

    2016-08-01

    Full Text Available Musicians’ expressive bodily movements can influence observers’ perception of performance. Furthermore, individual differences in observers’ music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies – one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers’ perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players’ bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the

  11. An Expressive Bodily Movement Repertoire for Marimba Performance, Revealed through Observers' Laban Effort-Shape Analyses, and Allied Musical Features: Two Case Studies

    Science.gov (United States)

    Broughton, Mary C.; Davidson, Jane W.

    2016-01-01

    Musicians' expressive bodily movements can influence observers' perception of performance. Furthermore, individual differences in observers' music and motor expertise can shape how they perceive and respond to music performance. However, few studies have investigated the bodily movements that different observers of music performance perceive as expressive, in order to understand how they might relate to the music being produced, and the particular instrument type. In this paper, we focus on marimba performance through two case studies—one solo and one collaborative context. This study aims to investigate the existence of a core repertoire of marimba performance expressive bodily movements, identify key music-related features associated with the core repertoire, and explore how observers' perception of expressive bodily movements might vary according to individual differences in their music and motor expertise. Of the six professional musicians who observed and analyzed the marimba performances, three were percussionists and experienced marimba players. Following training, observers implemented the Laban effort-shape movement analysis system to analyze marimba players' bodily movements that they perceived as expressive in audio-visual recordings of performance. Observations that were agreed by all participants as being the same type of action at the same location in the performance recording were examined in each case study, then across the two studies. A small repertoire of bodily movements emerged that the observers perceived as being expressive. Movements were primarily allied to elements of the music structure, technique, and expressive interpretation, however, these elements appeared to be interactive. A type of body sway movement and more localized sound generating actions were perceived as expressive. These movements co-occurred and also appeared separately. Individual participant data revealed slightly more variety in the types and locations of actions

  12. Contrasted Evolution of the Vomeronasal Receptor Repertoires in Mammals and Squamate Reptiles

    OpenAIRE

    Brykczynska, Urszula; Tzika, Athanasia C; Rodriguez, Ivan; Michel C Milinkovitch

    2013-01-01

    The vomeronasal organ (VNO) is an olfactory structure that detects pheromones and environmental cues. It consists of sensory neurons that express evolutionary unrelated groups of transmembrane chemoreceptors. The predominant V1R and V2R receptor repertoires are believed to detect airborne and water-soluble molecules, respectively. It has been suggested that the shift in habitat of early tetrapods from water to land is reflected by an increase in the ratio of V1R/V2R genes. Snakes, which have ...

  13. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

    DEFF Research Database (Denmark)

    Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo

    2016-01-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high...... of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models....

  14. Behavioural repertoire of working donkeys and consistency of behaviour over time, as a preliminary step towards identifying pain-related behaviours.

    Directory of Open Access Journals (Sweden)

    Fran H Regan

    Full Text Available The donkey has a reputation for stoicism and its behavioural repertoire in clinical contexts is under-reported. Lack of understanding of the norms of donkey behaviour and how it may vary over time can compromise use of behavioural measures as indicators of pain or emotional state. The objective of this study was to find out whether the behaviour of working donkeys was influenced by gender, the time of day or differed between days with a view to assessing how robust these measures are for inclusion in a working donkey ethogram.Frequency and consistency of postural and event behaviours were measured in 21 adult working donkeys (12 females; 9 males. Instantaneous (scan and focal sampling were used to measure maintenance, lying, ingestive and investigative behaviours at hourly intervals for ten sessions on each of two consecutive days. High head carriage and biting were seen more frequently in male donkeys than females (P<0.001. Level head carriage, licking/chewing and head-shaking were observed more frequently in female donkeys (P<0.001. Tail position, ear orientation, foot stamping, rolling/lying and head-shaking behaviours were affected by time of day (P<0.001. However, only two variations in ear orientation were found to be significantly different over the two days of observations (P<0.001. Tail swishing, head shaking, foot stamping, and ears held sideways and downwards were significantly correlated (P<0.001 and are assumed to be behaviours to discourage flies.All donkeys expressed an extensive behavioural repertoire, although some differences in behaviour were evident between genders. While most behaviours were consistent over time, some behaviours were influenced by time of day. Few behaviours differed between the two test days. The findings can be used to inform the development of a robust, evidence-based ethogram for working donkeys.

  15. Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire.

    Science.gov (United States)

    Briney, Bryan S; Willis, Jordan R; Hicar, Mark D; Thomas, James W; Crowe, James E

    2012-09-01

    Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5') position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus.

  16. New varying speed of light theories

    CERN Document Server

    Magueijo, J

    2003-01-01

    We review recent work on the possibility of a varying speed of light (VSL). We start by discussing the physical meaning of a varying $c$, dispelling the myth that the constancy of $c$ is a matter of logical consistency. We then summarize the main VSL mechanisms proposed so far: hard breaking of Lorentz invariance; bimetric theories (where the speeds of gravity and light are not the same); locally Lorentz invariant VSL theories; theories exhibiting a color dependent speed of light; varying $c$ induced by extra dimensions (e.g. in the brane-world scenario); and field theories where VSL results from vacuum polarization or CPT violation. We show how VSL scenarios may solve the cosmological problems usually tackled by inflation, and also how they may produce a scale-invariant spectrum of Gaussian fluctuations, capable of explaining the WMAP data. We then review the connection between VSL and theories of quantum gravity, showing how ``doubly special'' relativity has emerged as a VSL effective model of quantum space...

  17. Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy.

    Science.gov (United States)

    Zandian, Arash; Forsström, Björn; Häggmark-Månberg, Anna; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter; Ayoglu, Burcu

    2017-02-09

    The underlying molecular mechanisms of autoimmune diseases are poorly understood. To unravel the autoimmune processes across diseases, comprehensive and unbiased analyses of proteins targets recognized by the adaptive immune system are needed. Here we present an approach starting from high-density peptide arrays to characterize autoantibody repertoires and to identify new autoantigens. A set of ten plasma and serum samples from subjects with multiple sclerosis, narcolepsy, and without any disease diagnosis were profiled on a peptide array representing the whole proteome, hosting 2.2 million 12-mer peptides with a six amino acid lateral shift. On the basis of the IgG reactivities found on these whole-proteome peptide microarrays, a set of 23 samples was then studied on a targeted array with 174 000 12-mer peptides of single amino acid lateral shift. Finally, verification of IgG reactivities was conducted with a larger sample set (n = 448) using the bead-based peptide microarrays. The presented workflow employed three different peptide microarray formats to discover and resolve the epitopes of human autoantibodies and revealed two potentially new autoantigens: MAP3K7 in multiple sclerosis and NRXN1 in narcolepsy. The presented strategy provides insights into antibody repertoire reactivity at a peptide level and may accelerate the discovery and validation of autoantigens in human diseases.

  18. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Science.gov (United States)

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function. PMID:28246613

  19. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function

    Directory of Open Access Journals (Sweden)

    Silvana Balzar

    2017-01-01

    Full Text Available Idiopathic chronic inflammatory conditions (ICIC such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system’s thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system’s compartmentalization in the pathogenesis of ICIC. The CDR concept’s relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

  20. Birds Generally Carry a Small Repertoire of Bitter Taste Receptor Genes.

    Science.gov (United States)

    Wang, Kai; Zhao, Huabin

    2015-09-04

    As they belong to the most species-rich class of tetrapod vertebrates, birds have long been believed to possess an inferior taste system. However, the bitter taste is fundamental in birds to recognize dietary toxins (which are typically bitter) in potential food sources. To characterize the evolution of avian bitter taste receptor genes (Tas2rs) and to test whether dietary toxins have shaped the repertoire size of avian Tas2rs, we examined 48 genomes representing all but 3 avian orders. The total number of Tas2r genes was found to range from 1 in the domestic pigeon to 12 in the bar-tailed trogon, with an average of 4, which suggested that a much smaller Tas2r gene repertoire exists in birds than in other vertebrates. Furthermore, we uncovered a positive correlation between the number of putatively functional Tas2rs and the abundance of potential toxins in avian diets. Because plant products contain more toxins than animal tissues and insects release poisonous defensive secretions, we hypothesized that herbivorous and insectivorous birds may demand more functional Tas2rs than carnivorous birds feeding on noninsect animals. Our analyses appear to support this hypothesis and highlight the critical role of taste perception in birds.

  1. The MicroRNA Repertoire of Symbiodinium, the Dinoflagellate Symbiont of Reef-Building Corals

    KAUST Repository

    Baumgarten, Sebastian

    2013-07-01

    Animal and plant genomes produce numerous small RNAs (smRNAs) that regulate gene expression post-transcriptionally affecting metabolism, development, and epigenetic inheritance. In order to characterize the repertoire of endogenous microRNAs and potential gene targets, we conducted smRNA and mRNA expression profiling over nine experimental treatments of cultures from the dinoflagellate Symbiodinium sp. A1, a photosynthetic symbiont of scleractinian corals. We identified a total of 75 novel smRNAs in Symbiodinum sp. A1 that share stringent key features with functional microRNAs from other model organisms. A subset of 38 smRNAs was predicted independently over all nine treatments and their putative gene targets were identified. We found 3,187 animal-like target sites in the 3’UTRs of 12,858 mRNAs and 53 plantlike target sites in 51,917 genes. Furthermore, we identified the core RNAi protein machinery in Symbiodinium. Integration of smRNA and mRNA expression profiling identified a variety of processes that could be under microRNA control, e.g. regulation of translation, DNA modification, and chromatin silencing. Given that Symbiodinium seems to have a paucity of transcription factors and differentially expressed genes, identification and characterization of its smRNA repertoire establishes the possibility of a range of gene regulatory mechanisms in dinoflagellates acting post-transcriptionally.

  2. The acoustic repertoire of bottlenose dolphins (Tursiops truncatus) from the southern Gulf of Mexico

    Science.gov (United States)

    Bazua-Duran, Carmen

    2005-04-01

    Bottlenose dolphins live in a variety of habitats of the world's oceans using their acoustic repertoire to communicate and inspect their environment. This work investigates the acoustic repertoire of bottlenose dolphins that inhabit a coastal lagoon of the southern Gulf of Mexico, the Laguna de Terminos and how it may relate to the dolphins' general behavioral state and herd size, and to the general characteristics of the habitat, such as visibility, depth, and sea state. Preliminary results show that bottlenose dolphins produce by far more clicks than whistles in all behavioral states (feeding, resting, social, and travel) and herd sizes, which may correlate with the decreased visibility and shallow depth of the Laguna de Terminos. Additionally, silence was found during all behavioral states, but very seldom in herds of large size. These preliminary results suggest that bottlenose dolphins are choosing when and where to produce their phonations. Therefore, more detailed studies are needed to understand how these animals are using their acoustic sense to communicate and inspect their environment. [Work supported by CONACyT-Gobierno Edo. de Campeche and PAPIIT, UNAM.

  3. The repertoire of G-protein-coupled receptors in Xenopus tropicalis

    Directory of Open Access Journals (Sweden)

    Hu Yinghe

    2009-06-01

    Full Text Available Abstract Background The G-protein-coupled receptor (GPCR superfamily represents the largest protein family in the human genome. These proteins have a variety of physiological functions that give them well recognized roles in clinical medicine. In Xenopus tropicalis, a widely used animal model for physiology research, the repertoire of GPCRs may help link the GPCR evolutionary history in vertebrates from teleost fish to mammals. Results We have identified 1452 GPCRs in the X. tropicalis genome. Phylogenetic analyses classified these receptors into the following seven families: Glutamate, Rhodopsin, Adhesion, Frizzled, Secretin, Taste 2 and Vomeronasal 1. Nearly 70% of X. tropicalis GPCRs are represented by the following three types of receptors thought to receive chemosensory information from the outside world: olfactory, vomeronasal 1 and vomeronasal 2 receptors. Conclusion X. tropicalis shares a more similar repertoire of GPCRs with mammals than it does with fish. An examination of the three major groups of receptors related to olfactory/pheromone detection shows that in X. tropicalis, these groups have undergone lineage specific expansion. A comparison of GPCRs in X. tropicalis, teleost fish and mammals reveals the GPCR evolutionary history in vertebrates.

  4. Unique Features of Fish Immune Repertoires: Particularities of Adaptive Immunity Within the Largest Group of Vertebrates.

    Science.gov (United States)

    Magadan, Susana; Sunyer, Oriol J; Boudinot, Pierre

    2015-01-01

    Fishes (i.e., teleost fishes) are the largest group of vertebrates. Although their immune system is based on the fundamental receptors, pathways, and cell types found in all groups of vertebrates, fishes show a diversity of particular features that challenge some classical concepts of immunology. In this chapter, we discuss the particularities of fish immune repertoires from a comparative perspective. We examine how allelic exclusion can be achieved when multiple Ig loci are present, how isotypic diversity and functional specificity impact clonal complexity, how loss of the MHC class II molecules affects the cooperation between T and B cells, and how deep sequencing technologies bring new insights about somatic hypermutation in the absence of germinal centers. The unique coexistence of two distinct B-cell lineages respectively specialized in systemic and mucosal responses is also discussed. Finally, we try to show that the diverse adaptations of immune repertoires in teleosts can help in understanding how somatic adaptive mechanisms of immunity evolved in parallel in different lineages across vertebrates.

  5. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

    Directory of Open Access Journals (Sweden)

    Fan Gao

    Full Text Available In human immune system, V(DJ recombination produces an enormously large repertoire of immunoglobulins (Ig so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(DJ recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(DJ recombination within a day by personal genome sequencers.

  6. High Throughput Sequencing of T Cell Antigen Receptors Reveals a Conserved TCR Repertoire

    Science.gov (United States)

    Hou, Xianliang; Lu, Chong; Chen, Sisi; Xie, Qian; Cui, Guangying; Chen, Jianing; Chen, Zhi; Wu, Zhongwen; Ding, Yulong; Ye, Ping; Dai, Yong; Diao, Hongyan

    2016-01-01

    Abstract The T-cell receptor (TCR) repertoire is a mirror of the human immune system that reflects processes caused by infections, cancer, autoimmunity, and aging. Next-generation sequencing has become a powerful tool for deep TCR profiling. Herein, we used this technology to study the repertoire features of TCR beta chain in the blood of healthy individuals. Peripheral blood samples were collected from 10 healthy donors. T cells were isolated with anti-human CD3 magnetic beads according to the manufacturer's protocol. We then combined multiplex-PCR, Illumina sequencing, and IMGT/High V-QUEST to analyze the characteristics and polymorphisms of the TCR. Most of the individual T cell clones were present at very low frequencies, suggesting that they had not undergone clonal expansion. The usage frequencies of the TCR beta variable, beta joining, and beta diversity gene segments were similar among T cells from different individuals. Notably, the usage frequency of individual nucleotides and amino acids within complementarity-determining region (CDR3) intervals was remarkably consistent between individuals. Moreover, our data show that terminal deoxynucleotidyl transferase activity was biased toward the insertion of G (31.92%) and C (27.14%) over A (21.82%) and T (19.12%) nucleotides. Some conserved features could be observed in the composition of CDR3, which may inform future studies of human TCR gene recombination. PMID:26962778

  7. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.

    Science.gov (United States)

    Cicin-Sain, Luka; Smyk-Pearson, Susan; Smyk-Paerson, Sue; Currier, Noreen; Byrd, Laura; Koudelka, Caroline; Robinson, Tammie; Swarbrick, Gwendolyn; Tackitt, Shane; Legasse, Alfred; Fischer, Miranda; Nikolich-Zugich, Dragana; Park, Byung; Hobbs, Theodore; Doane, Cynthia J; Mori, Motomi; Axthelm, Michael K; Axthelm, Michael T; Lewinsohn, Deborah A; Nikolich-Zugich, Janko

    2010-06-15

    Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.

  8. Colour-Blind: Discursive Repertoires Teachers Used to Story Racism and Aboriginality in Urban Prairie Schools

    Directory of Open Access Journals (Sweden)

    Tyler McCreary

    2011-12-01

    Full Text Available This qualitative study explores how teachers' constructions of racism consistently minimized its pervasiveness in the school. Teachers constructed racism as individual not systemic, construed it as a phenomenon of places outside the school, and attributed responsibility for addressing racism to other people, particularly Aboriginal populations. Based on written responses from 95 Canadian Prairie teachers from two schools, this research examines the discourses teachers employed to narrate racism, particularly with relation to Aboriginal students. While there were some differences between inner city and suburban teachers, teachers from both environments followed discursive repertoires that absolved themselves of responsibility for addressing racism and maintained the colour-blind image of education. Interrogating these discursive repertoires exposes the systems of denial that block meaningful action upon racialized inequalities and prevent the development of a truly inclusive educational environment. This underlines the need for expanded anti-racist professional development to support critical racial reflexivity among in-service teachers.Keywords: racism in education; critical whiteness studies; in-service teachers; Aboriginal education

  9. The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

    Science.gov (United States)

    Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

    2004-02-01

    In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

  10. Harmonic functions with varying coefficients

    Directory of Open Access Journals (Sweden)

    Jacek Dziok

    2016-05-01

    Full Text Available Abstract Complex-valued harmonic functions that are univalent and sense preserving in the open unit disk can be written in the form f = h + g ‾ $f=h+\\overline{g}$ , where h and g are analytic. In this paper we investigate some classes of univalent harmonic functions with varying coefficients related to Janowski functions. By using the extreme points theory we obtain necessary and sufficient convolution conditions, coefficients estimates, distortion theorems, and integral mean inequalities for these classes of functions. The radii of starlikeness and convexity for these classes are also determined.

  11. Linearized Bekenstein Varying Alpha Models

    CERN Document Server

    Pina-Avelino, P; Oliveira, J C

    2004-01-01

    We study the simplest class of Bekenstein-type, varying $\\alpha$ models, in which the two available free functions (potential and gauge kinetic function) are Taylor-expanded up to linear order. Any realistic model of this type reduces to a model in this class for a certain time interval around the present day. Nevertheless, we show that no such model is consistent with all existing observational results. We discuss possible implications of these findings, and in particular clarify the ambiguous statement (often found in the literature) that ``the Webb results are inconsistent with Oklo''.

  12. Linearized Bekenstein varying α models

    Science.gov (United States)

    Avelino, P. P.; Martins, C. J.; Oliveira, J. C.

    2004-10-01

    We study the simplest class of Bekenstein-type, varying α models, in which the two available free functions (potential and gauge kinetic function) are Taylor-expanded up to linear order. Any realistic model of this type reduces to a model in this class for a certain time interval around the present day. Nevertheless, we show that no such model is consistent with all existing observational results. We discuss possible implications of these findings, and, in particular, clarify the ambiguous statement (often found in the literature) that “the Webb results are inconsistent with Oklo.”

  13. Time-varying cosmological term

    Science.gov (United States)

    Socorro, J.; D'oleire, M.; Pimentel, Luis O.

    2015-11-01

    We present the case of time-varying cosmological term using the Lagrangian formalism characterized by a scalar field ϕ with standard kinetic energy and arbitrary potential V(ϕ). This model is applied to Friedmann-Robertson-Walker (FRW)cosmology. Exact solutions of the field equations are obtained by a special ansats to solve the Einstein-Klein-Gordon equation and a particular potential for the scalar field and barotropic perfect fluid. We present the evolution on this cosmological term with different scenarios.

  14. New varying speed of light theories

    Energy Technology Data Exchange (ETDEWEB)

    Magueijo, Joao [Blackett Laboratory, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2BZ (United Kingdom)

    2003-11-01

    We review recent work on the possibility of a varying speed of light (VSL). We start by discussing the physical meaning of a varying-c, dispelling the myth that the constancy of c is a matter of logical consistency. We then summarize the main VSL mechanisms proposed so far: hard breaking of Lorentz invariance; bimetric theories (where the speeds of gravity and light are not the same); locally Lorentz invariant VSL theories; theories exhibiting a colour-dependent speed of light; varying-c induced by extra dimensions (e.g. in the brane-world scenario); and field theories where VSL results from vacuum polarization or CPT violation. We show how VSL scenarios may solve the cosmological problems usually tackled by inflation, and also how they may produce a scale-invariant spectrum of Gaussian fluctuations, capable of explaining the WMAP data. We then review the connection between VSL and theories of quantum gravity, showing how 'doubly special' relativity has emerged as a VSL effective model of quantum space-time, with observational implications for ultra-high energy cosmic rays (UHECRs) and gamma ray bursts. Some recent work on the physics of 'black' holes and other compact objects in VSL theories is also described, highlighting phenomena associated with spatial (as opposed to temporal) variations in c. Finally, we describe the observational status of the theory. The evidence is currently slim-redshift dependence in the atomic fine structure, anomalies with UHECRs, and (to a much lesser extent) the acceleration of the universe and the WMAP data. The constraints (e.g. those arising from nucleosynthesis or geological bounds) are tight but not insurmountable. We conclude with the observational predictions of the theory and the prospects for its refutation or vindication.

  15. New varying speed of light theories

    Science.gov (United States)

    Magueijo, João

    2003-11-01

    We review recent work on the possibility of a varying speed of light (VSL). We start by discussing the physical meaning of a varying-c, dispelling the myth that the constancy of c is a matter of logical consistency. We then summarize the main VSL mechanisms proposed so far: hard breaking of Lorentz invariance; bimetric theories (where the speeds of gravity and light are not the same); locally Lorentz invariant VSL theories; theories exhibiting a colour-dependent speed of light; varying-c induced by extra dimensions (e.g. in the brane-world scenario); and field theories where VSL results from vacuum polarization or CPT violation. We show how VSL scenarios may solve the cosmological problems usually tackled by inflation, and also how they may produce a scale-invariant spectrum of Gaussian fluctuations, capable of explaining the WMAP data. We then review the connection between VSL and theories of quantum gravity, showing how 'doubly special' relativity has emerged as a VSL effective model of quantum space-time, with observational implications for ultra-high energy cosmic rays (UHECRs) and gamma ray bursts. Some recent work on the physics of 'black' holes and other compact objects in VSL theories is also described, highlighting phenomena associated with spatial (as opposed to temporal) variations in c. Finally, we describe the observational status of the theory. The evidence is currently slim—redshift dependence in the atomic fine structure, anomalies with UHECRs, and (to a much lesser extent) the acceleration of the universe and the WMAP data. The constraints (e.g. those arising from nucleosynthesis or geological bounds) are tight but not insurmountable. We conclude with the observational predictions of the theory and the prospects for its refutation or vindication.

  16. Time Varying Market Integration and Expected Rteurns in Emerging Markets

    NARCIS (Netherlands)

    de Jong, F.C.J.M.; de Roon, F.A.

    2001-01-01

    We use a simple model in which the expected returns in emerging markets depend on their systematic risk as measured by their beta relative to the world portfolio as well as on the level of integration in that market.The level of integration is a time-varying variable that depends on the market value

  17. Local Varying-Alpha Theories

    CERN Document Server

    Barrow, John D

    2014-01-01

    In a recent paper we demonstrated how the simplest model for varying alpha may be interpreted as the effect of a dielectric material, generalized to be consistent with Lorentz invariance. Unlike normal dielectrics, such a medium cannot change the speed of light, and its dynamics obey a Klein-Gordon equation. This work immediately suggests an extension of the standard theory, even if we require compliance with Lorentz invariance. Instead of a wave equation, the dynamics may satisfy a local algebraic relation involving the permittivity and the properties of the electromagnetic field, in analogy with more conventional dielectric (but still preserving Lorentz invariance). We develop the formalism for such theories and investigate some phenomenological implications. The problem of the divergence of the classical self-energy can be solved, or at least softened, in this framework. Some interesting new cosmological solutions for the very early universe are found, including the possibility of a bounce, inflation and e...

  18. Exploration of Periodically Varying Graphs

    CERN Document Server

    Flocchini, Paola; Santoro, Nicola

    2009-01-01

    We study the computability and complexity of the exploration problem in a class of highly dynamic graphs: periodically varying (PV) graphs, where the edges exist only at some (unknown) times defined by the periodic movements of carriers. These graphs naturally model highly dynamic infrastructure-less networks such as public transports with fixed timetables, low earth orbiting (LEO) satellite systems, security guards' tours, etc. We establish necessary conditions for the problem to be solved. We also derive lower bounds on the amount of time required in general, as well as for the PV graphs defined by restricted classes of carriers movements: simple routes, and circular routes. We then prove that the limitations on computability and complexity we have established are indeed tight. In fact we prove that all necessary conditions are also sufficient and all lower bounds on costs are tight. We do so constructively presenting two worst case optimal solution algorithms, one for anonymous systems, and one for those w...

  19. Weighted approximation with varying weight

    CERN Document Server

    Totik, Vilmos

    1994-01-01

    A new construction is given for approximating a logarithmic potential by a discrete one. This yields a new approach to approximation with weighted polynomials of the form w"n"(" "= uppercase)P"n"(" "= uppercase). The new technique settles several open problems, and it leads to a simple proof for the strong asymptotics on some L p(uppercase) extremal problems on the real line with exponential weights, which, for the case p=2, are equivalent to power- type asymptotics for the leading coefficients of the corresponding orthogonal polynomials. The method is also modified toyield (in a sense) uniformly good approximation on the whole support. This allows one to deduce strong asymptotics in some L p(uppercase) extremal problems with varying weights. Applications are given, relating to fast decreasing polynomials, asymptotic behavior of orthogonal polynomials and multipoint Pade approximation. The approach is potential-theoretic, but the text is self-contained.

  20. Varying electric charge in multi-scale spacetimes

    CERN Document Server

    Calcagni, Gianluca; Fernández, David Rodríguez

    2014-01-01

    We derive the covariant equations of motion for Maxwell field theory and electrodynamics in multi-scale spacetimes with weighted Laplacian. An effective spacetime-dependent electric charge of geometric origin naturally emerges from the theory, thus giving rise to a varying fine-structure constant. The theory is compared with other varying-coupling models, such as those with a varying electric charge or varying speed of light. The theory is also confronted with cosmological observations, which can place constraints on the characteristic scales in the multi-fractional measure. We note that the model considered here is fundamentally different from those previously proposed in the literature, either of the varying-e or varying-c persuasion.

  1. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals.

    Science.gov (United States)

    Niimura, Yoshihito; Matsui, Atsushi; Touhara, Kazushige

    2014-09-01

    Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory. © 2014 Niimura et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Cultural repertoires and food-related household technology within colonia households under conditions of material hardship

    Directory of Open Access Journals (Sweden)

    Dean Wesley R

    2012-05-01

    Full Text Available Abstract Introduction Mexican-origin women in the U.S. living in colonias (new-destination Mexican-immigrant communities along the Texas-Mexico border suffer from a high incidence of food insecurity and diet-related chronic disease. Understanding environmental factors that influence food-related behaviors among this population will be important to improving the well-being of colonia households. This article focuses on cultural repertoires that enable food choice and the everyday uses of technology in food-related practice by Mexican-immigrant women in colonia households under conditions of material hardship. Findings are presented within a conceptual framework informed by concepts drawn from sociological accounts of technology, food choice, culture, and material hardship. Methods Field notes were provided by teams of promotora-researchers (indigenous community health workers and public-health professionals trained as participant observers. They conducted observations on three separate occasions (two half-days during the week and one weekend day within eight family residences located in colonias near the towns of Alton and San Carlos, Texas. English observations were coded inductively and early observations stressed the importance of technology and material hardship in food-related behavior. These observations were further explored and coded using the qualitative data package Atlas.ti. Results Technology included kitchen implements used in standard and adapted configurations and household infrastructure. Residents employed tools across a range of food-related activities identified as forms of food acquisition, storage, preparation, serving, feeding and eating, cleaning, and waste processing. Material hardships included the quality, quantity, acceptability, and uncertainty dimensions of food insecurity, and insufficient consumption of housing, clothing and medical care. Cultural repertoires for coping with material hardship included reliance on

  3. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

    DEFF Research Database (Denmark)

    Ostrov, David A; Grant, Barry J; Pompeu, Yuri A;

    2012-01-01

    studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA...... molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8(+) T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains...... unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T...

  4. Behavioral repertoire of the giant freshwater prawn Macrobrachium rosenbergii (De Man, 1879 in laboratory

    Directory of Open Access Journals (Sweden)

    Daniele Bezerra dos Santos

    2016-09-01

    Full Text Available An ethogram was prepared to characterize and describe the behavior of the prawn Macrobrachium rosenbergii in the laboratory so that its behavior would foreground in-depth analysis of the species´s culture. Sixty prawns were observed during 30 days through the ad libitum method, featuring one-hour continuous reports, at 07:00-08:00; 08:30-09:30; 10:00-11:00; 11:30-12:30; 13:00-14:00; 14:30-15:30; 16:00-17:00; 17:30-18:30. M. rosenbergii developed several behavioral activities with 28 categories and grouped in activity classes, such as, maintenance, locomotion, feeding and agonism. Characterization, description and understanding of the behavioral repertoire of M. rosenbergii through methodologies and observation tools typical of behavioral studies are an important step towards the improvement of technical management and welfare of the animal in captivity.

  5. Generation and isolation of target-specific single-domain antibodies from shark immune repertoires.

    Science.gov (United States)

    Müller, Mischa Roland; O'Dwyer, Ronan; Kovaleva, Marina; Rudkin, Fiona; Dooley, Helen; Barelle, Caroline Jane

    2012-01-01

    The drive to exploit novel targets and biological pathways has lead to the expansion of classical antibody research into innovative fragment adaptations and novel scaffolds. The hope being that alternative or cryptic epitopes may be targeted, tissue inaccessibility may be overcome, and easier engineering options will facilitate multivalent, multi-targeting approaches. To this end, we have been isolating shark single domains to gain a greater understanding of their potential as therapeutic agents. Their unique shape, small size, inherent stability, and simple molecular architecture make them attractive candidates from a drug discovery perspective. Here we describe protocols to capture the immune repertoire of an immunized shark species and to build and select via phage-display target-specific IgNAR variable domains (VNARs).

  6. "Brazilian people" in the eyes of elites: repertoires and symbolic boundaries of inequality

    Directory of Open Access Journals (Sweden)

    Graziella Moraes Silva

    2015-04-01

    Full Text Available We analyze the cultural repertoires mobilized by elites to describe “Brazilian people.” We rely on survey and in-depth interview data to capture how political, bureaucratic and business elites in Brazil frame poverty and inequality. Our data suggest that elites acknowledge poverty as a structural problem for the State to solve, but remain skeptical on the odds of actual solutions, indicating fatalistic perceptions that categorize the Brazilian poor as unorganized, passive, ignorant, and irrational. Moreover, in their definition of the poor, elites draw a symbolic boundary, separating an active sector (which includes the elites and a passive one (the “people”. The paper also addresses the effects of such symbolic boundaries on the overall picture of Brazilian inequality.

  7. Using Existing Response Repertoires to Make Sense of Information System Implementation

    DEFF Research Database (Denmark)

    Jensen, Tina Blegind; Kjærgaard, Annemette Leonhardt

    2010-01-01

    The implementation of information systems (IS) in organizations often triggers new situations in which users experience a disruption of existing work patterns and routines. Sensemaking becomes central in making users’ meanings explicit, serving as a foundation for further actions and interactions...... with the new technology. The purpose of this paper is to study how users make sense of new technologies by building on existing response repertoires. Empirically, we present findings from a study of an Electronic Patient Record (EPR) system implementation in two Danish hospital wards. Our findings illustrate...... to existing literature by providing a detailed account of how users’ early sensemaking of a technology influences their subsequent actions and reactions towards it. Our findings support managers in understanding users’ perceptions of a new technology, helping them in planning and executing the implementation...

  8. Wnt repertoire and developmental expression patterns in the crustacean Thamnocephalus platyurus.

    Science.gov (United States)

    Constantinou, Savvas J; Pace, Ryan M; Stangl, A J; Nagy, Lisa M; Williams, Terri A

    2016-12-01

    Wnt genes are a family of conserved glycoprotein ligands that play a role in a wide variety of cell and developmental processes, from cell proliferation to axis elongation. There are 13 Wnt subfamilies found among metazoans. Eleven of these appear conserved in arthropods with a pattern of loss during evolution of as many as six subfamilies among hexapods. Here we report on Wnt genes in the branchiopod crustacean, Thamnocephalus platyurus, including the first documentation of the expression of the complete Wnt gene family in a crustacean. Our results suggest fewer Wnt genes were retained in Thamnocephalus than in the related crustacean, Daphnia, although the Thamnocephalus Wnt repertoire is larger than that found in insects. We also find an intriguing pattern of staggered expression of Wnts-an anterior-posterior stagger within the posterior growth zone and a dorsal-ventral stagger in the developing segments-suggesting a potential for subfunctionalization of Wnts in these regions. © 2016 Wiley Periodicals, Inc.

  9. Linguistic repertoires of interdisciplinarity in brazilian journals in the area of psychology

    Directory of Open Access Journals (Sweden)

    Mary Jane Paris Spink

    2014-12-01

    Full Text Available This paper is about manners in which linguistic repertoires of interdisciplinarity for dissemination of scientific knowledge are coordinated. It starts with a contextualization about interdisciplinarity and ways in which disciplines are organized for administrative purposes in Brazil. It seeks to answer the question: how these forms of ordering, controlling and coordinating interdisciplinary operate in the dissemination of scientific knowledge? The analysis of the ways of coordinating interdisciplinarity in scientific dissemination was based on the editorial proposals of journals classified as A1, A2 and B1 in the Qualis of the area of Psychology. The conclusion of this analysis is that scientific journals enact interdisciplinarity in different manners because they use various forms of association based on themes, related areas, and theories or theoretical frameworks. We conclude the analysis with a discussion of the implications of the various manners of coordinating knowledge for the dissemination of information for the public at large.

  10. Repertoire of gluten peptides active in celiac disease patients: perspectives for translational therapeutic applications.

    Science.gov (United States)

    Camarca, Alessandra; Del Mastro, Andrea; Gianfrani, Carmen

    2012-06-01

    Celiac disease is a common and lifelong food intolerance, affecting approximately 1% of the population. Because of a mechanism not completely understood, the ingestion of wheat gluten, and of homologue proteins of barley and rye, induces in genetically predisposed individuals pronounced inflammatory reactions mainly at the site of small intestine. Gluten, the triggering factor, is a complex protein mixture highly resistant to the gastrointestinal enzymatic proteolysis, and this results in the presence of large, and potentially immunogenic, peptides at the intestinal mucosa surface. During the last decade, several studies have defined gluten peptides able to stimulate adaptive T cells, of either CD4 or CD8 phenotype, and to activate innate (non T) immune cells. This review examines the complete repertoire of gluten peptides recognized by celiac T cells and discusses the several translational implications that the identification of these epitopes opens.

  11. Children show limited movement repertoire when learning a novel motor skill.

    Science.gov (United States)

    Lee, Mei-Hua; Farshchiansadegh, Ali; Ranganathan, Rajiv

    2017-09-27

    Examining age differences in motor learning using real-world tasks is often problematic due to task novelty and biomechanical confounds. Here, we investigated how children and adults acquire a novel motor skill in a virtual environment. Participants of three different age groups (9-year-olds, 12-year-olds, and adults) learned to use their upper body movements to control a cursor on a computer screen. Results showed that 9-year-old and 12-year-old children showed poorer ability to control the cursor at the end of practice. Critically, when we investigated the movement coordination, we found that the lower task performance of children was associated with limited exploration of their movement repertoire. These results reveal the critical role of motor exploration in understanding developmental differences in motor learning. © 2017 John Wiley & Sons Ltd.

  12. Using Existing Response Repertoires to Make Sense of Information System Implementation

    DEFF Research Database (Denmark)

    Jensen, Tina Blegind; Kjærgaard, Annemette Leonhardt

    2010-01-01

    : (1) how doctors’ and nurses’ existing routines are disrupted by the new technology, (2) how identity construction plays an important part in the users’ meaning construction process, and (3) how self-fulfilling prophecies are formed as a natural part of their sensemaking. The study contributes...... with the new technology. The purpose of this paper is to study how users make sense of new technologies by building on existing response repertoires. Empirically, we present findings from a study of an Electronic Patient Record (EPR) system implementation in two Danish hospital wards. Our findings illustrate...... to existing literature by providing a detailed account of how users’ early sensemaking of a technology influences their subsequent actions and reactions towards it. Our findings support managers in understanding users’ perceptions of a new technology, helping them in planning and executing the implementation...

  13. Profiling the repertoire of phenotypes influenced by environmental cues that occur during asexual reproduction.

    Science.gov (United States)

    Dombrovsky, Aviv; Arthaud, Laury; Ledger, Terence N; Tares, Sophie; Robichon, Alain

    2009-11-01

    The aphid Acyrthosiphon pisum population is composed of different morphs, such as winged and wingless parthenogens, males, and sexual females. The combined effect of reduced photoperiodicity and cold in fall triggers the apparition of sexual morphs. In contrast they reproduce asexually in spring and summer. In our current study, we provide evidence that clonal individuals display phenotypic variability within asexual morph categories. We describe that clones sharing the same morphological features, which arose from the same founder mother, constitute a repertoire of variants with distinct behavioral and physiological traits. Our results suggest that the prevailing environmental conditions influence the recruitment of adaptive phenotypes from a cohort of clonal individuals exhibiting considerable molecular diversity. However, we observed that the variability might be reduced or enhanced by external factors, but is never abolished in accordance with a model of stochastically produced phenotypes. This overall mechanism allows the renewal of colonies from a few adapted individuals that survive drastic episodic changes in a fluctuating environment.

  14. System Dynamics Modelling of the Processes Involving the Maintenance of the Naive T Cell Repertoire

    CERN Document Server

    Figueredo, Grazziela P; Whitbrook, Amanda

    2010-01-01

    The study of immune system aging, i.e. immunosenescence, is a relatively new research topic. It deals with understanding the processes of immunodegradation that indicate signs of functionality loss possibly leading to death. Even though it is not possible to prevent immunosenescence, there is great benefit in comprehending its causes, which may help to reverse some of the damage done and thus improve life expectancy. One of the main factors influencing the process of immunosenescence is the number and phenotypical variety of naive T cells in an individual. This work presents a review of immunosenescence, proposes system dynamics modelling of the processes involving the maintenance of the naive T cell repertoire and presents some preliminary results.

  15. Taste and odorant receptors of the coelacanth--a gene repertoire in transition.

    Science.gov (United States)

    Picone, Barbara; Hesse, Uljana; Panji, Sumir; Van Heusden, Peter; Jonas, Mario; Christoffels, Alan

    2014-09-01

    G-protein coupled chemosensory receptors (GPCR-CRs) aid in the perception of odors and tastes in vertebrates. So far, six GPCR-CR families have been identified that are conserved in most vertebrate species. Phylogenetic analyses indicate differing evolutionary dynamics between teleost fish and tetrapods. The coelacanth Latimeria chalumnae belongs to the lobe-finned fishes, which represent a phylogenetic link between these two groups. We searched the genome of L. chalumnae for GPCR-CRs and found that coelacanth taste receptors are more similar to those in tetrapods than in teleost fish: two coelacanth T1R2s co-segregate with the tetrapod T1R2s that recognize sweet substances, and our phylogenetic analyses indicate that the teleost T1R2s are closer related to T1R1s (umami taste receptors) than to tetrapod T1R2s. Furthermore, coelacanths are the first fish with a large repertoire of bitter taste receptors (58 T2Rs). Considering current knowledge on feeding habits of coelacanths the question arises if perception of bitter taste is the only function of these receptors. Similar to teleost fish, coelacanths have a variety of olfactory receptors (ORs) necessary for perception of water-soluble substances. However, they also have seven genes in the two tetrapod OR subfamilies predicted to recognize airborne molecules. The two coelacanth vomeronasal receptor families are larger than those in teleost fish, and similar to tetrapods and form V1R and V2R monophyletic clades. This may point to an advanced development of the vomeronasal organ as reported for lungfish. Our results show that the intermediate position of Latimeria in the phylogeny is reflected in its GPCR-CR repertoire.

  16. Tissue distribution and clonal diversity of the T and B cell repertoire in type 1 diabetes

    Science.gov (United States)

    Seay, Howard R.; Yusko, Erik; Rothweiler, Stephanie J.; Zhang, Lin; Posgai, Amanda L.; Campbell-Thompson, Martha; Emerson, Ryan O.; Kaddis, John S.; Ko, Dave; Nakayama, Maki; Smith, Mia J.; Cambier, John C.; Pugliese, Alberto; Atkinson, Mark A.; Robins, Harlan S.; Brusko, Todd M.

    2016-01-01

    The adaptive immune repertoire plays a critical role in type 1 diabetes (T1D) pathogenesis. However, efforts to characterize B cell and T cell receptor (TCR) profiles in T1D subjects have been largely limited to peripheral blood sampling and restricted to known antigens. To address this, we collected pancreatic draining lymph nodes (pLN), “irrelevant” nonpancreatic draining lymph nodes, peripheral blood mononuclear cells (PBMC), and splenocytes from T1D subjects (n = 18) and control donors (n = 9) as well as pancreatic islets from 1 T1D patient; from these tissues, we collected purified CD4+ conventional T cells (Tconv), CD4+ Treg, CD8+ T cells, and B cells. By conducting high-throughput immunosequencing of the TCR β chain (TRB) and B cell receptor (BCR) immunoglobulin heavy chain (IGH) on these samples, we sought to analyze the molecular signature of the lymphocyte populations within these tissues and of T1D. Ultimately, we observed a highly tissue-restricted CD4+ repertoire, while up to 24% of CD8+ clones were shared among tissues. We surveyed our data set for previously described proinsulin- and glutamic acid decarboxylase 65–reactive (GAD65-reactive) receptors, and interestingly, we observed a TRB with homology to a known GAD65-reactive TCR (clone GAD4.13) present in 7 T1D donors (38.9%), representing >25% of all productive TRB within Tconv isolated from the pLN of 1 T1D subject. These data demonstrate diverse receptor signatures at the nucleotide level and enriched autoreactive clones at the amino acid level, supporting the utility of coupling immunosequencing data with knowledge of characterized autoreactive receptors. PMID:27942583

  17. The heterogeneous allelic repertoire of human toll-like receptor (TLR genes.

    Directory of Open Access Journals (Sweden)

    Philippe Georgel

    Full Text Available Toll-Like Receptors (TLR are critical elements of the innate arm of the vertebrate immune system. They constitute a multigenic family of receptors which collectively bind a diverse array of--exogeneous as well as endogeneous--ligands. An exponential burst of knowledge has defined their biological role in fight against infections and generation/modulation of auto-immune disorders. Hence, they could at least be conceptually recognized--despite being structurally unrelated - as innate counterparts to Major Histocompatibility Complex (MHC molecules--equally recognizing antigenic ligands (albeit structurally more homogeneous i.e., peptides, again derived from self and/or non-self sources--preeminent this time in adaptive immunity. Our great disparities in face of infections and/or susceptibility to auto-immune diseases have provoked an intense search for genetic explanations, in part satisfied by the extraordinary MHC allelic repertoire. An equally in-depth and systematic analysis of TLR diversity is lacking despite numerous independent reports of a growing number of SNPs within these loci. The work described here aims at providing a preliminary picture of the allelic repertoire--and not purely SNPs--of all 10 human TLR coding sequences (with exception of TLR3 within a single cohort of up to 100 individuals. It appears from our work that TLR are unequally polymorphic: TLR2 (DNA alleles: 7/protein alleles: 3, 4 (4/3, 7 (6/3, 8 (9/2 and 9 (8/3 being comparatively least diverse whereas TLR1 (11/10, 5 (14/12, 6 (10/8 and 10 (15/10 show a substantial number of alleles. In addition to allelic assignment of a large number of SNPs, 10 new polymorphic positions were hereby identified. Hence this work depicts a first overview of the diversity of almost all human TLR genes, a prelude for large-scale population genetics as well as genetic association studies.

  18. The Full Globin Repertoire of Turtles Provides Insights into Vertebrate Globin Evolution and Functions.

    Science.gov (United States)

    Schwarze, Kim; Singh, Abhilasha; Burmester, Thorsten

    2015-06-15

    Globins are small heme proteins that play an important role in oxygen supply, but may also have other functions. Globins offer a unique opportunity to study the functional evolution of genes and proteins. We have characterized the globin repertoire of two different turtle species: the Chinese softshell turtle (Pelodiscus sinensis) and the western painted turtle (Chrysemys picta bellii). In the genomes of both species, we have identified eight distinct globin types: hemoglobin (Hb), myoglobin, neuroglobin, cytoglobin, globin E, globin X, globin Y, and androglobin. Therefore, along with the coelacanth, turtles are so far the only known vertebrates with a full globin repertoire. This fact allows for the first time a comparative analysis of the expression of all eight globins in a single species. Phylogenetic analysis showed an early divergence of neuroglobin and globin X before the radiation of vertebrates. Among the other globins, cytoglobin diverged first, and there is a close relationship between myoglobin and globin E; the position of globin Y is not resolved. The globin E gene was selectively lost in the green anole, and the genes coding for globin X and globin Y were deleted in chicken. Quantitative real-time reverse transcription polymerase chain reaction experiments revealed that myoglobin, neuroglobin, and globin E are highly expressed with tissue-specific patterns, which are in line with their roles in the oxidative metabolism of the striated muscles, the brain, and the retina, respectively. Histochemical analyses showed high levels of globin E in the pigment epithelium of the eye. Globin E probably has a myoglobin-like role in transporting O2 across the pigment epithelium to supply in the metabolically highly active retina.

  19. Expansion of the preimmune antibody repertoire by junctional diversity in Bos taurus.

    Directory of Open Access Journals (Sweden)

    Jenni Liljavirta

    Full Text Available Cattle have a limited range of immunoglobulin genes which are further diversified by antigen independent somatic hypermutation in fetuses. Junctional diversity generated during somatic recombination contributes to antibody diversity but its relative significance has not been comprehensively studied. We have investigated the importance of terminal deoxynucleotidyl transferase (TdT -mediated junctional diversity to the bovine immunoglobulin repertoire. We also searched for new bovine heavy chain diversity (IGHD genes as the information of the germline sequences is essential to define the junctional boundaries between gene segments. New heavy chain variable genes (IGHV were explored to address the gene usage in the fetal recombinations. Our bioinformatics search revealed five new IGHD genes, which included the longest IGHD reported so far, 154 bp. By genomic sequencing we found 26 new IGHV sequences that represent potentially new IGHV genes or allelic variants. Sequence analysis of immunoglobulin heavy chain cDNA libraries of fetal bone marrow, ileum and spleen showed 0 to 36 nontemplated N-nucleotide additions between variable, diversity and joining genes. A maximum of 8 N nucleotides were also identified in the light chains. The junctional base profile was biased towards A and T nucleotide additions (64% in heavy chain VD, 52% in heavy chain DJ and 61% in light chain VJ junctions in contrast to the high G/C content which is usually observed in mice. Sequence analysis also revealed extensive exonuclease activity, providing additional diversity. B-lymphocyte specific TdT expression was detected in bovine fetal bone marrow by reverse transcription-qPCR and immunofluorescence. These results suggest that TdT-mediated junctional diversity and exonuclease activity contribute significantly to the size of the cattle preimmune antibody repertoire already in the fetal period.

  20. The Full Globin Repertoire of Turtles Provides Insights into Vertebrate Globin Evolution and Functions

    Science.gov (United States)

    Schwarze, Kim; Singh, Abhilasha; Burmester, Thorsten

    2015-01-01

    Globins are small heme proteins that play an important role in oxygen supply, but may also have other functions. Globins offer a unique opportunity to study the functional evolution of genes and proteins. We have characterized the globin repertoire of two different turtle species: the Chinese softshell turtle (Pelodiscus sinensis) and the western painted turtle (Chrysemys picta bellii). In the genomes of both species, we have identified eight distinct globin types: hemoglobin (Hb), myoglobin, neuroglobin, cytoglobin, globin E, globin X, globin Y, and androglobin. Therefore, along with the coelacanth, turtles are so far the only known vertebrates with a full globin repertoire. This fact allows for the first time a comparative analysis of the expression of all eight globins in a single species. Phylogenetic analysis showed an early divergence of neuroglobin and globin X before the radiation of vertebrates. Among the other globins, cytoglobin diverged first, and there is a close relationship between myoglobin and globin E; the position of globin Y is not resolved. The globin E gene was selectively lost in the green anole, and the genes coding for globin X and globin Y were deleted in chicken. Quantitative real-time reverse transcription polymerase chain reaction experiments revealed that myoglobin, neuroglobin, and globin E are highly expressed with tissue-specific patterns, which are in line with their roles in the oxidative metabolism of the striated muscles, the brain, and the retina, respectively. Histochemical analyses showed high levels of globin E in the pigment epithelium of the eye. Globin E probably has a myoglobin-like role in transporting O2 across the pigment epithelium to supply in the metabolically highly active retina. PMID:26078264

  1. Contribution of V(H replacement products in mouse antibody repertoire.

    Directory of Open Access Journals (Sweden)

    Lin Huang

    Full Text Available VH replacement occurs through RAG-mediated recombination between the cryptic recombination signal sequence (cRSS near the 3' end of a rearranged VH gene and the 23-bp RSS from an upstream unrearranged VH gene. Due to the location of the cRSS, VH replacement leaves a short stretch of nucleotides from the previously rearranged VH gene at the newly formed V-D junction, which can be used as a marker to identify VH replacement products. To determine the contribution of VH replacement products to mouse antibody repertoire, we developed a Java-based VH Replacement Footprint Analyzer (VHRFA program and analyzed 17,179 mouse IgH gene sequences from the NCBI database to identify VH replacement products. The overall frequency of VH replacement products in these IgH genes is 5.29% based on the identification of pentameric VH replacement footprints at their V-D junctions. The identified VH replacement products are distributed similarly in IgH genes using most families of VH genes, although different families of VH genes are used differentially. The frequencies of VH replacement products are significantly elevated in IgH genes derived from several strains of autoimmune prone mice and in IgH genes encoding autoantibodies. Moreover, the identified VH replacement footprints in IgH genes from autoimmune prone mice or IgH genes encoding autoantibodies preferentially encode positively charged amino acids. These results revealed a significant contribution of VH replacement products to the diversification of antibody repertoire and potentially, to the generation of autoantibodies in mice.

  2. TCRep 3D: an automated in silico approach to study the structural properties of TCR repertoires.

    Directory of Open Access Journals (Sweden)

    Antoine Leimgruber

    Full Text Available TCRep 3D is an automated systematic approach for TCR-peptide-MHC class I structure prediction, based on homology and ab initio modeling. It has been considerably generalized from former studies to be applicable to large repertoires of TCR. First, the location of the complementary determining regions of the target sequences are automatically identified by a sequence alignment strategy against a database of TCR Vα and Vβ chains. A structure-based alignment ensures automated identification of CDR3 loops. The CDR are then modeled in the environment of the complex, in an ab initio approach based on a simulated annealing protocol. During this step, dihedral restraints are applied to drive the CDR1 and CDR2 loops towards their canonical conformations, described by Al-Lazikani et. al. We developed a new automated algorithm that determines additional restraints to iteratively converge towards TCR conformations making frequent hydrogen bonds with the pMHC. We demonstrated that our approach outperforms popular scoring methods (Anolea, Dope and Modeller in predicting relevant CDR conformations. Finally, this modeling approach has been successfully applied to experimentally determined sequences of TCR that recognize the NY-ESO-1 cancer testis antigen. This analysis revealed a mechanism of selection of TCR through the presence of a single conserved amino acid in all CDR3β sequences. The important structural modifications predicted in silico and the associated dramatic loss of experimental binding affinity upon mutation of this amino acid show the good correspondence between the predicted structures and their biological activities. To our knowledge, this is the first systematic approach that was developed for large TCR repertoire structural modeling.

  3. Massively parallel RNA sequencing identifies a complex immune gene repertoire in the lophotrochozoan Mytilus edulis.

    Directory of Open Access Journals (Sweden)

    Eva E R Philipp

    Full Text Available The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus.

  4. Statistical inference of the generation probability of T-cell receptors from sequence repertoires.

    Science.gov (United States)

    Murugan, Anand; Mora, Thierry; Walczak, Aleksandra M; Callan, Curtis G

    2012-10-02

    Stochastic rearrangement of germline V-, D-, and J-genes to create variable coding sequence for certain cell surface receptors is at the origin of immune system diversity. This process, known as "VDJ recombination", is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Because any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on nonproductive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our probabilistic model predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.

  5. Optical vortex array in spatially varying lattice

    CERN Document Server

    Kapoor, Amit; Senthilkumaran, P; Joseph, Joby

    2015-01-01

    We present an experimental method based on a modified multiple beam interference approach to generate an optical vortex array arranged in a spatially varying lattice. This method involves two steps which are: numerical synthesis of a consistent phase mask by using two-dimensional integrated phase gradient calculations and experimental implementation of produced phase mask by utilizing a phase only spatial light modulator in an optical 4f Fourier filtering setup. This method enables an independent variation of the orientation and period of the vortex lattice. As working examples, we provide the experimental demonstration of various spatially variant optical vortex lattices. We further confirm the existence of optical vortices by formation of fork fringes. Such lattices may find applications in size dependent trapping, sorting, manipulation and photonic crystals.

  6. Time varying arctic climate change amplification

    Energy Technology Data Exchange (ETDEWEB)

    Chylek, Petr [Los Alamos National Laboratory; Dubey, Manvendra K [Los Alamos National Laboratory; Lesins, Glen [DALLHOUSIE U; Wang, Muyin [NOAA/JISAO

    2009-01-01

    During the past 130 years the global mean surface air temperature has risen by about 0.75 K. Due to feedbacks -- including the snow/ice albedo feedback -- the warming in the Arctic is expected to proceed at a faster rate than the global average. Climate model simulations suggest that this Arctic amplification produces warming that is two to three times larger than the global mean. Understanding the Arctic amplification is essential for projections of future Arctic climate including sea ice extent and melting of the Greenland ice sheet. We use the temperature records from the Arctic stations to show that (a) the Arctic amplification is larger at latitudes above 700 N compared to those within 64-70oN belt, and that, surprisingly; (b) the ratio of the Arctic to global rate of temperature change is not constant but varies on the decadal timescale. This time dependence will affect future projections of climate changes in the Arctic.

  7. Local Rank Inference for Varying Coefficient Models.

    Science.gov (United States)

    Wang, Lan; Kai, Bo; Li, Runze

    2009-12-01

    By allowing the regression coefficients to change with certain covariates, the class of varying coefficient models offers a flexible approach to modeling nonlinearity and interactions between covariates. This paper proposes a novel estimation procedure for the varying coefficient models based on local ranks. The new procedure provides a highly efficient and robust alternative to the local linear least squares method, and can be conveniently implemented using existing R software package. Theoretical analysis and numerical simulations both reveal that the gain of the local rank estimator over the local linear least squares estimator, measured by the asymptotic mean squared error or the asymptotic mean integrated squared error, can be substantial. In the normal error case, the asymptotic relative efficiency for estimating both the coefficient functions and the derivative of the coefficient functions is above 96%; even in the worst case scenarios, the asymptotic relative efficiency has a lower bound 88.96% for estimating the coefficient functions, and a lower bound 89.91% for estimating their derivatives. The new estimator may achieve the nonparametric convergence rate even when the local linear least squares method fails due to infinite random error variance. We establish the large sample theory of the proposed procedure by utilizing results from generalized U-statistics, whose kernel function may depend on the sample size. We also extend a resampling approach, which perturbs the objective function repeatedly, to the generalized U-statistics setting; and demonstrate that it can accurately estimate the asymptotic covariance matrix.

  8. 基于时变市场分数的状态依赖自信的金融市场动态模型%A Model of Financial Market Trend with State-dependent Confidence Based on Time-varying Market Fraction

    Institute of Scientific and Technical Information of China (English)

    王婧

    2015-01-01

    在简单的金融市场动态模型中,风险证券的价格是由做市商依赖于异质交易者的超额需求来制定的. 异质交易者即基本面分析者与技术分析者,他们的需求依赖于未来价格的不同期望:技术分析者采用几何衰减过程形成期望,而基本面分析者被假定了解经济环境并形成相应的信念.本文通过引入时变市场分数,建立三维动力学模型,分析其稳定区域及产生的分支,并讨论主要参数对模型稳定性的影响,得到影响市场稳定性的因素.%In a simple model of financial market trend, the prices of risk securities are determined by market makers who depend on the excess demand of heterogeneous traders. The heterogeneous traders include basic situation analysts and technology analysts, whose de-mands depend on different expectations about future prices:the former are assumed to know the economic environment and form their be-liefs accordingly, while the latter form their expectations using geometric attenuation process. This paper introduced the time-varying market fraction, built the three-dimensional dynamical system, analyzed its stability region and branches, and discussed the influence of key parameters on the stability of the model, so as to obtain the influencing factors of market stability.

  9. Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge

    DEFF Research Database (Denmark)

    Christensen, Lars Harder; Holm, Jens-Christian; Lund, Gitte

    2008-01-01

    for the manifestation and severity of allergic symptoms. OBJECTIVE: We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation. METHODS: A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized...

  10. T-cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge

    NARCIS (Netherlands)

    Yurovsky, VV; Weersink, EJM; Meltzer, SS; Moore, WC; Postma, DS; Bleecker, ER; White, B

    1998-01-01

    T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell

  11. Incorporating Modern Piano Music into the Core Repertoire of Undergraduate Piano Majors: An Accessible and Manageable Syllabus

    Science.gov (United States)

    Edmonstone, Alastair Graham

    2012-01-01

    This dissertation will deal with the issue of incorporating modern piano music into the repertoire of piano students at the undergraduate degree level. For the purposes of this paper, it is assumed the students will be pursuing a major in music at a conservatory or university with piano as their instrument. In no way does this paper serve as an…

  12. Identity, small stories and interpretative repertoires in research interviews. An account of market researchers’ discursive positioning strategies

    Directory of Open Access Journals (Sweden)

    Cosmin Toth

    2014-12-01

    Full Text Available My main purpose in this paper is to illustrate how participants in a research interview occasioned conversation make use of two important discursive devices, namely: small stories and interpretative repertoires for positioning during interaction in order to foster certain situated identity claims. The premises I work with in this paper are that identity is a practiced situated accomplishment, that small stories are devices employed frequently for identity work that are no less important than extended autobiographical expositions, and that interpretative repertoires are practiced ways of speaking that allow participants to manage their positions in certain ways. Moreover, I will try to show that positioning by means of small stories and interpretative repertoires should be understood in direct relation with the identities and other membership categories made relevant by the interviewer. When participants’ positions are conflicting or miss-aligned, a more pronounced identity work is employed on the part of the interviewee, sustained by certain repertoires’ management strategies: alternation, nuancing, or rejecting certain repertoires.

  13. Classification of Captive North American River Otters (Lontra canadensis Vocal Repertoires: Individual Variations, and Age Class Comparisons

    Directory of Open Access Journals (Sweden)

    Carla Almonte

    2014-11-01

    Full Text Available This is the first study to examine in detail the vocal behaviors of North American river otters (Lontra canadensis, and the results suggest that river otters have complex vocal repertoires comprised of four distinct vocal types and seven sub-call types. The vocalizations and behaviors of ten captive North American river otter adults, one litter of newborn pups and one litter of pups at eight weeks old were recorded using a SONY Handheld DV camera and an infrared surveillance system. A quantitative analysis of 2726 calls on the adults and 299 calls for the pups was conducted for acoustic parameters that included frequencies, powers, and duration. Whine, chirp and chatter call types were the main vocal elements of the vocal repertoire and were present at birth. Pups vocals were structurally underdeveloped versions of the adult vocals and adults call types showed individual variations. This suggests that vocalizations are likely individually modified as pups enter adulthood. A unique whistle was present in newborn pup vocal repertoires but appeared to be reduced in the repertoire by eight weeks old. However, further research needs to be conducted to determine the function of the whistle.

  14. T-cell repertoire in the blood and lungs of atopic asthmatics before and after ragweed challenge

    NARCIS (Netherlands)

    Yurovsky, VV; Weersink, EJM; Meltzer, SS; Moore, WC; Postma, DS; Bleecker, ER; White, B

    T cells play a pivotal role in initiating and orchestrating allergic responses in asthma. The goal of this work was to learn whether ragweed challenge in the lungs alters the T-cell repertoire expressed in the blood and lungs of atopic asthmatics. Analyses of cell numbers, differentials, and T-cell

  15. Restricted IgA repertoire in both B-1 and B-2 cell-derived gut plasmablasts

    NARCIS (Netherlands)

    Stoel, M; Jiang, HQ; van Diemen, CC; Bun, JCAM; Dammers, PM; Thurnheer, MC; Kroese, FGM; Cebra, JJ; Bos, NA

    2005-01-01

    Mucosal IgA is the most abundantly produced Ig upon colonization of the intestinal tract with commensal organisms in the majority of mammals. The repertoire of these IgA molecules is still largely unknown; a large amount of the mucosal IgA cannot be shown to react with the inducing microorganisms.

  16. Incorporating Modern Piano Music into the Core Repertoire of Undergraduate Piano Majors: An Accessible and Manageable Syllabus

    Science.gov (United States)

    Edmonstone, Alastair Graham

    2012-01-01

    This dissertation will deal with the issue of incorporating modern piano music into the repertoire of piano students at the undergraduate degree level. For the purposes of this paper, it is assumed the students will be pursuing a major in music at a conservatory or university with piano as their instrument. In no way does this paper serve as an…

  17. Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response

    NARCIS (Netherlands)

    Tete, Sarah M.; Kipling, David; Westra, Johanna; de Haan, Aalzen; Bijl, Marc; Dunn-Walters, Deborah K.; Sahota, Surinder S.; Bos, Nicolaas A.

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examin

  18. Molecular Imprint of Exposure to Naturally Occurring Genetic Variants of Human Cytomegalovirus on the T cell Repertoire

    Science.gov (United States)

    Smith, Corey; Gras, Stephanie; Brennan, Rebekah M.; Bird, Nicola L.; Valkenburg, Sophie A.; Twist, Kelly-Anne; Burrows, Jacqueline M.; Miles, John J.; Chambers, Daniel; Bell, Scott; Campbell, Scott; Kedzierska, Katherine; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv

    2014-02-01

    Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

  19. Beyond the keyhole perspective: Quantitative and full repertoire imaging of T- and B-cell receptors using next generation sequencing

    NARCIS (Netherlands)

    P.L. Klarenbeek

    2013-01-01

    In this thesis we have demonstrated how next generation sequencing (NGS) can be used to screen the complete T-cell receptor and B-cell receptor (TCR and BCR) repertoires and identify, quantify and follow individual adaptive immune responses through time and place. As none of these objectives could b

  20. In vitro expansion of antigen-specific CD8(+) T cells distorts the T-cell repertoire.

    Science.gov (United States)

    Koning, Dan; Costa, Ana I; Hasrat, Raiza; Grady, Bart P X; Spijkers, Sanne; Nanlohy, Nening; Keşmir, Can; van Baarle, Debbie

    2014-03-01

    Short-term in vitro expansion of antigen-specific T cells is an appreciated assay for the analysis of small memory T-cell populations. However, how well short-term expanded T cells represent the direct ex vivo situation remains to be elucidated. In this study we compared the clonality of Epstein-Barr virus (EBV) and cytomegalovirus (CMV)-specific CD8(+) T cells directly ex vivo and after in vitro stimulation with antigen. Our data show that the antigen-specific T cell repertoire significantly alters after in vitro culture. Clear shifts in clonotype hierarchy were observed, with the most dominant ex vivo clonotype decreasing after stimulation at the expense of several previously subdominant clonotypes. Notably, these alterations were more pronounced in polyclonal T-cell populations compared to mono- or oligoclonal repertoires. Furthermore, TCR diversity significantly increased after culture with antigen. These results suggest that the T-cell repertoire is highly subjective to variation after in vitro stimulation with antigen. Hence, although short-term expansion of T cells provides a simple and efficient tool to examine antigen-specific immune responses, caution is required if T-cell populations are expanded prior to detailed, clonotypic analyses or other repertoire-based investigations.

  1. Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response

    NARCIS (Netherlands)

    Tete, Sarah M.; Kipling, David; Westra, Johanna; de Haan, Aalzen; Bijl, Marc; Dunn-Walters, Deborah K.; Sahota, Surinder S.; Bos, Nicolaas A.

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examin

  2. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with Wiskott Aldrich syndrome

    Directory of Open Access Journals (Sweden)

    Amy E O'Connell

    2014-07-01

    Full Text Available The Wiskott Aldrich syndrome (WAS is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein (WASp, leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR, BCR. We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing, the T cell receptor beta (TRB and B cell immunoglobulin heavy chain (IGH repertoires of 8 patients with WAS and 6 controls were sequenced. Clonal expansions were identified within memory CD4+ cells, as well as in total, naïve and memory CD8+ cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using next generation sequencing.

  3. Next Generation Sequencing Reveals Skewing of the T and B Cell Receptor Repertoires in Patients with Wiskott–Aldrich Syndrome

    Science.gov (United States)

    O’Connell, Amy E.; Volpi, Stefano; Dobbs, Kerry; Fiorini, Claudia; Tsitsikov, Erdyni; de Boer, Helen; Barlan, Isil B.; Despotovic, Jenny M.; Espinosa-Rosales, Francisco J.; Hanson, I. Celine; Kanariou, Maria G.; Martínez-Beckerat, Roxana; Mayorga-Sirera, Alvaro; Mejia-Carvajal, Carmen; Radwan, Nesrine; Weiss, Aaron R.; Pai, Sung-Yun; Lee, Yu Nee; Notarangelo, Luigi D.

    2014-01-01

    The Wiskott–Aldrich syndrome (WAS) is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein, leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR and BCR). We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing (NGS), the T cell receptor β and B cell immunoglobulin heavy chain (IGH) repertoires of eight patients with WAS and six controls were sequenced. Clonal expansions were identified within memory CD4+ cells as well as in total, naïve and memory CD8+ cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using NGS. PMID:25101082

  4. Gait phase varies over velocities.

    Science.gov (United States)

    Liu, Yancheng; Lu, Kun; Yan, Songhua; Sun, Ming; Lester, D Kevin; Zhang, Kuan

    2014-02-01

    We sought to characterize the percent (PT) of the phases of a gait cycle (GC) as velocity changes to establish norms for pathological gait characteristics with higher resolution technology. Ninety five healthy subjects (49 males and 46 females with age 34.9 ± 11.8 yrs, body weight 64.0 ± 11.7 kg and BMI 23.5 ± 3.6) were enrolled and walked comfortably on a 10-m walkway at self-selected slower, normal, and faster velocities. Walking was recorded with a high speed camera (250 frames per second) and the eight phases of a GC were determined by examination of individual frames for each subject. The correlation coefficients between the mean PT of the phases of the three velocities gaits and PT defined by previous publications were all greater than 0.99. The correlation coefficient between velocity and PT of gait phases is -0.83 for loading response (LR), -0.75 for mid stance (MSt), and -0.84 for pre-swing (PSw). While the PT of the phases of three velocities from this study are highly correlated with PT described by Dr. Jacquenlin Perry decades ago, actual PT of each phase varied amongst these individuals with the largest coefficient variation of 24.31% for IC with slower velocity. From slower to faster walk, the mean PT of MSt diminished from 35.30% to 25.33%. High resolution recording revealed ambiguity of some gait phase definitions, and these data may benefit GC characterization of normal and pathological gait in clinical practice. The study results indicate that one should consider individual variations and walking velocity when evaluating gaits of subjects using standard gait phase classification.

  5. Audio Effects Based on Biorthogonal Time-Varying Frequency Warping

    Directory of Open Access Journals (Sweden)

    Cavaliere Sergio

    2001-01-01

    Full Text Available We illustrate the mathematical background and musical use of a class of audio effects based on frequency warping. These effects alter the frequency content of a signal via spectral mapping. They can be implemented in dispersive tapped delay lines based on a chain of all-pass filters. In a homogeneous line with first-order all-pass sections, the signal formed by the output samples at a given time is related to the input via the Laguerre transform. However, most musical signals require a time-varying frequency modification in order to be properly processed. Vibrato in musical instruments or voice intonation in the case of vocal sounds may be modeled as small and slow pitch variations. Simulation of these effects requires techniques for time-varying pitch and/or brightness modification that are very useful for sound processing. The basis for time-varying frequency warping is a time-varying version of the Laguerre transformation. The corresponding implementation structure is obtained as a dispersive tapped delay line, where each of the frequency dependent delay element has its own phase response. Thus, time-varying warping results in a space-varying, inhomogeneous, propagation structure. We show that time-varying frequency warping is associated to an expansion over biorthogonal sets generalizing the discrete Laguerre basis. Slow time-varying characteristics lead to slowly varying parameter sequences. The corresponding sound transformation does not suffer from discontinuities typical of delay lines based on unit delays.

  6. A new mechanism shapes the naïve CD8(+) T cell repertoire: the selection for full diversity.

    Science.gov (United States)

    Gonçalves, Pedro; Ferrarini, Marco; Molina-Paris, Carmen; Lythe, Grant; Vasseur, Florence; Lim, Annik; Rocha, Benedita; Azogui, Orly

    2017-05-01

    During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clonal sizes. Indeed with these approaches, identical TCRs may correspond to different cells expressing the same receptor, or to several amplicons from the same T cell. We here overcame this limitation by evaluating TCRB expression in individual naïve CD8(+) T cells. Of the 2269 Tcrb sequences we obtained from 13 mice, 99% were unique. Mathematical analysis of the data showed that the average number of naïve peripheral CD8(+) T cells expressing the same TCRB is 1.1 cell. Since TCRA co-expression studies could only increase repertoire diversity, these results reveal that the number of naïve T cells with unique TCRs approaches the number of naïve cells. Since thymocytes undergo multiple rounds of divisions after TCRB rearrangement and 3-5% of thymocytes survive thymic selection events the number of cells expressing the same TCRB was expected to be much higher. Thus, these results suggest a new repertoire selection mechanism, which strongly selects for full TCRB diversity.

  7. The relationship between syllable repertoire similarity and pairing success in a passerine bird species with complex song.

    Science.gov (United States)

    Garamszegi, László Zsolt; Zsebok, Sándor; Török, János

    2012-02-21

    Repertoire size, i.e. the number of unique song elements that an individual possesses, is thought to be an important target of female preference. However, the use of repertoire size reflects how researchers work with complex songs; while it does not necessary describe biological functions, as listeners of song may also rely on song composition. Specific syllables may have coherent consequences for mate attraction because they are costly to produce, mediate syllable sharing or indicate the dialect of origin. We tested for the relationship between song composition and pairing success in the collared flycatcher (Ficedula albicollis). We applied a tree-clustering method to hierarchically classify males based on the degree of repertoire overlap, and then used a phylogenetic approach to assess the degree by which pairing speed matches the hierarchically structured song data. We found that males using similar syllables also find a breeding partner at a similar speed. Partitioning the variance components of pairing speed, we detected that the consequences of particular syllables for mating are repeatable across males. When assessing the role of repertoire similarity in mediating direct syllable sharing, we derived a positive relationship between the physical distance between pairs of males and their repertoire overlap implying that neighboring males avoid copying each other's song. Finally, we were unable to demonstrate that syllables related to higher mating success are more common in the population, which would support mechanisms based on female preference for local songs. Our results imply that individual-specific song organization may be relevant for sexual selection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Analysis of the Repertoire Features of TCR Beta Chain CDR3 in Human by High-Throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Xianliang Hou

    2016-07-01

    Full Text Available Background/Aims: To ward off a wide variety of pathogens, the human adaptive immune system harbors a vast array of T-cell receptors, collectively referred to as the TCR repertoire. Assessment of the repertoire features of TCR is vital for us to deeper understand of immune behaviour and immune response. Methods: In this study, we used a combination of multiplex-PCR, Illumina sequencing and IMGT (ImMunoGeneTics/HighV-QUEST for a standardized analysis of the repertoire features of TCR beta chain in the blood of healthy individuals, including the repertoire features of public TCR complementarity-determining regions (CDR3 sequences, highly expanded clones, long TCR CDR3 sequences. Results: We found that public CDR3 sequences and high-frequency sequences had the same characteristics, both of them had fewer nucleotide additions and shorter CDR3 length, which were closer to the germline sequence. Moreover, our studies provided evidence that public amino acid sequences are produced by multiple nucleotide sequences. Notably, there was skewed VDJ segment usage in long CDR3 sequences, the expression levels of 10 TRβV segments, 7 TRβJ segments and 2 TRβD segments were significantly different in the long CDR3 sequences compared to the short CDR3 sequences. Moreover, we identified that extensive N additions and increase of D gene usage contributing to TCR CDR3 length, and observed there was distinct usage frequency of amino acids in long CDR3 sequences compared to the short CDR3 sequences. Conclusions: Some repertoire features could be observed in the public sequences, highly abundance clones, and long TCR CDR3 sequences, which might be helpful for further study of immune behavior and immune response.

  9. TRGV and TRDV repertoire distribution and clonality of T cells from umbilical cord blood.

    Science.gov (United States)

    Li, Yangqiu; Chen, Shaohua; Yang, Lijian; Li, Bo; Chan, John Yeuk-Hon; Cai, Dongqing

    2009-01-01

    Umbilical cord blood (CB) has been used as a valuable source of hematopoietic stem cells for allogeneic transplantation, specific CTL response and immunotherapy for decades. We previously analyzed the distribution and clonality of T-cell receptor alpha and beta variable region (TRAV) and (TRBV) of the subfamily T cell receptors in T cells from umbilical cord blood. Recent data indicated that gammadelta(+) T cells may play an important role in mediating the graft versus leukemia effect after stem cells transplantation and in anti-cancer response. In order to further characterize the repertoire of CB T-cells, the frequency of alphabeta(+) and gammadelta(+) T cells were examined in CB by FACS. The CDR3 size of 4 TRGV and 8 TRDV subfamily genes were analyzed in mononuclear cells (MCs) from 16 CB samples, using RT-PCR and genescan technique. To determine the expression level of TRGV subfamily genes, we performed quantitative analysis of TRGVI-III subfamilies by real-time PCR. Low percentage of CD3(+)TCRgammadelta(+) cells was observed in CB. The frequency of expression in TRGVI, TRGVII and TRGVIII in CBMCs was 93.75%, 81.25% and 56.25%, respectively. The mean value of the number of expressed TRDV subfamilies in CBMCs is higher than that from adult peripheral blood (PB) group. The frequently expressed members in CB were TRDV1 (100%), TRDV2 (93.75%), TRDV8 (93.75%) and TRDV3 (81.25%), respectively. The frequencies of TRDV5 and TRDV8 in CBMCs were significantly higher than those from PBMCs. Most of the PCR products of TRGV and TRDV subfamilies from 10 CB samples displayed polyclonal rearrangement pattern, whereas one or two PCR products from 6 CB samples showed oligoclonality or biclonality. In contrast, PCR products from 9 of 10 adult healthy controls contained at least an oligoclonal peak in different TRGV or TRDV subfamilies respectively. The pattern of TRGV subfamily expression level in CBMCs was TRGVI>TRGVIII>TRGVII, and in contrast, TRGVII>TRGVI>TRGVIII was found in

  10. Difficulties when assessing birdsong learning programmes under field conditions: a re-evaluation of song repertoire flexibility in the great tit.

    Directory of Open Access Journals (Sweden)

    Hector F Rivera-Gutierrez

    Full Text Available There is a remarkable diversity of song-learning strategies in songbirds. Establishing whether a species is closed- or open-ended is important to be able to interpret functional and evolutionary consequences of variation in repertoire size. Most of our knowledge regarding the timing of vocal learning is based on laboratory studies, despite the fact that these may not always replicate the complex ecological and social interactions experienced by birds in the wild. Given that field studies cannot provide the experimental control of laboratory studies, it may not be surprising that species such as the great tit that were initially assumed to be closed-ended learners have later been suggested to be open-ended learners. By using an established colour-ringed population, by following a standardized recording protocol, and by taking into account the species' song ecology (using only recordings obtained during peak of singing at dawn, we replicated two previous studies to assess song repertoire learning and flexibility in adult wild great tits elicited by social interactions. First, we performed a playback experiment to test repertoire plasticity elicited by novel versus own songs. Additionally, in a longitudinal study, we followed 30 males in two consecutive years and analysed whether new neighbours influenced any change in the repertoire. Contrary to the previous studies, song repertoire size and composition were found to be highly repeatable both between years and after confrontation with a novel song. Our results suggest that great tits are closed-ended learners and that their song repertoire probably does not change during adulthood. Methodological differences that may have led to an underestimation of the repertoires or population differences may explain the discrepancy in results with previous studies. We argue that a rigorous and standardized assessment of the repertoire is essential when studying age- or playback-induced changes in repertoire

  11. Comparative Genomics Analysis of a New Exiguobacterium Strain from Salar de Huasco Reveals a Repertoire of Stress-Related Genes and Arsenic Resistance

    Science.gov (United States)

    Castro-Severyn, Juan; Remonsellez, Francisco; Valenzuela, Sandro L.; Salinas, Cesar; Fortt, Jonathan; Aguilar, Pablo; Pardo-Esté, Coral; Dorador, Cristina; Quatrini, Raquel; Molina, Franck; Aguayo, Daniel; Castro-Nallar, Eduardo; Saavedra, Claudia P.

    2017-01-01

    The Atacama Desert hosts diverse ecosystems including salt flats and shallow Andean lakes. Several heavy metals are found in the Atacama Desert, and microorganisms growing in this environment show varying levels of resistance/tolerance to copper, tellurium, and arsenic, among others. Herein, we report the genome sequence and comparative genomic analysis of a new Exiguobacterium strain, sp. SH31, isolated from an altiplanic shallow athalassohaline lake. Exiguobacterium sp. SH31 belongs to the phylogenetic Group II and its closest relative is Exiguobacterium sp. S17, isolated from the Argentinian Altiplano (95% average nucleotide identity). Strain SH31 encodes a wide repertoire of proteins required for cadmium, copper, mercury, tellurium, chromium, and arsenic resistance. Of the 34 Exiguobacterium genomes that were inspected, only isolates SH31 and S17 encode the arsenic efflux pump Acr3. Strain SH31 was able to grow in up to 10 mM arsenite and 100 mM arsenate, indicating that it is arsenic resistant. Further, expression of the ars operon and acr3 was strongly induced in response to both toxics, suggesting that the arsenic efflux pump Acr3 mediates arsenic resistance in Exiguobacterium sp. SH31. PMID:28377753

  12. Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species

    Directory of Open Access Journals (Sweden)

    Okamura Hiroaki

    2009-09-01

    Full Text Available Abstract Background In mammals, pheromones play an important role in social and innate reproductive behavior within species. In rodents, vomeronasal receptor type 1 (V1R, which is specifically expressed in the vomeronasal organ, is thought to detect pheromones. The V1R gene repertoire differs dramatically between mammalian species, and the presence of species-specific V1R subfamilies in mouse and rat suggests that V1R plays a profound role in species-specific recognition of pheromones. In ruminants, however, the molecular mechanism(s for pheromone perception is not well understood. Interestingly, goat male pheromone, which can induce out-of-season ovulation in anestrous females, causes the same pheromone response in sheep, and vice versa, suggesting that there may be mechanisms for detecting "inter-species" pheromones among ruminant species. Results We isolated 23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow V1R genes in the cow genome database. We found that all of the goat and sheep V1R genes have orthologs in their cross-species counterparts among these three ruminant species and that the sequence identity of V1R orthologous pairs among these ruminants is much higher than that of mouse-rat V1R orthologous pairs. Furthermore, all goat V1Rs examined thus far are expressed not only in the vomeronasal organ but also in the main olfactory epithelium. Conclusion Our results suggest that, compared with rodents, the repertoire of orthologous V1R genes is remarkably conserved among the ruminants cow, sheep and goat. We predict that these orthologous V1Rs can detect the same or closely related chemical compound(s within each orthologous set/pair. Furthermore, all identified goat V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium, suggesting that V1R-mediated ligand information can be detected and processed by both the main and accessory olfactory systems. The fact that ruminant and rodent V1Rs

  13. The motor repertoire in 3- to 5-month old infants with Down syndrome.

    Science.gov (United States)

    Herrero, Dafne; Einspieler, Christa; Panvequio Aizawa, Carolina Y; Mutlu, Akmer; Yang, Hong; Nogolová, Alice; Pansy, Jasmin; Nielsen-Saines, Karin; Marschik, Peter B

    2017-08-01

    Even though Down syndrome is the most common chromosomal cause of intellectual disability, studies on early development are scarce. To describe movements and postures in 3- to 5-month-old infants with Down syndrome and assess the relation between pre- and perinatal risk factors and the eventual motor performance. Exploratory study; 47 infants with Down syndrome (26 males, 27 infants born preterm, 22 infants with congenital heart disease) were videoed at 10-19 weeks post-term (median=14 weeks). We assessed their Motor Optimality Score (MOS) based on postures and movements (including fidgety movements) and compared it to that of 47 infants later diagnosed with cerebral palsy and 47 infants with a normal neurological outcome, matched for gestational and recording ages. The MOS (median=13, range 10-28) was significantly lower than in infants with a normal neurological outcome (median=26), but higher than in infants later diagnosed with cerebral palsy (median=6). Fourteen infants with Down syndrome showed normal fidgety movements, 13 no fidgety movements, and 20 exaggerated, too fast or too slow fidgety movements. A lack of movements to the midline and several atypical postures were observed. Neither preterm birth nor congenital heart disease was related to aberrant fidgety movements or reduced MOS. The heterogeneity in fidgety movements and MOS add to an understanding of the large variability of the early phenotype of Down syndrome. Studies on the predictive values of the early spontaneous motor repertoire, especially for the cognitive outcome, are warranted. The significance of this exploratory study lies in its minute description of the motor repertoire of infants with Down syndrome aged 3-5 months. Thirty percent of infants with Down syndrome showed age-specific normal fidgety movements. The rate of abnormal fidgety movements (large amplitude, high/slow speed) or a lack of fidgety movements was exceedingly high. The motor optimality score of infants with Down

  14. General in vitro method to analyze the interactions of synthetic polymers with human antibody repertoires.

    Science.gov (United States)

    Soshee, Anandakumar; Zürcher, Stefan; Spencer, Nicholas D; Halperin, Avraham; Nizak, Clément

    2014-01-13

    Recent reports on the hitherto underestimated antigenicity of poly(ethylene glycol) (PEG), which is widely used for pharmaceutical applications, highlight the need for efficient testing of polymer antigenicity and for a better understanding of its molecular origins. With this goal in mind, we have used the phage-display technique to screen large, recombinant antibody repertoires of human origin in vitro for antibodies that bind poly(vinylpyrrolidone) (PVP). PVP is a neutral synthetic polymer of industrial and clinical interest that is also a well-known model antigen in animal studies, thus allowing the comparison of in vitro and in vivo responses. We have identified 44 distinct antibodies that bind specifically to PVP. Competitive binding assays show that the PVP-antibody binding constant is proportional to the polymerization degree of PVP and that specific binding is detected down to the vinylpyrrolidone (VP) monomer level. Statistical analysis of anti-PVP antibody sequences identifies an amino-acid motif that is shared by many phage-display-selected anti-PVP antibodies that are similar to a previously described natural anti-PVP antibody. This suggests a role for this motif in specific antibody/PVP interactions. Interestingly, sequence analysis also suggests that only a single antibody chain containing this shared motif is responsible for antibody binding to PVP, as confirmed upon systematic deletion of either antibody chain for 90% of selected anti-PVP antibodies. Overall, a large number of antibodies in the human repertoires we have screened bind specifically to PVP through a small number of shared amino acid motifs, and preliminary comparison points to significant correlations between the sequences of phage-display-selected anti-PVP antibodies and their natural counterparts isolated from immunized mice in previous studies. This study pioneers the use of antibody phage-display to explore the antigenicity of biotechnologically relevant polymers. It also paves the

  15. BRILIA: Integrated Tool for High-Throughput Annotation and Lineage Tree Assembly of B-Cell Repertoires

    Science.gov (United States)

    Lee, Donald W.; Khavrutskii, Ilja V.; Wallqvist, Anders; Bavari, Sina; Cooper, Christopher L.; Chaudhury, Sidhartha

    2017-01-01

    The somatic diversity of antigen-recognizing B-cell receptors (BCRs) arises from Variable (V), Diversity (D), and Joining (J) (VDJ) recombination and somatic hypermutation (SHM) during B-cell development and affinity maturation. The VDJ junction of the BCR heavy chain forms the highly variable complementarity determining region 3 (CDR3), which plays a critical role in antigen specificity and binding affinity. Tracking the selection and mutation of the CDR3 can be useful in characterizing humoral responses to infection and vaccination. Although tens to hundreds of thousands of unique BCR genes within an expressed B-cell repertoire can now be resolved with high-throughput sequencing, tracking SHMs is still challenging because existing annotation methods are often limited by poor annotation coverage, inconsistent SHM identification across the VDJ junction, or lack of B-cell lineage data. Here, we present B-cell repertoire inductive lineage and immunosequence annotator (BRILIA), an algorithm that leverages repertoire-wide sequencing data to globally improve the VDJ annotation coverage, lineage tree assembly, and SHM identification. On benchmark tests against simulated human and mouse BCR repertoires, BRILIA correctly annotated germline and clonally expanded sequences with 94 and 70% accuracy, respectively, and it has a 90% SHM-positive prediction rate in the CDR3 of heavily mutated sequences; these are substantial improvements over existing methods. We used BRILIA to process BCR sequences obtained from splenic germinal center B cells extracted from C57BL/6 mice. BRILIA returned robust B-cell lineage trees and yielded SHM patterns that are consistent across the VDJ junction and agree with known biological mechanisms of SHM. By contrast, existing BCR annotation tools, which do not account for repertoire-wide clonal relationships, systematically underestimated both the size of clonally related B-cell clusters and yielded inconsistent SHM frequencies. We demonstrate

  16. A Minimum Epitope Overlap between Infections Strongly Narrows the Emerging T Cell Repertoire

    Directory of Open Access Journals (Sweden)

    Susanne G. Oberle

    2016-10-01

    Full Text Available Many infections are caused by pathogens that are similar, but not identical, to previously encountered viruses, bacteria, or vaccines. In such re-infections, pathogens introduce known antigens, which are recognized by memory T cells and new antigens that activate naive T cells. How preexisting memory T cells impact the repertoire of T cells responding to new antigens is still largely unknown. We demonstrate that even a minimum epitope overlap between infections strongly increases the activation threshold and narrows the diversity of T cells recruited in response to new antigens. Thus, minimal cross-reactivity between infections can significantly impact the outcome of a subsequent immune response. Interestingly, we found that non-transferrable memory T cells are most effective in raising the activation threshold. Our findings have implications for designing vaccines and suggest that vaccines meant to target low-affinity T cells are less effective when they contain a strong CD8 T cell epitope that has previously been encountered.

  17. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2016-01-01

    BACKGROUND The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. METHODS The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. RESULTS Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. CONCLUSIONS Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

  18. Genome-wide characterisation of the binding repertoire of small molecule drugs

    Directory of Open Access Journals (Sweden)

    Makowski Lee

    2003-11-01

    Full Text Available Abstract Most, if not all, drugs interact with multiple proteins. One or more of these interactions are responsible for carrying out the primary therapeutic effects of the drug. Others are involved in the transport or metabolic processing of the drug or in the mediation of side effects. Still others may be responsible for activities that correspond to alternate therapeutic applications. The potential clinical impact of a drug and its cost of development are affected by the sum of all these interactions. The drug development process includes the identification and characterisation of a drug's clinically relevant interactions. This characterisation is presently accomplished by a combination of experimental laboratory techniques and clinical trials, with increasing numbers of patient participants. Efficient methods for the identification of all the molecular targets of a drug prior to clinical trials could greatly expedite the drug development process. Combinatorial peptide and cDNA phage display have the potential for achieving a complete characterisation of the binding repertoire of a small molecule. This paper will discuss the current state of phage display technology, as applied to the identification of novel receptors for small molecules, using a successful application with the drug Taxol™ as an example of the technical and theoretical benefits and pitfalls of this method.

  19. The application of real-time PCR to the analysis of T cell repertoires.

    Science.gov (United States)

    Wettstein, Peter; Strausbauch, Michael; Therneau, Terry; Borson, Nancy

    2008-12-01

    The diversity of T-cell populations is determined by the spectrum of antigen-specific T-cell receptors (TCRs) that are heterodimers of alpha and beta subunits encoded by rearranged combinations of variable (AV and BV), joining (AJ and BJ), and constant region genes (AC and BC). We have developed a novel approach for analysis of beta transcript diversity in mice with a real-time PCR-based method that uses a matrix of BV- and BJ-specific primers to amplify 240 distinct BV-BJ combinations. Defined endpoints (Ct values) and dissociation curves are generated for each BV-BJ combination and the Ct values are consolidated in a matrix that characterizes the beta transcript diversity of each RNA sample. Relative diversities of BV-BJ combinations in individual RNA samples are further described by estimates of scaled entropy. A skin allograft system was used to demonstrate that dissection of repertoires into 240 BV-BJ combinations increases efficiency of identifying and sequencing beta transcripts that are overrepresented at inflammatory sites. These BV-BJ matrices should generate greater investigation in laboratory and clinical settings due to increased throughput, resolution and identification of overrepresented TCR transcripts.

  20. Inhibition of RORγT Skews TCRα Gene Rearrangement and Limits T Cell Repertoire Diversity

    Directory of Open Access Journals (Sweden)

    Yanxia Guo

    2016-12-01

    Full Text Available Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP thymocytes. While RORγ antagonists are currently being developed to treat autoimmunity, it remains unclear how RORγT inhibition may impact thymocyte development. In this study, we show that in addition to regulating DP thymocytes survival, RORγT also controls genes that regulate thymocyte migration, proliferation, and T cell receptor (TCRα selection. Strikingly, pharmacological inhibition of RORγ skews TCRα gene rearrangement, limits T cell repertoire diversity, and inhibits development of autoimmune encephalomyelitis. Thus, targeting RORγT not only inhibits Th17 cell development and function but also fundamentally alters thymic-emigrant recognition of self and foreign antigens. The analysis of RORγ inhibitors has allowed us to gain a broader perspective of the diverse function of RORγT and its impact on T cell biology.

  1. Precarious Voices? Types of “Political Citizens” and Repertoires of Action among European Youth

    Directory of Open Access Journals (Sweden)

    Lara Monticelli

    2017-01-01

    Full Text Available In spite of cross national differences, one of the most relevant concerns for young European people nowadays, is represented by job insecurity. In this contribution, the authors aim to shed light on the triggering role of job precariousness and unemployment on individual repertoires of political actions among young people in three European cities (Lyon in France, Turin in Italy, Cologne in Germany. Theo-retically, the paper addresses the existing limitations in the literature on precarious workers’ political par-ticipation by proposing a new comprehensive framework which includes a broad set of actions, including institutionalized and non-institutionalized forms of political action (e.g. petitions, public demonstrations, disruptive actions. Empirically, a quantitative descriptive technique - Latent Class Cluster Analysis (LCCA- is deployed allowing to take into account different variables (e.g. socio-demographic conditions, educa-tional attainment, age, employment status and political beliefs to portray, for each city under analysis and for each “mode” of participation, a set of ideal-typical individual profiles

  2. Discovery of diverse and functional antibodies from large human repertoire antibody libraries.

    Science.gov (United States)

    Schwimmer, Lauren J; Huang, Betty; Giang, Hoa; Cotter, Robyn L; Chemla-Vogel, David S; Dy, Francis V; Tam, Eric M; Zhang, Fangjiu; Toy, Pamela; Bohmann, David J; Watson, Susan R; Beaber, John W; Reddy, Nithin; Kuan, Hua-Feng; Bedinger, Daniel H; Rondon, Isaac J

    2013-05-31

    Phage display antibody libraries have a proven track record for the discovery of therapeutic human antibodies, increasing the demand for large and diverse phage antibody libraries for the discovery of new therapeutics. We have constructed naïve antibody phage display libraries in both Fab and scFv formats, with each library having more than 250 billion clones that encompass the human antibody repertoire. These libraries show high fidelity in open reading frame and expression percentages, and their V-gene family distribution, VH-CDR3 length and amino acid usage mirror the natural diversity of human antibodies. Both the Fab and scFv libraries show robust sequence diversity in target-specific binders and differential V-gene usage for each target tested, supporting the use of libraries that utilize multiple display formats and V-gene utilization to maximize antibody-binding diversity. For each of the targets, clones with picomolar affinities were identified from at least one of the libraries and for the two targets assessed for activity, functional antibodies were identified from both libraries.

  3. The human and mouse repertoire of the adhesion family of G-protein-coupled receptors.

    Science.gov (United States)

    Bjarnadóttir, Thóra K; Fredriksson, Robert; Höglund, Pär J; Gloriam, David E; Lagerström, Malin C; Schiöth, Helgi B

    2004-07-01

    The adhesion G-protein-coupled receptors (GPCRs) (also termed LN-7TM or EGF-7TM receptors) are membrane-bound proteins with long N-termini containing multiple domains. Here, 2 new human adhesion-GPCRs, termed GPR133 and GPR144, have been found by searches done in the human genome databases. Both GPR133 and GPR144 have a GPS domain in their N-termini, while GPR144 also has a pentraxin domain. The phylogenetic analyses of the 2 new human receptors show that they group together without close relationship to the other adhesion-GPCRs. In addition to the human genes, mouse orthologues to those 2 and 15 other mouse orthologues to human were identified (GPR110, GPR111, GPR112, GPR113, GPR114, GPR115, GPR116, GPR123, GPR124, GPR125, GPR126, GPR128, LEC1, LEC2, and LEC3). Currently the total number of human adhesion-GPCRs is 33. The mouse and human sequences show a clear one-to-one relationship, with the exception of EMR2 and EMR3, which do not seem to have orthologues in mouse. EST expression charts for the entire repertoire of adhesion-GPCRs in human and mouse were established. Over 1600 ESTs were found for these receptors, showing widespread distribution in both central and peripheral tissues. The expression patterns are highly variable between different receptors, indicating that they participate in a number of physiological processes. Copyright 2003 Elsevier Inc.

  4. High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia.

    Science.gov (United States)

    Ramesh, Manish; Simchoni, Noa; Hamm, David; Cunningham-Rundles, Charlotte

    2015-12-01

    To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.

  5. Sequence Analysis of Bitter Taste Receptor Gene Repertoires in Different Ruminant Species.

    Directory of Open Access Journals (Sweden)

    Ana Monteiro Ferreira

    Full Text Available Bitter taste has been extensively studied in mammalian species and is associated with sensitivity to toxins and with food choices that avoid dangerous substances in the diet. At the molecular level, bitter compounds are sensed by bitter taste receptor proteins (T2R present at the surface of taste receptor cells in the gustatory papillae. Our work aims at exploring the phylogenetic relationships of T2R gene sequences within different ruminant species. To accomplish this goal, we gathered a collection of ruminant species with different feeding behaviors and for which no genome data is available: American bison, chamois, elk, European bison, fallow deer, goat, moose, mouflon, muskox, red deer, reindeer and white tailed deer. The herbivores chosen for this study belong to different taxonomic families and habitats, and hence, exhibit distinct foraging behaviors and diet preferences. We describe the first partial repertoires of T2R gene sequences for these species obtained by direct sequencing. We then consider the homology and evolutionary history of these receptors within this ruminant group, and whether it relates to feeding type classification, using MEGA software. Our results suggest that phylogenetic proximity of T2R genes corresponds more to the traditional taxonomic groups of the species rather than reflecting a categorization by feeding strategy.

  6. A Comparison of Epitope Repertoires Associated with Myasthenia Gravis in Humans and Nonhuman Hosts

    Directory of Open Access Journals (Sweden)

    Kerrie Vaughan

    2012-01-01

    Full Text Available Here we analyzed the molecular targets associated with myasthenia gravis (MG immune responses, enabled by an immune epitope database (IEDB inventory of approximately 600 MG-related epitopes derived from 175 references. The vast majority of epitopes were derived from the α-subunit of human AChR suggesting that other MG-associated autoantigens should be investigated further. Human α-AChR was mostly characterized in humans, whereas reactivity primarily to T. californica AChR was examined in animal models. While the fine specificity of T-cell response was similar in the two systems, substantial antibody reactivity to the C-terminus was detected in the nonhuman system, but not in humans. Further analysis showed that the reactivity of nonhuman hosts to the C-terminus was eliminated when data were restricted to hosts tested in the context of autoimmune disease (spontaneous or induced, demonstrating that the epitopes recognized in humans and animals were shared when disease was present. Finally, we provided data subsets relevant to particular applications, including those associated with HLA typing or restriction, sets of epitopes recognized by monoclonal antibodies, and epitopes associated with modulation of immunity or disease. In conclusion, this analysis highlights gaps, differences, and similarities in the epitope repertoires of humans and animal models.

  7. Extremely Long-Range Chromatin Loops Link Topological Domains to Facilitate a Diverse Antibody Repertoire

    Directory of Open Access Journals (Sweden)

    Lindsey Montefiori

    2016-02-01

    Full Text Available Early B cell development is characterized by large-scale Igh locus contraction prior to V(DJ recombination to facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates locus contraction remains unclear. We have combined high-resolution chromosome conformation capture (3C techniques with 3D DNA FISH to identify three conserved topological subdomains. Each of these topological folds encompasses a major VH gene family that become juxtaposed in pro-B cells via megabase-scale chromatin looping. The transcription factor Pax5 organizes the subdomain that spans the VHJ558 gene family. In its absence, the J558 VH genes fail to associate with the proximal VH genes, thereby providing a plausible explanation for reduced VHJ558 gene rearrangements in Pax5-deficient pro-B cells. We propose that Igh locus contraction is the cumulative effect of several independently controlled chromatin subdomains that provide the structural infrastructure to coordinate optimal antigen receptor assembly.

  8. MicroRNA repertoire for functional genome research in tilapia identified by deep sequencing.

    Science.gov (United States)

    Yan, Biao; Wang, Zhen-Hua; Zhu, Chang-Dong; Guo, Jin-Tao; Zhao, Jin-Liang

    2014-08-01

    The Nile tilapia (Oreochromis niloticus; Cichlidae) is an economically important species in aquaculture and occupies a prominent position in the aquaculture industry. MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression involved in diverse biological and metabolic processes. To increase the repertoire of miRNAs characterized in tilapia, we used the Illumina/Solexa sequencing technology to sequence a small RNA library using pooled RNA sample isolated from the different developmental stages of tilapia. Bioinformatic analyses suggest that 197 conserved and 27 novel miRNAs are expressed in tilapia. Sequence alignments indicate that all tested miRNAs and miRNAs* are highly conserved across many species. In addition, we characterized the tissue expression patterns of five miRNAs using real-time quantitative PCR. We found that miR-1/206, miR-7/9, and miR-122 is abundantly expressed in muscle, brain, and liver, respectively, implying a potential role in the regulation of tissue differentiation or the maintenance of tissue identity. Overall, our results expand the number of tilapia miRNAs, and the discovery of miRNAs in tilapia genome contributes to a better understanding the role of miRNAs in regulating diverse biological processes.

  9. Expansion of the protein repertoire in newly explored environments: human gut microbiome specific protein families.

    Directory of Open Access Journals (Sweden)

    Kyle Ellrott

    2010-06-01

    Full Text Available The microbes that inhabit particular environments must be able to perform molecular functions that provide them with a competitive advantage to thrive in those environments. As most molecular functions are performed by proteins and are conserved between related proteins, we can expect that organisms successful in a given environmental niche would contain protein families that are specific for functions that are important in that environment. For instance, the human gut is rich in polysaccharides from the diet or secreted by the host, and is dominated by Bacteroides, whose genomes contain highly expanded repertoire of protein families involved in carbohydrate metabolism. To identify other protein families that are specific to this environment, we investigated the distribution of protein families in the currently available human gut genomic and metagenomic data. Using an automated procedure, we identified a group of protein families strongly overrepresented in the human gut. These not only include many families described previously but also, interestingly, a large group of previously unrecognized protein families, which suggests that we still have much to discover about this environment. The identification and analysis of these families could provide us with new information about an environment critical to our health and well being.

  10. Noise during rest enables the exploration of the brain's dynamic repertoire.

    Directory of Open Access Journals (Sweden)

    Anandamohan Ghosh

    2008-10-01

    Full Text Available Traditionally brain function is studied through measuring physiological responses in controlled sensory, motor, and cognitive paradigms. However, even at rest, in the absence of overt goal-directed behavior, collections of cortical regions consistently show temporally coherent activity. In humans, these resting state networks have been shown to greatly overlap with functional architectures present during consciously directed activity, which motivates the interpretation of rest activity as day dreaming, free association, stream of consciousness, and inner rehearsal. In monkeys, it has been shown though that similar coherent fluctuations are present during deep anesthesia when there is no consciousness. Here, we show that comparable resting state networks emerge from a stability analysis of the network dynamics using biologically realistic primate brain connectivity, although anatomical information alone does not identify the network. We specifically demonstrate that noise and time delays via propagation along connecting fibres are essential for the emergence of the coherent fluctuations of the default network. The spatiotemporal network dynamics evolves on multiple temporal scales and displays the intermittent neuroelectric oscillations in the fast frequency regimes, 1-100 Hz, commonly observed in electroencephalographic and magnetoencephalographic recordings, as well as the hemodynamic oscillations in the ultraslow regimes, <0.1 Hz, observed in functional magnetic resonance imaging. The combination of anatomical structure and time delays creates a space-time structure in which the neural noise enables the brain to explore various functional configurations representing its dynamic repertoire.

  11. Microbial culturomics unravels the halophilic microbiota repertoire of table salt: description of Gracilibacillus massiliensis sp. nov.

    Directory of Open Access Journals (Sweden)

    Awa Diop

    2016-10-01

    Full Text Available Background: Microbial culturomics represents an ongoing revolution in the characterization of environmental and human microbiome. Methods: By using three media containing high salt concentration (100, 150, and 200 g/L, the halophilic microbial culturome of a commercial table salt was determined. Results: Eighteen species belonging to the Terrabacteria group were isolated including eight moderate halophilic and 10 halotolerant bacteria. Gracilibacillus massiliensis sp. nov., type strain Awa-1T (=CSUR P1441=DSM 29726, is a moderately halophilic gram-positive, non-spore-forming rod, and is motile by using a flagellum. Strain Awa-1T shows catalase activity but no oxidase activity. It is not only an aerobic bacterium but also able to grow in anaerobic and microaerophilic atmospheres. The draft genome of G. massiliensis is 4,207,226 bp long, composed of 13 scaffolds with 36.05% of G+C content. It contains 3,908 genes (3,839 protein-coding and 69 RNA genes. At least 1,983 (52% orthologous proteins were not shared with the closest phylogenetic species. Hundred twenty-six genes (3.3% were identified as ORFans. Conclusions: Microbial culturomics can dramatically improve the characterization of the food and environmental microbiota repertoire, deciphering new bacterial species and new genes. Further studies will clarify the geographic specificity and the putative role of these new microbes and their related functional genetic content in environment, health, and disease.

  12. NEO-FASCIST MOBILIZATION IN CONTEMPORARY ITALY. IDEOLOGY AND REPERTOIRE OF ACTION OF CASAPOUND ITALIA

    Directory of Open Access Journals (Sweden)

    Caterina Froio

    2015-03-01

    Full Text Available Although the most researched extreme right actors take the form of political parties, social movements research has recently started analysing extreme right organizations that go beyond ordinary politics and that take the form of 'groupuscular’ organizations. However, most existing contributions rely on secondary data and focus mainly on public networks and online activism of extreme right actors and their strategies of action. Very few ethnographic studies of extreme right social movements exist with the result that we still need a deeper understanding of their off-line mobilization, ideological discourse and militancy and how these in turn interact with the choice of specific repertoires of action. In this framework, the aim of this paper is to present the findings of a research project that explored dynamics of militant participation and forms of activism promoted by a neo-fascist organization: CasaPound Italia. Combining ethnography, semi-structured interviews and content analysis, we analyse the communicative, organizational and ideological nature of CasaPound’s political engagement, and its heterogeneous, unconventional melange of political references, communication strategies and choices of protest action.

  13. Narrative Inquiry for Science Education: Teachers' repertoire-making in the case of environmental curriculum

    Science.gov (United States)

    Hwang, Seyoung

    2011-04-01

    This paper considers how the school science curriculum can be conceptualised in order to address the contingent and complex nature of environmental and sustainability-related knowledge and understanding. A special concern lies in the development of research perspectives and tools for investigating ways, in which teachers are faced with complex and various situations in the sense-making of science-related issues, and subsequent pedagogic issues. Based on an empirical examination of Korean teachers' sense-making of their curricular practice, the paper develops a narrative approach to teachers' perspectives and knowledge by considering the value of stories as sense-making tools for reflective questioning of what is worth teaching, how and why. By employing the idea of 'repertoire', the study regards teachers' stories about their environment-related personal and teaching experiences as offering angles with which to understand teachers' motivation and reflection in curricular development and implementation. Furthermore, three empirical cases present ways in which the nature of knowledge and understanding is recognised and potentially integrated into pedagogies through teachers' narratives. Finally, the paper argues for the need to reconsider the role of the science teacher in addressing environmental and sustainability-related issues, in ways that facilitate teachers' reflexive interpretation of meanings in cultural texts and the construction of pedagogic text.

  14. Quantitative assessment of T-cell repertoire recovery after hematopoietic stem cell transplantation

    Science.gov (United States)

    van Heijst, Jeroen W J; Ceberio, Izaskun; Lipuma, Lauren B; Samilo, Dane W; Wasilewski, Gloria D; Gonzales, Anne Marie R; Nieves, Jimmy L; van den Brink, Marcel R M; Perales, Miguel A; Pamer, Eric G

    2012-01-01

    Delayed T-cell recovery and restricted T-cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity following allo-HSCT. Here we combined 5′-RACE PCR with deep sequencing, to quantify TCR diversity in 28 allo-HSCT recipients using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that the frequency of individual TCRs was accurately determined. After 6 months, cord blood graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T-cell-depleted peripheral blood stem cell grafts had a 28-fold and 14-fold lower CD4+ and CD8+ T-cell diversity, respectively. After 12 months, these deficiencies had improved for the CD4+, but not the CD8+ T-cell compartment. Overall, this method provides unprecedented views of T-cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse. PMID:23435170

  15. Time-Varying FOPDT System Identification with Unknown Disturbance Input

    DEFF Research Database (Denmark)

    Sun, Zhen; Yang, Zhenyu

    2012-01-01

    The Time-Varying First Order Plus Dead Time (TV-FOPDT) model is an extension of the conventional FOPDT by allowing the system parameters, which are primarily defined on the transfer function description, i.e., the DC-gain, time constant and time delay, to be time dependent. The TV-FOPDT identific...

  16. The repertoire of heavy chain immunoglobulin genes in B‑cell chronic lymphocytic leukemia in Russia and Belarus

    Directory of Open Access Journals (Sweden)

    B. V. Biderman

    2012-01-01

    Full Text Available Mutation status of the heavy chain variable region genes has long been known as an important factor in long‑term prognosis in B‑cell chronic lymphocytic leukemia (B‑CLL. A more detailed study of the gene sequences of immunoglobulin heavy chain (IgVH led to the discovery of stereotyped antigen receptors (SAR — receptors that have the same set of VH‑, D‑ and JH‑genes used. Cells with SARs have been found almost in a quarter of all B‑CLL cases. This phenomenon is not observed in other lymphatic tumors. In our study, we confirmed and extended the basic observations concerning the repertoire of IgVH in B‑CLL. Differences in the B‑CLL IgVH gene repertoirs between Russia, Вelarus and other countries are also analysed and discussed.

  17. The repertoire of heavy chain immunoglobulin genes in B‑cell chronic lymphocytic leukemia in Russia and Belarus

    Directory of Open Access Journals (Sweden)

    B. V. Biderman

    2014-07-01

    Full Text Available Mutation status of the heavy chain variable region genes has long been known as an important factor in long‑term prognosis in B‑cell chronic lymphocytic leukemia (B‑CLL. A more detailed study of the gene sequences of immunoglobulin heavy chain (IgVH led to the discovery of stereotyped antigen receptors (SAR — receptors that have the same set of VH‑, D‑ and JH‑genes used. Cells with SARs have been found almost in a quarter of all B‑CLL cases. This phenomenon is not observed in other lymphatic tumors. In our study, we confirmed and extended the basic observations concerning the repertoire of IgVH in B‑CLL. Differences in the B‑CLL IgVH gene repertoirs between Russia, Вelarus and other countries are also analysed and discussed.

  18. Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline Ig gene repertoire.

    Science.gov (United States)

    Scheepers, Cathrine; Shrestha, Ram K; Lambson, Bronwen E; Jackson, Katherine J L; Wright, Imogen A; Naicker, Dshanta; Goosen, Mark; Berrie, Leigh; Ismail, Arshad; Garrett, Nigel; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Moore, Penny L; Travers, Simon A; Morris, Lynn

    2015-05-01

    The human Ig repertoire is vast, producing billions of unique Abs from a limited number of germline Ig genes. The IgH V region (IGHV) is central to Ag binding and consists of 48 functional genes. In this study, we analyzed whether HIV-1-infected individuals who develop broadly neutralizing Abs show a distinctive germline IGHV profile. Using both 454 and Illumina technologies, we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing Abs. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of mAbs isolated from seven of these women, as well as previously isolated broadly neutralizing Abs from other donors, provided evidence that at least eight novel or non-IMGT alleles contributed to functional Abs. Importantly, we found that, despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing Abs, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing Abs. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive Ig database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing Ab development in HIV-1 infection, with positive implications for HIV vaccine design.

  19. PD-1 identifies the patient-specific CD8⁺ tumor-reactive repertoire infiltrating human tumors.

    Science.gov (United States)

    Gros, Alena; Robbins, Paul F; Yao, Xin; Li, Yong F; Turcotte, Simon; Tran, Eric; Wunderlich, John R; Mixon, Arnold; Farid, Shawn; Dudley, Mark E; Hanada, Ken-Ichi; Almeida, Jorge R; Darko, Sam; Douek, Daniel C; Yang, James C; Rosenberg, Steven A

    2014-05-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8⁺ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8⁺ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8⁺ lymphocytes. In all 6 tumors studied, expression of the inhibitory receptors programmed cell death 1 (PD-1; also known as CD279), lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell immunoglobulin and mucin domain 3 (TIM-3) on CD8⁺ TILs identified the autologous tumor-reactive repertoire, including mutated neoantigen-specific CD8⁺ lymphocytes, whereas only a fraction of the tumor-reactive population expressed the costimulatory receptor 4-1BB (also known as CD137). TCRβ deep sequencing revealed oligoclonal expansion of specific TCRβ clonotypes in CD8⁺PD-1⁺ compared with CD8⁺PD-1- TIL populations. Furthermore, the most highly expanded TCRβ clonotypes in the CD8⁺ and the CD8⁺PD-1⁺ populations recognized the autologous tumor and included clonotypes targeting mutated antigens. Thus, in addition to the well-documented negative regulatory role of PD-1 in T cells, our findings demonstrate that PD-1 expression on CD8⁺ TILs also accurately identifies the repertoire of clonally expanded tumor-reactive cells and reveal a dual importance of PD-1 expression in the tumor microenvironment.

  20. Modelling tourists arrival using time varying parameter

    Science.gov (United States)

    Suciptawati, P.; Sukarsa, K. G.; Kencana, Eka N.

    2017-06-01

    The importance of tourism and its related sectors to support economic development and poverty reduction in many countries increase researchers’ attentions to study and model tourists’ arrival. This work is aimed to demonstrate time varying parameter (TVP) technique to model the arrival of Korean’s tourists to Bali. The number of Korean tourists whom visiting Bali for period January 2010 to December 2015 were used to model the number of Korean’s tourists to Bali (KOR) as dependent variable. The predictors are the exchange rate of Won to IDR (WON), the inflation rate in Korea (INFKR), and the inflation rate in Indonesia (INFID). Observing tourists visit to Bali tend to fluctuate by their nationality, then the model was built by applying TVP and its parameters were approximated using Kalman Filter algorithm. The results showed all of predictor variables (WON, INFKR, INFID) significantly affect KOR. For in-sample and out-of-sample forecast with ARIMA’s forecasted values for the predictors, TVP model gave mean absolute percentage error (MAPE) as much as 11.24 percent and 12.86 percent, respectively.

  1. A Generalized Theory of Varying Alpha

    CERN Document Server

    Barrow, John D

    2011-01-01

    In this paper, we formulate a generalization of the simple Bekenstein-Sandvik-Barrow-Magueijo (BSBM) theory of varying alpha by allowing the coupling constant, \\omega, for the corresponding scalar field \\psi\\ to depend on \\psi. We focus on the situation where \\omega\\ is exponential in \\psi\\ and find the late-time behaviours that occur in matter-dominated and dark-energy dominated cosmologies. We also consider the situation when the background expansion scale factor of the universe evolves in proportion to an arbitrary power of the cosmic time. We find the conditions under which the fine structure `constant' increases with time, as in the BSBM theory, and establish a cosmic no-hair behaviour for accelerating universes. We also find the conditions under which the fine structure `constant' can decrease with time and compare the whole family of models with astronomical data from quasar absorption spectra. Finally, we show that spatial variations on sub-horizon scales can dominate over the cosmological time evolut...

  2. Combination of two anti-CD5 monoclonal antibodies synergistically induces complement-dependent cytotoxicity of chronic lymphocytic leukaemia cells

    DEFF Research Database (Denmark)

    Klitgaard, Josephine L; Koefoed, Klaus; Geisler, Christian

    2013-01-01

    secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of mAbs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) both as single m...

  3. Repertoires of emotion regulation: A person-centered approach to assessing emotion regulation strategies and links to psychopathology.

    Science.gov (United States)

    Dixon-Gordon, Katherine L; Aldao, Amelia; De Los Reyes, Andres

    2015-01-01

    Despite growing research on emotion regulation (ER) strategies and psychopathology, research has primarily focused on identifying one-to-one associations between ER strategies and symptoms. Thus, little is known about how patterns in the repertoires of ER strategies are associated with different mental disorders. We utilised latent class analysis to identify distinct repertoires of ER strategies, and their links with various psychopathology domains (i.e., anxiety, depression, disordered eating, borderline personality). Participants (N = 531) reported on their use of seven ER strategies in six recalled stressful contexts, as well as on their symptoms of psychopathology. We identified five classes of ER strategies: Low Regulators (n = 168), High Regulators (n = 140), Adaptive Regulators (n = 99), Worriers/Ruminators (n = 96) and Avoiders (n = 28). Generally, High Regulators and Worriers/Ruminators endorsed greater levels of psychopathology, relative to Low and Adaptive Regulators. Our findings underscore the importance of characterising the dynamics of ER repertoires when seeking to understand links between ER strategies and psychopathology.

  4. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Chang

    Full Text Available Human induced pluripotent stem cells (hiPSCs have enormous potential for the treatment of inherited and acquired disorders. Recently, antigen-specific T lymphocytes derived from hiPSCs have been reported. However, T lymphocyte populations with broad T cell receptor (TCR diversity have not been generated. We report that hiPSCs derived from skin biopsy are capable of producing T lymphocyte populations with a broad TCR repertoire. In vitro T cell differentiation follows a similar developmental program as observed in vivo, indicated by sequential expression of CD7, intracellular CD3 and surface CD3. The γδ TCR locus is rearranged first and is followed by rearrangement of the αβ locus. Both γδ and αβ T cells display a diverse TCR repertoire. Upon activation, the cells express CD25, CD69, cytokines (TNF-α, IFN-γ, IL-2 and cytolytic proteins (Perforin and Granzyme-B. These results suggest that most, if not all, mechanisms required to generate functional T cells with a broad TCR repertoire are intact in our in vitro differentiation protocol. These data provide a foundation for production of patient-specific T cells for the treatment of acquired or inherited immune disorders and for cancer immunotherapy.

  5. Regulation of TCR delta and alpha repertoires by local and long-distance control of variable gene segment chromatin structure.

    Science.gov (United States)

    Hawwari, Abbas; Krangel, Michael S

    2005-08-15

    Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4- CD8- (double negative [DN]) and CD4+ CD8+ (double positive [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex regulation. Only a small subset of approximately 100 variable gene segments contributes substantially to the adult TCRdelta repertoire. Moreover, although most contribute to the TCRalpha repertoire, variable gene segments that are Jalpha proximal are preferentially used during primary Tcra recombination. We investigate the role of local chromatin accessibility in determining the developmental pattern of TcraTcrd locus variable gene segment recombination. We find variable gene segments to be heterogeneous with respect to acetylation of histones H3 and H4. Those that dominate the adult TCRdelta repertoire are hyperacetylated in DN thymocytes, independent of their position in the locus. Moreover, proximal variable gene segments show dramatic increases in histone acetylation and germline transcription in DP thymocytes, a result of super long-distance regulation by the Tcra enhancer. Our results imply that differences in chromatin accessibility contribute to biases in TcraTcrd locus variable gene segment recombination in DN and DP thymocytes and extend the distance over which the Tcra enhancer can regulate chromatin structure to a remarkable 525 kb.

  6. From everyday communicative figurations to rigorous audience news repertoires: A mixed method approach to cross-media news consumption

    Directory of Open Access Journals (Sweden)

    Christian Kobbernagel

    2016-06-01

    Full Text Available In the last couple of decades there has been an unprecedented explosion of news media platforms and formats, as a succession of digital and social media have joined the ranks of legacy media. We live in a ‘hybrid media system’ (Chadwick, 2013, in which people build their cross-media news repertoires from the ensemble of old and new media available. This article presents an innovative mixed-method approach with considerable explanatory power to the exploration of patterns of news media consumption. This approach tailors Q-methodology in the direction of a qualitative study of news consumption, in which a card sorting exercise serves to translate the participants’ news media preferences into a form that enables the researcher to undertake a rigorous factor-analytical construction of their news consumption repertoires. This interpretive, factor-analytical procedure, which results in the building of six audience news repertoires in Denmark, also preserves the qualitative thickness of the participants’ verbal accounts of the communicative figurations of their day-in-the-life with the news media.

  7. The effects of a partitioned var gene repertoire of Plasmodium falciparum on antigenic diversity and the acquisition of clinical immunity

    Directory of Open Access Journals (Sweden)

    Arinaminpathy Nimalan

    2008-01-01

    Full Text Available Abstract Background The human malaria parasite Plasmodium falciparum exploits antigenic diversity and within-host antigenic variation to evade the host's immune system. Of particular importance are the highly polymorphic var genes that encode the family of cell surface antigens PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1. It has recently been shown that in spite of their extreme diversity, however, these genes fall into distinct groups according to chromosomal location or sequence similarity, and that recombination may be confined within these groups. Methods This study presents a mathematical analysis of how recombination hierarchies affect diversity, and, by using simple stochastic simulations, investigates how intra- and inter-genic diversity influence the rate at which individuals acquire clinical immunity. Results The analysis demonstrates that the partitioning of the var gene repertoire has a limiting effect on the total diversity attainable through recombination and that the limiting effect is strongly influenced by the respective sizes of each of the partitions. Furthermore, by associating expression of one of the groups with severe malaria it is demonstrated how a small number of infections can be sufficient to protect against disease despite a seemingly limitless number of possible non-identical repertoires. Conclusion Recombination hierarchies within the var gene repertoire of P. falciparum have a severe effect on strain diversity and the process of acquiring immunity against clinical malaria. Future studies will show how the existence of these recombining groups can offer an evolutionary advantage in spite of their restriction on diversity.

  8. Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice.

    Science.gov (United States)

    Candéias, Serge M; Mika, Justyna; Finnon, Paul; Verbiest, Tom; Finnon, Rosemary; Brown, Natalie; Bouffler, Simon; Polanska, Joanna; Badie, Christophe

    2017-06-30

    While the biological effects of high-dose-ionizing radiation on human health are well characterized, the consequences of low-dose radiation exposure remain poorly defined, even though they are of major importance for radiological protection. Lymphocytes are very radiosensitive, and radiation-induced health effects may result from immune cell loss and/or immune system impairment. To decipher the mechanisms of effects of low doses, we analyzed the modulation of the T-cell receptor gene repertoire in mice exposed to a single low (0.1 Gy) or high (1 Gy) dose of radiation. High-throughput T-cell receptor gene profiling was used to visualize T-lymphocyte dynamics over time in control and irradiated mice. Radiation exposure induces "aging-like" effects on the T-cell receptor gene repertoire, detectable as early as 1 month post-exposure and for at least 6 months. Surprisingly, these effects are more pronounced in animals exposed to 0.1 Gy than to 1 Gy, where partial correction occurs over time. Importantly, we found that low-dose radiation effects are partially due to the hematopoietic stem cell impairment. Collectively, our findings show that acute low-dose radiation exposure specifically results in long-term alterations of the T-lymphocyte repertoire.

  9. Highly diverse TCRα chain repertoire of pre-immune CD8⁺ T cells reveals new insights in gene recombination.

    Science.gov (United States)

    Genolet, Raphael; Stevenson, Brian J; Farinelli, Laurent; Osterås, Magne; Luescher, Immanuel F

    2012-04-04

    Although the T-cell receptor αδ (TCRαδ) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCRα chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By sequencing tens of millions of TCRα chain transcripts from naive mouse CD8(+) T cells, we observed a hugely diverse repertoire, comprising nearly all possible TRAV-TRAJ combinations. Our findings are not compatible with sequential coordinate gene recombination, but rather with a model in which contraction and DNA looping in the TCRαδ locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCRα chain repertoire necessitates deletion of failed attempts by thymic-positive selection and is essential for the formation of highly diverse TCRαβ repertoires, capable of providing good protective immunity.

  10. Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

    Science.gov (United States)

    Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

    2014-05-01

    Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation.

  11. Innate-like γδ T cell responses to mycobacterium Bacille Calmette-Guerin using the public Vγ2 repertoire in Macaca fascicularis

    Science.gov (United States)

    Cairo, Cristiana; Hebbeler, Andrew M; Propp, Nadia; Bryant, Joseph L; Colizzi, Vittorio; Pauza, C. David

    2010-01-01

    The Vγ2Vδ2 T cell subset responds to Bacille Calmette-Guerin (BCG) immunization in macaques and may be a component of protective immunity against tuberculosis. We characterized the effects of BCG on the Vγ2Vδ2 T cell receptor repertoire by comparing the starting population of Vγ2 chains in cynomolgus macaques with the repertoire found after priming or booster immunization with BCG. The starting repertoire was dominated by public Vγ2 chain sequences that were found repeatedly among unrelated animals. Primary exposure to BCG triggered expansion of cells expressing public Vγ2 chains and booster immunization was often associated with contraction of these same subsets. Thus, BCG-reactive Vγ2 chains were present at high frequency in the repertoire of mycobacteria-naïve macaques and they comprised the major response to primary or booster immunization. Normal selection processes that created the naïve Vγ2 repertoire in macaques, also encoded the capacity for rapid responses to mycobacteria. The unusual composition of a normal Vγ2 repertoire helps to explain the powerful γδ T cell responses to BCG immunization. PMID:17292671

  12. Innate-like gammadelta T cell responses to mycobacterium Bacille Calmette-Guerin using the public V gamma 2 repertoire in Macaca fascicularis.

    Science.gov (United States)

    Cairo, Cristiana; Hebbeler, Andrew M; Propp, Nadia; Bryant, Joseph L; Colizzi, Vittorio; Pauza, C David

    2007-07-01

    The V gamma 2 V delta 2 T cell subset responds to Bacille Calmette-Guerin (BCG) immunization in macaques and may be a component of protective immunity against tuberculosis. We characterized the effects of BCG on the V gamma 2 V delta 2 T cell receptor repertoire by comparing the starting population of V gamma 2 chains in cynomolgus macaques with the repertoire found after priming or booster immunization with BCG. The starting repertoire was dominated by public V gamma 2 chain sequences that were found repeatedly among unrelated animals. Primary exposure to BCG triggered expansion of cells expressing public V gamma 2 chains and booster immunization was often associated with contraction of these same subsets. Thus, BCG-reactive V gamma 2 chains were present at high frequency in the repertoire of mycobacteria-naïve macaques and they comprised the major response to primary or booster immunization. Normal selection processes that created the naïve V gamma 2 repertoire in macaques, also encoded the capacity for rapid responses to mycobacteria. The unusual composition of a normal V gamma 2 repertoire helps to explain the powerful gammadelta T cell responses to BCG immunization.

  13. Comparative analyses of developmental transcription factor repertoires in sponges reveal unexpected complexity of the earliest animals.

    Science.gov (United States)

    Fortunato, Sofia A V; Adamski, Marcin; Adamska, Maja

    2015-12-01

    Developmental transcription factors (DTFs) control development of animals by affecting expression of target genes, some of which are transcription factors themselves. In bilaterians and cnidarians, conserved DTFs are involved in homologous processes such as gastrulation or specification of neurons. The genome of Amphimedon queenslandica, the first sponge to be sequenced, revealed that only a fraction of these conserved DTF families are present in demosponges. This finding was in line with the view that morphological complexity in the animal lineage correlates with developmental toolkit complexity. However, as the phylum Porifera is very diverse, Amphimedon's genome may not be representative of all sponges. The recently sequenced genomes of calcareous sponges Sycon ciliatum and Leucosolenia complicata allowed investigations of DTFs in a sponge lineage evolutionarily distant from demosponges. Surprisingly, the phylogenetic analyses of identified DTFs revealed striking differences between the calcareous sponges and Amphimedon. As these differences appear to be a result of independent gene loss events in the two sponge lineages, the last common ancestor of sponges had to possess a much more diverse repertoire of DTFs than extant sponges. Developmental expression of sponge homologs of genes involved in specification of the Bilaterian endomesoderm and the neurosensory cells suggests that roles of many DTFs date back to the last common ancestor of all animals. Strikingly, even DTFs displaying apparent pan-metazoan conservation of sequence and function are not immune to being lost from individual species genomes. The quest for a comprehensive picture of the developmental toolkit in the last common metazoan ancestor is thus greatly benefitting from the increasing accessibility of sequencing, allowing comparisons of multiple genomes within each phylum.

  14. Sources of the Self: Scholarly Personae as Repertoires of Scholarly Selfhood.

    Directory of Open Access Journals (Sweden)

    H. Paul

    2016-12-01

    Full Text Available The concept of ‘scholarly personae’ emerged about a decade ago in the history of science. Since then it has increasingly been used both inside and outside the historical discipline. This article examines where this interest comes from, what shapes it takes, and what types of research it stimulates. The thesis advanced in this article is that interest in scholarly personae, defined as ideal-typical models of being a scholar, emerges from at least four different sources. (1 The theme enables historical theorists to develop a ‘philosophy of historical practices’. (2 It offers historians the possibility of writing an integrated history of the sciences and the humanities. (3 It challenges linear story lines in historical writing. (4 Last but not least, it stimulates moral reflection on contemporary models of being a scholar, if only by providing a vocabulary for those wishing to judge models like the ‘successful grant applicant’ on their relative merits. Bronnen van het zelf: wetenschappelijke personae als repertoires van wetenschappelijke identiteit. Een jaar of tien geleden deed het concept ‘wetenschappelijke personae’ zijn intrede in de wetenschapsgeschiedenis. Sindsdien wordt het zowel binnen als buiten de historische wetenschap in toenemende mate gebruikt. Dit artikel onderzoekt waar deze belangstelling vandaan komt, welke vormen zij aanneemt en wat voor typen onderzoek zij stimuleert. De these die het artikel ontvouwt, luidt dat interesse in wetenschappelijke personae, opgevat als ideaaltypische modellen van wetenschapper-zijn, uit tenminste vier verschillende bronnen voorkomt. (1 Het thema stelt geschiedtheoretici in staat een ‘filosofie van historische praktijken’ te ontwikkelen. (2 Het biedt historici de mogelijkheid een geïntegreerde geschiedenis van natuur- en geesteswetenschappen te schrijven. (3 Het stelt lineaire verhaallijnen in de geschiedschrijving ter discussie. (4 Last but not least stimuleert het concept

  15. Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates.

    Science.gov (United States)

    Brunet, Frédéric G; Volff, Jean-Nicolas; Schartl, Manfred

    2016-06-03

    The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.

  16. Sequencing and characterisation of an extensive Atlantic salmon (Salmo salar L. microRNA repertoire.

    Directory of Open Access Journals (Sweden)

    Michaël Bekaert

    Full Text Available Atlantic salmon (Salmo salar L., a member of the family Salmonidae, is a totemic species of ecological and cultural significance that is also economically important in terms of both sports fisheries and aquaculture. These factors have promoted the continuous development of genomic resources for this species, furthering both fundamental and applied research. MicroRNAs (miRNA are small endogenous non-coding RNA molecules that control spatial and temporal expression of targeted genes through post-transcriptional regulation. While miRNA have been characterised in detail for many other species, this is not yet the case for Atlantic salmon. To identify miRNAs from Atlantic salmon, we constructed whole fish miRNA libraries for 18 individual juveniles (fry, four months post hatch and characterised them by Illumina high-throughput sequencing (total of 354,505,167 paired-ended reads. We report an extensive and partly novel repertoire of miRNA sequences, comprising 888 miRNA genes (547 unique mature miRNA sequences, quantify their expression levels in basal conditions, examine their homology to miRNAs from other species and identify their predicted target genes. We also identify the location and putative copy number of the miRNA genes in the draft Atlantic salmon reference genome sequence. The Atlantic salmon miRNAs experimentally identified in this study provide a robust large-scale resource for functional genome research in salmonids. There is an opportunity to explore the evolution of salmonid miRNAs following the relatively recent whole genome duplication event in salmonid species and to investigate the role of miRNAs in the regulation of gene expression in particular their contribution to variation in economically and ecologically important traits.

  17. Genomic architecture of MHC-linked odorant receptor gene repertoires among 16 vertebrate species.

    Science.gov (United States)

    Santos, Pablo Sandro Carvalho; Kellermann, Thomas; Uchanska-Ziegler, Barbara; Ziegler, Andreas

    2010-09-01

    The recent sequencing and assembly of the genomes of different organisms have shown that almost all vertebrates studied in detail so far have one or more clusters of genes encoding odorant receptors (OR) in close physical linkage to the major histocompatibility complex (MHC). It has been postulated that MHC-linked OR genes could be involved in MHC-influenced mate choice, comprising both pre- as well as post-copulatory mechanisms. We have therefore carried out a systematic comparison of protein sequences of these receptors from the genomes of man, chimpanzee, gorilla, orangutan, rhesus macaque, mouse, rat, dog, cat, cow, pig, horse, elephant, opossum, frog and zebra fish (amounting to a total of 559 protein sequences) in order to identify OR families exhibiting evolutionarily conserved MHC linkage. In addition, we compared the genomic structure of this region within these 16 species, accounting for presence or absence of OR gene families, gene order, transcriptional orientation and linkage to the MHC or framework genes. The results are presented in the form of gene maps and phylogenetic analyses that reveal largely concordant repertoires of gene families, at least among tetrapods, although each of the eight taxa studied (primates, rodents, ungulates, carnivores, proboscids, marsupials, amphibians and teleosts) exhibits a typical architecture of MHC (or MHC framework loci)-linked OR genes. Furthermore, the comparison of the genomic organization of this region has implications for phylogenetic relationships between closely related taxa, especially in disputed cases such as the evolutionary history of even- and odd-toed ungulates and carnivores. Finally, the largely conserved linkage between distinct OR genes and the MHC supports the concept that particular alleles within a given haplotype function in a concerted fashion during self-/non-self-discrimination processes in reproduction.

  18. The opsin repertoire of Jenynsia onca: a new perspective on gene duplication and divergence in livebearers

    Directory of Open Access Journals (Sweden)

    Owens Gregory L

    2009-08-01

    Full Text Available Abstract Background Jenynsia onca, commonly known as the one sided livebearer, is a member of the family Anablepidae. The opsin gene repertoires of J. onca's close relatives, the four-eyed fish (Anableps anableps and the guppy (Poecilia reticulata, have been characterized and each found to include one unique LWS opsin. Currently, the relationship among LWS paralogs and orthologs in these species are unclear, making it difficult to test the hypotheses that link vision to morphology or life history traits. The phylogenetic signal appears to have been disrupted by gene conversion. Here we have sequenced the opsin genes of J. onca in order to resolve these relationships. Findings We identified nine visual opsins; LWS S180r, LWS S180, LWS P180, SWS1, SWS2A, SWS2B, RH1, RH2-1, and RH2-2. Key site analysis revealed only one unique haplotype, RH2-2, although this is unlikely to shift λmax significantly. LWS P180 was found to be a product of a gene conversion event with LWS S180, followed by convergence to a proline residue at the 180 site. Conclusion Jenynsia onca has at least 9 visual opsins: three LWS, one RH1, two RH2, one SWS1 and two SWS2. The presence of LWS P180 moves the location of the LWS P180-S180 tandem duplication event back to the base of the Poeciliidae-Anablepidae clade, expanding the number of species possessing this unusual blue shifted LWS opsin. The presence of the LWS P180 gene also confirms that gene conversion events have homogenized opsin paralogs in fish, just as they have in humans.

  19. Identification of Complete Repertoire of Apis florea Odorant Receptors Reveals Complex Orthologous Relationships with Apis mellifera.

    Science.gov (United States)

    Karpe, Snehal D; Jain, Rikesh; Brockmann, Axel; Sowdhamini, Ramanathan

    2016-09-26

    We developed a computational pipeline for homology based identification of the complete repertoire of olfactory receptor (OR) genes in the Asian honey bee species, Apis florea Apis florea is phylogenetically the most basal honey bee species and also the most distant sister species to the Western honey bee Apis mellifera, for which all OR genes had been identified before. Using our pipeline, we identified 180 OR genes in A. florea, which is very similar to the number of ORs identified in A. mellifera (177 ORs). Many characteristics of the ORs including gene structure, synteny of tandemly repeated ORs and basic phylogenetic clustering are highly conserved. The composite phylogenetic tree of A. florea and A. mellifera ORs could be divided into 21 clades which are in harmony with the existing Hymenopteran tree. However, we found a few nonorthologous OR relationships between both species as well as independent pseudogenization of ORs suggesting separate evolutionary changes. Particularly, a subgroup of the OR gene clade XI, which had been hypothesized to code cuticular hydrocarbon receptors showed a high number of species-specific ORs RNAseq analysis detected a total number of 145 OR transcripts in male and 162 in female antennae. Most of the OR genes were highly expressed on the female antennae. However, we detected five distinct male-biased OR genes, out of which three genes (AfOr11, AfOr18, AfOr170P) were shown to be male-biased in A. mellifera, too, thus corroborating a behavioral function in sex-pheromone communication.

  20. Killer immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease.

    Science.gov (United States)

    López-Hernández, Ruth; Campillo, Jose A; Legaz, Isabel; Valdés, Mariano; Salama, Hortensia; Boix, Francisco; Hernández-Martínez, A M; Eguia, Jorge; González-Martínez, G; Moya-Quiles, Maria R; Minguela, Alfredo; García-Alonso, Ana; Carballo, Fernando; Muro, Manuel

    2016-11-01

    Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.

  1. Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire.

    Science.gov (United States)

    Medvedovic, Jasna; Ebert, Anja; Tagoh, Hiromi; Tamir, Ido M; Schwickert, Tanja A; Novatchkova, Maria; Sun, Qiong; Huis In 't Veld, Pim J; Guo, Chunguang; Yoon, Hye Suk; Denizot, Yves; Holwerda, Sjoerd J B; de Laat, Wouter; Cogné, Michel; Shi, Yang; Alt, Frederick W; Busslinger, Meinrad

    2013-08-22

    The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the Eμ enhancer, IGCR1 insulator, or 3' regulatory region in the proximal Igh domain.

  2. GPU Generation of Large Varied Animated Crowds

    OpenAIRE

    Isaac Rudomin; Benjamín Hernández; Oriam de Gyves; Leonel Toledo; Ivan Rivalcoba; Sergio Ruiz

    2013-01-01

    ..We discuss several steps in the process of simulating and visualizing large and varied crowds in real time for consumer-level computers and graphic cards (GPUs). Animating varied crowds using a diversity of models and animations (assets) is complex and costly. One has to use models that are expensive if bought, take a long time to model, and consume too much memory and computing resources. We discuss methods for simulating, generating, animating and rendering crowds of varied aspect and a d...

  3. A new varied-time photonic crystals

    OpenAIRE

    Wu, Xiang-Yao; Ma, Ji; Liu, Xiao-Jing; Liang, Yu; Li, Hong; Chen, Wan-Jin; Yuan, Hong-chun; Li, Heng-Mei

    2015-01-01

    In this paper, we have firstly proposed a new one-dimensional varied-time photonic crystals, i.e., the refractive indices of media $A$ and $B$ are the time functions. We consider the varied-time photonic crystals of refractive indices period variation and calculate the transmissivity and electronic field distribution with and without defect layer, which are different from the conventional photonic crystals, which transmissivity and electronic field distribution are static, but the varied-time...

  4. Inflationary Phase with Time Varying Fundamental Constants

    CERN Document Server

    Berman, M S; Berman, Marcelo S.; Trevisan, Luis A.

    2002-01-01

    Following Barrow, and Barrow and collaborators, we find a cosmological JBD model, with varying speed of light and varying fine structure constant, where the deceleration parameter is -1,causing acceleration of the Universe.Indeed, we have an exponential inflationary phase. Plancks time, energy, length,etc.,might have had different numerical values in the past, than those available in the litterature, due to the varying values for speed of light, and gravitational constant.

  5. A new varied-time photonic crystals

    OpenAIRE

    2015-01-01

    In this paper, we have firstly proposed a new one-dimensional varied-time photonic crystals, i.e., the refractive indices of media $A$ and $B$ are the time functions. We consider the varied-time photonic crystals of refractive indices period variation and calculate the transmissivity and electronic field distribution with and without defect layer, which are different from the conventional photonic crystals, which transmissivity and electronic field distribution are static, but the varied-time...

  6. Nonstationary Feller process with time-varying coefficients

    Science.gov (United States)

    Masoliver, Jaume

    2016-01-01

    We study the nonstationary Feller process with time varying coefficients. We obtain the exact probability distribution exemplified by its characteristic function and cumulants. In some particular cases we exactly invert the distribution and achieve the probability density function. We show that for sufficiently long times this density approaches a Γ distribution with time-varying shape and scale parameters. Not far from the origin the process obeys a power law with an exponent dependent of time, thereby concluding that accessibility to the origin is not static but dynamic. We finally discuss some possible applications of the process.

  7. Time varying effects in survival analysis

    DEFF Research Database (Denmark)

    Scheike, Thomas H.

    2002-01-01

    additive risk model; counting process; proportional hazards model; semi-parametric models; survival data; time-varying effects; nonparametric testing......additive risk model; counting process; proportional hazards model; semi-parametric models; survival data; time-varying effects; nonparametric testing...

  8. Fractal analysis of time varying data

    Science.gov (United States)

    Vo-Dinh, Tuan; Sadana, Ajit

    2002-01-01

    Characteristics of time varying data, such as an electrical signal, are analyzed by converting the data from a temporal domain into a spatial domain pattern. Fractal analysis is performed on the spatial domain pattern, thereby producing a fractal dimension D.sub.F. The fractal dimension indicates the regularity of the time varying data.

  9. Robust linear parameter varying induction motor control with polytopic models

    Directory of Open Access Journals (Sweden)

    Dalila Khamari

    2013-01-01

    Full Text Available This paper deals with a robust controller for an induction motor which is represented as a linear parameter varying systems. To do so linear matrix inequality (LMI based approach and robust Lyapunov feedback controller are associated. This new approach is related to the fact that the synthesis of a linear parameter varying (LPV feedback controller for the inner loop take into account rotor resistance and mechanical speed as varying parameter. An LPV flux observer is also synthesized to estimate rotor flux providing reference to cited above regulator. The induction motor is described as a polytopic model because of speed and rotor resistance affine dependence their values can be estimated on line during systems operations. The simulation results are presented to confirm the effectiveness of the proposed approach where robustness stability and high performances have been achieved over the entire operating range of the induction motor.

  10. Mixing properties of ARCH and time-varying ARCH processes

    CERN Document Server

    Fryzlewicz, Piotr; 10.3150/10-BEJ270

    2011-01-01

    There exist very few results on mixing for non-stationary processes. However, mixing is often required in statistical inference for non-stationary processes such as time-varying ARCH (tvARCH) models. In this paper, bounds for the mixing rates of a stochastic process are derived in terms of the conditional densities of the process. These bounds are used to obtain the $\\alpha$, 2-mixing and $\\beta$-mixing rates of the non-stationary time-varying $\\operatorname {ARCH}(p)$ process and $\\operatorname {ARCH}(\\infty)$ process. It is shown that the mixing rate of the time-varying $\\operatorname {ARCH}(p)$ process is geometric, whereas the bound on the mixing rate of the $\\operatorname {ARCH}(\\infty)$ process depends on the rate of decay of the $\\operatorname {ARCH}(\\infty)$ parameters. We note that the methodology given in this paper is applicable to other processes.

  11. Sources of the Self: Scholarly Personae as Repertoires of Scholarly Selfhood

    Directory of Open Access Journals (Sweden)

    Herman Paul

    2016-12-01

    Full Text Available The concept of ‘scholarly personae’ emerged about a decade ago in the history of science. Since then it has increasingly been used both inside and outside the historical discipline. This article examines where this interest comes from, what shapes it takes, and what types of research it stimulates. The thesis advanced in this article is that interest in scholarly personae, defined as ideal-typical models of being a scholar, emerges from at least four different sources. (1 The theme enables historical theorists to develop a ‘philosophy of historical practices’. (2 It offers historians the possibility of writing an integrated history of the sciences and the humanities. (3 It challenges linear story lines in historical writing. (4 Last but not least, it stimulates moral reflection on contemporary models of being a scholar, if only by providing a vocabulary for those wishing to judge models like the ‘successful grant applicant’ on their relative merits. Bronnen van het zelf: wetenschappelijke personae als repertoires van wetenschappelijke identiteitEen jaar of tien geleden deed het concept ‘wetenschappelijke personae’ zijn intrede in de wetenschapsgeschiedenis. Sindsdien wordt het zowel binnen als buiten de historische wetenschap in toenemende mate gebruikt. Dit artikel onderzoekt waar deze belangstelling vandaan komt, welke vormen zij aanneemt en wat voor typen onderzoek zij stimuleert. De these die het artikel ontvouwt, luidt dat interesse in wetenschappelijke personae, opgevat als ideaaltypische modellen van wetenschapper-zijn, uit tenminste vier verschillende bronnen voorkomt. (1 Het thema stelt geschiedtheoretici in staat een ‘filosofie van historische praktijken’ te ontwikkelen. (2 Het biedt historici de mogelijkheid een geïntegreerde geschiedenis van natuur- en geesteswetenschappen te schrijven. (3 Het stelt lineaire verhaallijnen in de geschiedschrijving ter discussie. (4 Last but not least stimuleert het concept morele

  12. Evolution and origin of vomeronasal-type odorant receptor gene repertoire in fishes

    Directory of Open Access Journals (Sweden)

    Nishida Mutsumi

    2006-10-01

    Full Text Available Abstract Background In teleost fishes that lack a vomeronasal organ, both main odorant receptors (ORs and vomeronasal receptors family 2 (V2Rs are expressed in the olfactory epithelium, and used for perception of water-soluble chemicals. In zebrafish, it is known that both ORs and V2Rs formed multigene families of about a hundred copies. Whereas the contribution of V2Rs in zebrafish to olfaction has been found to be substantially large, the composition and structure of the V2R gene family in other fishes are poorly known, compared with the OR gene family. Results To understand the evolutionary dynamics of V2R genes in fishes, V2R sequences in zebrafish, medaka, fugu, and spotted green pufferfish were identified from their draft genome sequences. There were remarkable differences in the number of intact V2R genes in different species. Most V2R genes in these fishes were tightly clustered in one or two specific chromosomal regions. Phylogenetic analysis revealed that the fish V2R family could be subdivided into 16 subfamilies that had diverged before the separation of the four fishes. Genes in two subfamilies in zebrafish and another subfamily in medaka increased in their number independently, suggesting species-specific evolution in olfaction. Interestingly, the arrangements of V2R genes in the gene clusters were highly conserved among species in the subfamily level. A genomic region of tetrapods corresponding to the region in fishes that contains the V2R cluster was found to have no V2R gene in any species. Conclusion Our results have indicated that the evolutionary dynamics of fish V2Rs are characterized by rapid gene turnover and lineage-specific phylogenetic clustering. In addition, the present phylogenetic and comparative genome analyses have shown that the fish V2Rs have expanded after the divergence between teleost and tetrapod lineages. The present identification of the entire V2R repertoire in fishes would provide useful foundation to

  13. Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity.

    Directory of Open Access Journals (Sweden)

    Haiyan Huang

    Full Text Available UDP-glucuronosyltransferases (Ugts are a supergene family of phase II drug-metabolizing enzymes that catalyze the conjugation of numerous hydrophobic small molecules with the UDP-glucuronic acid, converting them into hydrophilic molecules. Here, we report the identification and cloning of the complete zebrafish Ugt gene repertoire. We found that the zebrafish genome contains 45 Ugt genes that can be divided into three families: Ugt1, Ugt2, and Ugt5. Both Ugt1 and Ugt2 have two unlinked clusters: a and b. The Ugt1a, Ugt1b, Ugt2a, and Ugt2b clusters each contain variable and constant regions, similar to that of the protocadherin (Pcdh, immunoglobulin (Ig, and T-cell receptor (Tcr clusters. Cloning the full-length coding sequences confirmed that each of the variable exons is separately spliced to the set of constant exons within each zebrafish Ugt cluster. Comparative analyses showed that both a and b clusters of the zebrafish Ugt1 and Ugt2 genes have orthologs in other teleosts, suggesting that they may be resulted from the "fish-specific" whole-genome duplication event. The Ugt5 genes are a novel family of Ugt genes that exist in teleosts and amphibians. Their entire open reading frames are encoded by single large exons. The zebrafish Ugt1, Ugt2, and Ugt5 genes can generate additional transcript diversity through alternative splicing. Based on phylogenetic analyses, we propose that the ancestral tetrapod and teleost Ugt1 clusters contained multiple Ugt1 paralogs. After speciation, these ancestral Ugt1 clusters underwent lineage-specific gene loss and duplication. The ancestral vertebrate Ugt2 cluster also underwent lineage-specific duplication. The intronless Ugt5 open reading frames may be derived from retrotransposition followed by gene duplication. They have been expanded dramatically in teleosts and have become the most abundant Ugt family in these lineages. These findings have interesting implications regarding the molecular evolution of

  14. Poverty Index With Time Varying Consumption and Income Distributions

    CERN Document Server

    Chattopadhyay, Amit K; Mallick, Sushanta K

    2016-01-01

    In a recent work (Chattopadhyay, A. K. et al, Europhys. Lett. {\\bf 91}, 58003, 2010) based on food consumption statistics, we showed how a stochastic agent based model could represent the time variation of the income distribution statistics in a developing economy, thereby defining an alternative \\enquote{poverty index} (PI) that largely agreed with poverty gap index data. This PI used two variables, the probability density function of the income statistics and a consumption deprivation (CD) function, representing the shortfall in the minimum consumption needed for survival. Since the time dependence of the CD function was introduced there through data extrapolation only and not through an endogenous time dependent series, this model left unexplained how the minimum consumption needed for survival varies with time. The present article overcomes these limitations and arrives at a new unified theoretical structure through time varying consumption and income distributions where trade is only allowed when the inc...

  15. The role of the pineal gland in the photoperiodic control of bird song frequency and repertoire in the house sparrow, Passer domesticus.

    Science.gov (United States)

    Wang, Gang; Harpole, Clifford E; Paulose, Jiffin; Cassone, Vincent M

    2014-04-01

    Temperate zone birds are highly seasonal in many aspects of their physiology. In mammals, but not in birds, the pineal gland is an important component regulating seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead affects seasonal changes in brain song control structures, suggesting the pineal gland regulates seasonal song behavior. The present study tests the hypothesis that the pineal gland transduces photoperiodic information to the control of seasonal song behavior to synchronize this important behavior to the appropriate phenology. House sparrows, Passer domesticus, expressed a rich array of vocalizations ranging from calls to multisyllabic songs and motifs of songs that varied under a regimen of different photoperiodic conditions that were simulated at different times of year. Control (SHAM) birds exhibited increases in song behavior when they were experimentally transferred from short days, simulating winter, to equinoctial and long days, simulating summer, and decreased vocalization when they were transferred back to short days. When maintained in long days for longer periods, the birds became reproductively photorefractory as measured by the yellowing of the birds' bills; however, song behavior persisted in the SHAM birds, suggesting a dissociation of reproduction from the song functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in daily vocal rate and song repertoire size than did the SHAM birds during the long summer days. These increases gradually declined upon the extension of the long days and did not respond to the transfer to short days as was observed in the SHAM birds, suggesting that the pineal gland conveys photoperiodic information to the vocal control system, which in turn regulates song behavior.

  16. Vocal repertoire of free-ranging black howler monkeys' (Alouatta pigra): Call types, contexts, and sex-related contributions.

    Science.gov (United States)

    Briseño-Jaramillo, Margarita; Biquand, Véronique; Estrada, Alejandro; Lemasson, Alban

    2017-01-17

    Alouatta species utter the most powerful primate vocalizations in the Neotropics and are well-known for their loud and long-lasting male howling bouts. However, the diversity of acoustic structures used in these howling bouts, as well as in non-howling contexts, and the relative contribution of the different group members to the entire vocal repertoire, needed to be explored further. This report provides the first detailed description of the vocal repertoire of black howler monkeys (Alouatta pigra), focusing on acoustic structures and contexts of emission of both loud and soft calls as well as on the contribution rate of males and females to the different call types. Three free-ranging social groups of black howler monkeys living in Palenque National Park, Mexico were monitored. We identified twelve acoustically discriminable call types, eight described previously and four described here for the first time. A few call types were systematically emitted either isolated or during howling bouts, but most of them could be heard in both calling contexts. Three call types were emitted only by females and two only by males. Adult males' call rates (for the seven shared call types) were higher than those of females but only when considering calls emitted within howling bouts. Our contextual analysis enabled us to divide call types into potential functional categories, according to their degree of contribution, to intra-group versus inter-group interactions and to neutral-positive versus negative situations. We then discussed how socio-ecological factors, notably sex differences in social behaviors, may explain the variability found in the vocal repertoire of this species and compared our findings with the literature on other primate species.

  17. Flexible Foraging of Ants under Unsteadily Varying Environment

    Science.gov (United States)

    Tao, Tomomi; Nakagawa, Hiroyuki; Yamasaki, Masato; Nishimori, Hiraku

    2004-08-01

    Using a simple model for the trail formation of ants, the relation between i) the schedule of feeding which represents the unsteady natural environment, ii) emerging patterns of trails connecting a nest with food resources, and iii) the foraging efficiency is studied. Simulations and a simple analysis show that the emergent trail pattern flexibly varies depending on the feeding schedule by which ants can make an efficient foraging according to the underlying unsteady environment.

  18. Varying Alpha and the Electroweak Model

    CERN Document Server

    Kimberly, D; Kimberly, Dagny; Magueijo, Joao

    2003-01-01

    Inspired by recent claims for a varying fine structure constant, alpha, we investigate the effect of ``promoting coupling constants to variables'' upon various parameters of the standard model. We first consider a toy model: Proca's theory of the massive photon. We then explore the electroweak theory with one and two dilaton fields. We find that a varying alpha unavoidably implies varying W and Z masses. This follows from gauge invariance, and is to be contrasted with Proca' theory. For the two dilaton theory the Weinberg angle is also variable, but Fermi's constant and the tree level fermion masses remain constant unless the Higgs' potential becomes dynamical. We outline some cosmological implications.

  19. Tavatult jahe Karlovy Vary / Jaanus Noormets

    Index Scriptorium Estoniae

    Noormets, Jaanus

    2011-01-01

    1.-10. juulini toimunud Karlovy Vary 46. filmifestivalist (muusikafilmide alajaotuses näidati Marianne Kõrveri dokumentaalfilmi "Erkki-Sven Tüür: 7 etüüdi piltides" (2010) programmis "A Musical Odyssey")

  20. Inhomogeneous Universe Models with Varying Cosmological Term

    CERN Document Server

    Chimento, L P; Chimento, Luis P.; Pavon, Diego

    1998-01-01

    The evolution of a class of inhomogeneous spherically symmetric universe models possessing a varying cosmological term and a material fluid, with an adiabatic index either constant or not, is studied.

  1. Effect of granulocyte colony-stimulating factor mobilization on the expression patterns, clonality and signal transduction of TRAV and TRBV repertoire.

    Science.gov (United States)

    Xuan, Li; Wu, Xiuli; Wu, Meiqing; Zhang, Yu; Liu, Hui; Fan, Zhiping; Sun, Jing; Liu, Qifa

    2012-08-01

    The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Recently, αβ(+) T cells are identified as the primary effector cells for GVHD. However, whether G-CSF could influence the repertoire of αβ(+) T cells (TRAV and TRBV repertoire) and CD3 genes remains unclear. To further characterize this feature, we investigated the effect of G-CSF mobilization on the T cell receptors (TCR) of αβ(+) T cells (TRAV and TRBV repertoire) and CD3 genes, as well as the association between the changes of TCR repertoire and GVHD in patients undergoing G-CSF mobilized allo-PBSCT. We found that G-CSF mobilization had an effect on the expression patterns, clonality and signal transduction of TRAV and TRBV repertoire. This alteration might play a role in mediating GVHD in G-CSF mobilized allo-PBSCT. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.

    Science.gov (United States)

    Sircar, Piya; Furr, Kathryn L; Dorosh, Lauren A; Letvin, Norman L

    2010-08-15

    Because it is thought that mucosal tissues play a fundamental role in early HIV/SIV infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. We have employed TCR repertoire analyses to define the clonal composition of a dominant SIV epitope-specific CD8(+) T cell population in mucosal and systemic compartments of SIV-infected rhesus monkeys during both acute and chronic infection. We show that the CD8(+) T cell repertoire in mucosal tissues of uninfected rhesus monkeys is oligoclonal, whereas the CD8(+) T cell repertoire in blood is polyclonal. Early postinfection, the SIV-specific CD8(+) T cell clonal repertoire is distinct in mucosal compartments and peripheral blood. However, we observed a narrowing of the virus-specific CD8(+) T cell clonal repertoire in all sampled anatomic compartments as infection progressed from acute to chronic, and there was comparable clonal diversity in all anatomic compartments. We showed during chronic infection that the same clonal populations of virus-specific CD8(+) T cells are present in all compartments. These data indicate that the SIV-specific CD8(+) T cells in systemic and mucosal sites have a shared clonal origin and are, therefore, capable of both responding to infection in the systemic circulation and trafficking to mucosal tissues.

  3. Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

    Science.gov (United States)

    Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

    2014-01-01

    High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

  4. CD8 T Cell Response Maturation Defined by Anentropic Specificity and Repertoire Depth Correlates with SIVΔnef-induced Protection

    Science.gov (United States)

    Adnan, Sama; Colantonio, Arnaud D.; Yu, Yi; Gillis, Jacqueline; Wong, Fay E.; Becker, Ericka A.; Reeves, R. Keith; Lifson, Jeffrey D.; O’Connor, Shelby L.; Johnson, R. Paul

    2015-01-01

    The live attenuated simian immunodeficiency virus (LASIV) vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective efficacy. Here, we exploit deep sequencing technology and comprehensive CD8 T cell epitope mapping to deconstruct the CD8 T cell response, to identify the regions of immune pressure and viral escape, and to delineate the effect of epitope escape on the evolution of the CD8 T cell response in SIVΔnef-vaccinated animals. We demonstrate that the initial CD8 T cell response in the acute phase of SIVΔnef infection is mounted predominantly against more variable epitopes, followed by widespread sequence evolution and viral escape. Furthermore, we show that epitope escape expands the CD8 T cell repertoire that targets highly conserved epitopes, defined as anentropic specificity, and generates de novo responses to the escaped epitope variants during the vaccination period. These results correlate SIVΔnef-induced protection with expanded anentropic specificity and increased response depth. Importantly, these findings render SIVΔnef, long the gold standard in HIV/SIV vaccine research, as a proof-of-concept vaccine that highlights the significance of the twin principles of anentropic specificity and repertoire depth in successful vaccine design. PMID:25688559

  5. Urban renewal, migration and memories: The affordances of place-based pedagogies for developing immigrant students’ literate repertoires

    Directory of Open Access Journals (Sweden)

    Barbara Comber

    2013-02-01

    Full Text Available This paper reports on the New literacy demands in the middle years of schooling project in which the affordances of placed-based pedagogy are being explored through teacher inquiries and classroom-based design experiments. The school is located within a large-scale urban renewal project in which houses are being demolished and families relocated. The original school buildings have recently been demolished and replaced by a large ‘Superschool’ which serves a bigger student population from a wider area. Drawing on both quantitative and qualitative data, the teachers reported that the language literacy learning of students (including a majority of students learning English as a second language involved in the project exceeded their expectations. The project provided the motivation for them to develop their oral language repertoires, by involving them in processes such as conducting interviews with adults for their oral histories, through questioning the project manager in regular meetings, and through reporting to their peers and the wider community at school assemblies. At the same time students’ written and multimodal documentation of changes in the neighbourhood and the school grounds extended their literate and semiotic repertoires as they produced books, reports, films, Powerpoints, visual designs and models of structures.

  6. Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell.

    Science.gov (United States)

    Kumar, Rashmi; Bach, Martina P; Mainoldi, Federica; Maruya, Mikako; Kishigami, Satoshi; Jumaa, Hassan; Wakayama, Teruhiko; Kanagawa, Osami; Fagarasan, Sidonia; Casola, Stefano

    2015-02-01

    In mammals, VDJ recombination is responsible for the establishment of a highly diversified preimmune antibody repertoire. Acquisition of a functional Ig heavy (H) chain variable (V) gene rearrangement is thought to prevent further recombination at the IgH locus. Here, we describe VHQ52(NT); Vκgr32(NT) Ig monoclonal mice reprogrammed from the nucleus of an intestinal IgA(+) plasma cell. In VHQ52(NT) mice, IgA replaced IgM to drive early B-cell development and peripheral B-cell maturation. In VHQ52(NT) animals, over 20% of mature B cells disrupted the single productive, nonautoimmune IgH rearrangement through VH replacement and exchanged it with a highly diversified pool of IgH specificities. VH replacement occurred in early pro-B cells, was independent of pre-B-cell receptor signaling, and involved predominantly one adjacent VH germ-line gene. VH replacement was also identified in 5% of peripheral B cells of mice inheriting a different productive VH rearrangement expressed in the form of an IgM H chain. In summary, editing of a productive IgH rearrangement through VH replacement can account for up to 20% of the IgH repertoire expressed by mature B cells.

  7. Reconstruction of ancestral chromosome architecture and gene repertoire reveals principles of genome evolution in a model yeast genus.

    Science.gov (United States)

    Vakirlis, Nikolaos; Sarilar, Véronique; Drillon, Guénola; Fleiss, Aubin; Agier, Nicolas; Meyniel, Jean-Philippe; Blanpain, Lou; Carbone, Alessandra; Devillers, Hugo; Dubois, Kenny; Gillet-Markowska, Alexandre; Graziani, Stéphane; Huu-Vang, Nguyen; Poirel, Marion; Reisser, Cyrielle; Schott, Jonathan; Schacherer, Joseph; Lafontaine, Ingrid; Llorente, Bertrand; Neuvéglise, Cécile; Fischer, Gilles

    2016-07-01

    Reconstructing genome history is complex but necessary to reveal quantitative principles governing genome evolution. Such reconstruction requires recapitulating into a single evolutionary framework the evolution of genome architecture and gene repertoire. Here, we reconstructed the genome history of the genus Lachancea that appeared to cover a continuous evolutionary range from closely related to more diverged yeast species. Our approach integrated the generation of a high-quality genome data set; the development of AnChro, a new algorithm for reconstructing ancestral genome architecture; and a comprehensive analysis of gene repertoire evolution. We found that the ancestral genome of the genus Lachancea contained eight chromosomes and about 5173 protein-coding genes. Moreover, we characterized 24 horizontal gene transfers and 159 putative gene creation events that punctuated species diversification. We retraced all chromosomal rearrangements, including gene losses, gene duplications, chromosomal inversions and translocations at single gene resolution. Gene duplications outnumbered losses and balanced rearrangements with 1503, 929, and 423 events, respectively. Gene content variations between extant species are mainly driven by differential gene losses, while gene duplications remained globally constant in all lineages. Remarkably, we discovered that balanced chromosomal rearrangements could be responsible for up to 14% of all gene losses by disrupting genes at their breakpoints. Finally, we found that nonsynonymous substitutions reached fixation at a coordinated pace with chromosomal inversions, translocations, and duplications, but not deletions. Overall, we provide a granular view of genome evolution within an entire eukaryotic genus, linking gene content, chromosome rearrangements, and protein divergence into a single evolutionary framework.

  8. CD8 T cell response maturation defined by anentropic specificity and repertoire depth correlates with SIVΔnef-induced protection.

    Directory of Open Access Journals (Sweden)

    Sama Adnan

    2015-02-01

    Full Text Available The live attenuated simian immunodeficiency virus (LASIV vaccine SIVΔnef is one of the most effective vaccines in inducing protection against wild-type lentiviral challenge, yet little is known about the mechanisms underlying its remarkable protective efficacy. Here, we exploit deep sequencing technology and comprehensive CD8 T cell epitope mapping to deconstruct the CD8 T cell response, to identify the regions of immune pressure and viral escape, and to delineate the effect of epitope escape on the evolution of the CD8 T cell response in SIVΔnef-vaccinated animals. We demonstrate that the initial CD8 T cell response in the acute phase of SIVΔnef infection is mounted predominantly against more variable epitopes, followed by widespread sequence evolution and viral escape. Furthermore, we show that epitope escape expands the CD8 T cell repertoire that targets highly conserved epitopes, defined as anentropic specificity, and generates de novo responses to the escaped epitope variants during the vaccination period. These results correlate SIVΔnef-induced protection with expanded anentropic specificity and increased response depth. Importantly, these findings render SIVΔnef, long the gold standard in HIV/SIV vaccine research, as a proof-of-concept vaccine that highlights the significance of the twin principles of anentropic specificity and repertoire depth in successful vaccine design.

  9. Analysis of the CDR3 Length Repertoire and the Diversity of TCRα Chain in Human Peripheral Blood T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Xinsheng Yao; Ying Diao; Wanbang Sun; Junmin Luo; Ming Qin; Xianying Tang

    2007-01-01

    Analysis of complementarity determining region 3 (CDR3) length of T lymphocyte receptors (TCRs) by immunoscope spectratyping technique has been used successfully to investigate the diversity of TCR in autoimmune diseases and infection diseases. In this study, we investigated the patterns of CDR3 length distribution for all 32 TCR AV gene families in human peripheral blood lymphocytes of four normal volunteers by the immunoscope spectratyping technique. It was found that PCR products exhibited an obscure band on 1.5% agarose gel electrophoresis. Each TCR AV family exhibited more than 8 bands on 6% sequencing gel electrophoresis. The CDR3 spectratyping of all TCR AV families showed a standard Gaussian distribution with different CDR3 length,and the expression frequency of CDR3 was similar among the gene families. Most of CDR3 in TCR AV family recombine in frame. However, some of the CDR3 showed out-of frame gene rearrangement. Additionally, we found that in some of TCR AV families there were 18 amino acid discrepancies between the longest CDR3 and shortest CDR3. These results may be helpful to further study the recombination mechanism of human TCR genes, the TCR CDR3 gene repertoire, and the repertoire drift in health people and disease state.

  10. Using molecular repertoires to identify high-affinity peptide ligands of the WW domain of human and mouse YAP.

    Science.gov (United States)

    Linn, H; Ermekova, K S; Rentschler, S; Sparks, A B; Kay, B K; Sudol, M

    1997-06-01

    The WW domain is a globular protein domain that is involved in mediating protein-protein interaction and that ultimately participates in various intracellular signaling events. The domain binds to polyproline ligands containing the xPPxY consensus (where x signifies any amino acid, P is proline and Y is tyrosine). One of the first WW domain-ligand links that was characterized in vitro was the WW domain of Yes-Associated Protein (YAP) and its WBP-1 ligand. To further characterize this molecular interaction, we used two independent approaches, both of which focused on the mutational analysis of the WBP-1 ligand. We screened repertoires of synthetic decamer peptides containing the xPPxY core of WBP-1 in which all ten positions were sequentially replaced with the remaining amino acids. In addition, we screened decamer repertoires with all permutations of the amino acids which individually increased the binding to the WW domain of YAP, as compared to the wild type. In a parallel approach, we used a phage-displayed combinatorial peptide library biased for the presence of two consecutive prolines to study ligand preferences for the WW domain of YAP. Interestingly, these two lines of investigation converged and yielded the core sequence PPPPYP, which is preferred by the YAP-WW domain. This sequence was found within the p53 (tumor suppressor) binding protein-2, a probable cognate or alternative ligand interacting with YAP.

  11. Quantitative measurement of pathogen specific human memory T cell repertoire diversity using a CDR3β-specific microarray

    Directory of Open Access Journals (Sweden)

    Gorski Jack

    2007-09-01

    Full Text Available Abstract Background Providing quantitative microarray data that is sensitive to very small differences in target sequence would be a useful tool in any number of venues where a sample can consist of a multiple related sequences present in various abundances. Examples of such applications would include measurement of pseudo species in viral infections and the measurement of species of antibodies or T cell receptors that constitute immune repertoires. Difficulties that must be overcome in such a method would be to account for cross-hybridization and for differences in hybridization efficiencies between the arrayed probes and their corresponding targets. We have used the memory T cell repertoire to an influenza-derived peptide as a test case for developing such a method. Results The arrayed probes were corresponded to a 17 nucleotide TCR-specific region that distinguished sequences differing by as little as a single nucleotide. Hybridization efficiency between highly related Cy5-labeled subject sequences was normalized by including an equimolar mixture of Cy3-labeled synthetic targets representing all 108 arrayed probes. The same synthetic targets were used to measure the degree of cross hybridization between probes. Reconstitution studies found the system sensitive to input ratios as low as 0.5% and accurate in measuring known input percentages (R2 = 0.81, R = 0.90, p 0.05. Conclusion This novel strategy appears to be robust and can be adapted to any situation where complex mixtures of highly similar sequences need to be quantitatively resolved.

  12. TIR-domain-containing protein repertoire of nine anthozoan species reveals coral-specific expansions and uncharacterized proteins.

    Science.gov (United States)

    Poole, Angela Z; Weis, Virginia M

    2014-10-01

    The intracellular toll/interleukin-1 receptor (TIR) domain plays an important role in vertebrate immunity, but the evolution and function of invertebrate TIR-domain-containing proteins is not fully understood. This study characterized and compared the TIR-domain-containing protein repertoire of nine cnidarians in class Anthozoa. A diverse set of proteins, including MyD88 (myeloid differentiation primary response protein 88), toll-like receptor (TLR)-like, interleukin-1 receptor (IL-1R)-like, and TIR-only proteins are present in the species surveyed. Increased numbers of TIR-only proteins were observed in corals compared to anemones, especially in the Acroporid and Pocilloporid coral families. This expansion could be linked to diversity of the microbial community on or in hosts and managing both positive and negative associations. Phylogenetic analysis indicates there are two groups of proteins with IL-1R-like domain architecture in anthozoans that potentially evolved independently of the vertebrate family. Bacterial-like TIR_2 domain proteins are also present, including one sequence with novel domain architecture. Overall this work promotes a better understanding of the anthozoan immune repertoire, which is important in the context learning about ancestral immune pathways and host-microbe interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Low structural variation in the host-defense peptide repertoire of the dwarf clawed frog Hymenochirus boettgeri (Pipidae.

    Directory of Open Access Journals (Sweden)

    Severine Matthijs

    Full Text Available THE skin secretion of many amphibians contains peptides that are able to kill a broad range of microorganisms (antimicrobial peptides: AMPs and potentially play a role in innate immune defense. Similar to the toxin arsenals of various animals, amphibian AMP repertoires typically show major structural variation, and previous studies have suggested that this may be the result of diversifying selection in adaptation to a diverse spectrum of pathogens. Here we report on transcriptome analyses that indicate a very different pattern in the dwarf clawed frog H. boettgeri. Our analyses reveal a diverse set of transcripts containing two to six tandem repeats, together encoding 14 distinct peptides. Five of these have recently been identified as AMPs, while three more are shown here to potently inhibit the growth of gram-negative bacteria, including multi-drug resistant strains of the medically important Pseudomonas aeruginosa. Although the number of predicted peptides is similar to the numbers of related AMPs in Xenopus and Silurana frog species, they show significantly lower structural variation. Selection analyses confirm that, in contrast to the AMPs of other amphibians, the H. boettgeri peptides did not evolve under diversifying selection. Instead, the low sequence variation among tandem repeats resulted from purifying selection, recent duplication and/or concerted gene evolution. Our study demonstrates that defense peptide repertoires of closely related taxa, after diverging from each other, may evolve under differential selective regimes, leading to contrasting patterns of structural diversity.

  14. Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ T Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Urban

    2010-01-01

    Full Text Available T cells develop into two major populations distinguished by their T cell receptor (TCR chains. Cells with the αβ TCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate γδ TCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vγ2Vδ2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature on γδ T cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen-reactive Vγ2Vδ2 cells. A unique mechanism for MHC-independent repertoire selection is linked to the control of effector function that is vital to the role for γδ T cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.

  15. EXPANDING URBAN AMERICAN INDIAN YOUTHS’ REPERTOIRE OF DRUG RESISTANCE SKILLS: PILOT RESULTS FROM A CULTURALLY ADAPTED PREVENTION PROGRAM

    Science.gov (United States)

    Kulis, Stephen; Dustman, Patricia A.; Brown, Eddie F.; Martinez, Marcos

    2013-01-01

    This article examines changes in the drug resistance strategies used by urban American Indian (UAI) middle school students during a pilot test of a substance use prevention curriculum designed specifically for UAI youth, Living in 2 Worlds (L2W). L2W teaches four drug resistance strategies (refuse, explain, avoid, leave [R-E-A-L]) in culturally appropriate ways. Data come from 57 UAI students (53% female; mean age = 12.5 years) who participated in L2W during an academic enrichment class for Native youth at two Phoenix schools. Students completed a pre-test questionnaire before the L2W lessons and a post-test 7 months later. Questions assessed the use of R-E-A-L and alternative strategies commonly reported by UAI youth (change the subject, use humor). Tests of mean differences from pre-test to post-test showed significant increases in use of refuse, R-E-A-L repertoire. Use of more passive strategies (avoid, use humor) did not change significantly, except for change the subject, which increased. Changes in the use of strategies did not differ significantly by gender, age, school grades, parental education, or length of urban residence. The L2W curriculum appears effective in teaching culturally relevant communication strategies that expand UAI youths’ repertoire of drug resistance skills. PMID:23529769

  16. Digital repetitive control under varying frequency conditions

    CERN Document Server

    Ramos, Germán A; Olm, Josep M

    2013-01-01

    The tracking/rejection of periodic signals constitutes a wide field of research in the control theory and applications area. Repetitive Control has proven to be an efficient way to face this topic. However, in some applications the frequency of the reference/disturbance signal is time-varying or uncertain. This causes an important performance degradation in the standard Repetitive Control scheme. This book presents some solutions to apply Repetitive Control in varying frequency conditions without loosing steady-state performance. It also includes a complete theoretical development and experimental results in two representative systems. The presented solutions are organized in two complementary branches: varying sampling period Repetitive Control and High Order Repetitive Control. The first approach allows dealing with large range frequency variations while the second allows dealing with small range frequency variations. The book also presents applications of the described techniques to a Roto-magnet plant and...

  17. Varying alpha and the electroweak model

    Energy Technology Data Exchange (ETDEWEB)

    Kimberly, Dagny; Magueijo, Joao

    2004-03-25

    Inspired by recent claims for a varying fine structure constant, alpha, we investigate the effect of 'promoting coupling constants to variables' upon various parameters of the standard model. We first consider a toy model: Proca theory of the massive photon. We then explore the electroweak theory with one and two dilaton fields. We find that a varying alpha unavoidably implies varying W and Z masses. This follows from gauge invariance, and is to be contrasted with Proca theory. For the two dilaton theory the Weinberg angle is also variable, but Fermi's constant and the tree level fermion masses remain constant unless the Higgs potential becomes dynamical. We outline some cosmological implications.

  18. Solar mass-varying neutrino oscillations.

    Science.gov (United States)

    Barger, V; Huber, Patrick; Marfatia, Danny

    2005-11-18

    We propose that the solar neutrino deficit may be due to oscillations of mass-varying neutrinos (MaVaNs). This scenario elucidates solar neutrino data beautifully while remaining comfortably compatible with atmospheric neutrino and K2K data and with reactor antineutrino data at short and long baselines (from CHOOZ and KamLAND). We find that the survival probability of solar MaVaNs is independent of how the suppression of neutrino mass caused by the acceleron-matter couplings varies with density. Measurements of MeV and lower energy solar neutrinos will provide a rigorous test of the idea.

  19. Identification of I-7 expands the repertoire of genes for resistance to Fusarium wilt in tomato to three resistance gene classes.

    Science.gov (United States)

    Gonzalez-Cendales, Yvonne; Catanzariti, Ann-Maree; Baker, Barbara; Mcgrath, Des J; Jones, David A

    2016-04-01

    The tomato I-3 and I-7 genes confer resistance to Fusarium oxysporum f. sp. lycopersici (Fol) race 3 and were introgressed into the cultivated tomato, Solanum lycopersicum, from the wild relative Solanum pennellii. I-3 has been identified previously on chromosome 7 and encodes an S-receptor-like kinase, but little is known about I-7. Molecular markers have been developed for the marker-assisted breeding of I-3, but none are available for I-7. We used an RNA-seq and single nucleotide polymorphism (SNP) analysis approach to map I-7 to a small introgression of S. pennellii DNA (c. 210 kb) on chromosome 8, and identified I-7 as a gene encoding a leucine-rich repeat receptor-like protein (LRR-RLP), thereby expanding the repertoire of resistance protein classes conferring resistance to Fol. Using an eds1 mutant of tomato, we showed that I-7, like many other LRR-RLPs conferring pathogen resistance in tomato, is EDS1 (Enhanced Disease Susceptibility 1) dependent. Using transgenic tomato plants carrying only the I-7 gene for Fol resistance, we found that I-7 also confers resistance to Fol races 1 and 2. Given that Fol race 1 carries Avr1, resistance to Fol race 1 indicates that I-7-mediated resistance, unlike I-2- or I-3-mediated resistance, is not suppressed by Avr1. This suggests that Avr1 is not a general suppressor of Fol resistance in tomato, leading us to hypothesize that Avr1 may be acting against an EDS1-independent pathway for resistance activation. The identification of I-7 has allowed us to develop molecular markers for marker-assisted breeding of both genes currently known to confer Fol race 3 resistance (I-3 and I-7). Given that I-7-mediated resistance is not suppressed by Avr1, I-7 may be a useful addition to I-3 in the tomato breeder's toolbox.

  20. Bossy and nice requests: varying language register in speakers with autism spectrum disorder (ASD).

    Science.gov (United States)

    Volden, Joanne; Sorenson, Autumn

    2009-01-01

    The ability to vary language style or register is important for successfully navigating social situations. For example, we speak differently to our boss than we do to our children. This project examined whether high-functioning speakers with ASD were able to vary the language used for requests along continua of "politeness/bossiness", whether any such adjustments were similar to those made by appropriately matched controls, and whether speakers with ASD were able to accurately interpret politeness/bossiness registers. High-functioning children and adolescents (aged 6-16) with ASD were compared to matched typically developing children and adolescents on ability to (1) produce both "nice" and "bossy" requests to puppet listeners and, (2) to judge which of two requests was more polite. Contrary to expectations, participants with ASD were as adept as controls in both producing and judging polite and bossy requests. These results suggest that, at least for high-functioning children and adolescents with ASD, some skill at adjusting language register exists in their repertoire. Future research should examine whether this skill is also present in younger children and in unstructured interactions. If these results hold, clinicians may be able to focus their intervention on teaching strategies for successful use of behaviours that already exist rather than training the responses themselves. The reader will become familiar with the functional importance of varying language registers or style according to situational demands. In addition, teaching a strategy for how to determine when a particular language behaviour should be used may sometimes be more effective than training the specific language response.

  1. Filmihullu eluvesi voolab Karlovy Varys / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2010-01-01

    Karlovy Vary rahvusvahelisest filmifestivalist. Filmidest "Mr. Nobody" (rež. Jaco Van Dormaeli), "Kasside ema Teresa" (rež. Pawel Sala) ja "The Arbor" (rež. Clio Barnardi). Nimekiri võitnud töödest ja viimastel aastatel festivalil näidatud Eesti mängufilmidest

  2. Efficient Estimation in Heteroscedastic Varying Coefficient Models

    Directory of Open Access Journals (Sweden)

    Chuanhua Wei

    2015-07-01

    Full Text Available This paper considers statistical inference for the heteroscedastic varying coefficient model. We propose an efficient estimator for coefficient functions that is more efficient than the conventional local-linear estimator. We establish asymptotic normality for the proposed estimator and conduct some simulation to illustrate the performance of the proposed method.

  3. Cosmo MSW effect for mass varying neutrinos

    CERN Document Server

    Hung, P Q; Hung, Pham Quang; P\\"as, Heinrich

    2003-01-01

    We consider neutrinos with varying masses which arise in scenarios relating neutrino masses to the dark energy density in the universe. We point out that the neutrino mass variation can lead to level crossing and thus a cosmo MSW effect, having dramatic consequences for the flavor ratio of astrophysical neutrinos and the composition of the relic neutrino background.

  4. Õunpuu Karlovy Varys edukas

    Index Scriptorium Estoniae

    2010-01-01

    45. Karlovy Vary filmifestivali võistlusprogrammis "East of the West" märgiti ära Veiko Õunpuu film "Püha Tõnu kiusamine". Peaauhind läks rumeenlase Cristi Puiu filmile "Aurora". Grand prix´sai Augustĺ Vila film "La mosquitera". Teisi preemiasaajaid

  5. Filmihullu eluvesi voolab Karlovy Varys / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2010-01-01

    Karlovy Vary rahvusvahelisest filmifestivalist. Filmidest "Mr. Nobody" (rež. Jaco Van Dormaeli), "Kasside ema Teresa" (rež. Pawel Sala) ja "The Arbor" (rež. Clio Barnardi). Nimekiri võitnud töödest ja viimastel aastatel festivalil näidatud Eesti mängufilmidest

  6. Ellipsometry with randomly varying polarization states

    NARCIS (Netherlands)

    Liu, F.; Lee, C. J.; Chen, J. Q.; E. Louis,; van der Slot, P. J. M.; Boller, K. J.; F. Bijkerk,

    2012-01-01

    We show that, under the right conditions, one can make highly accurate polarization-based measurements without knowing the absolute polarization state of the probing light field. It is shown that light, passed through a randomly varying birefringent material has a well-defined orbit on the Poincar s

  7. Nicotine Dependence

    Science.gov (United States)

    Nicotine dependence Overview By Mayo Clinic Staff Nicotine dependence ― also called tobacco dependence ― is an addiction to tobacco products caused by the drug nicotine. Nicotine dependence means you can't stop using the substance, ...

  8. Vehicle routing problem with time-varying speed

    Institute of Scientific and Technical Information of China (English)

    LIU Yun-zhong

    2010-01-01

    Vehicle routing problem with time-varying speed(VRPTS)is a generalization of vehicle routing problem in which the travel speed between two locations depends on the passing areas and the time of a day.This paper proposes a simple model for estimating time-varying travel speeds in VRPTS that relieves much bur den to the data-related problems.The study further presents three heuristics(saving technique,proximity priority searching technique,and insertion technique)for VRPTS,developed by extending and modifying the existing heuristics for conventional VRP.The results of computational experiments demonstrate that the proposed estimation model performs well and the saving technique is the best among the three heuristics.

  9. Fault detection in reciprocating compressor valves under varying load conditions

    Science.gov (United States)

    Pichler, Kurt; Lughofer, Edwin; Pichler, Markus; Buchegger, Thomas; Klement, Erich Peter; Huschenbett, Matthias

    2016-03-01

    This paper presents a novel approach for detecting cracked or broken reciprocating compressor valves under varying load conditions. The main idea is that the time frequency representation of vibration measurement data will show typical patterns depending on the fault state. The problem is to detect these patterns reliably. For the detection task, we make a detour via the two dimensional autocorrelation. The autocorrelation emphasizes the patterns and reduces noise effects. This makes it easier to define appropriate features. After feature extraction, classification is done using logistic regression and support vector machines. The method's performance is validated by analyzing real world measurement data. The results will show a very high detection accuracy while keeping the false alarm rates at a very low level for different compressor loads, thus achieving a load-independent method. The proposed approach is, to our best knowledge, the first automated method for reciprocating compressor valve fault detection that can handle varying load conditions.

  10. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark

    Directory of Open Access Journals (Sweden)

    Dooley Helen

    2004-05-01

    Full Text Available Abstract Background Adult cartilaginous fish express three immunoglobulin (Ig isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3 with non-templated nucleotide (N-region addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. Results IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1 and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge within a species. Conclusion As in ratfish

  11. A comparison of reptilian and avian olfactory receptor gene repertoires: Species-specific expansion of group γ genes in birds

    Directory of Open Access Journals (Sweden)

    Kempenaers Bart

    2009-09-01

    Full Text Available Abstract Background The detection of odorants is mediated by olfactory receptors (ORs. ORs are G-protein coupled receptors that form a remarkably large protein superfamily in vertebrate genomes. We used data that became available through recent sequencing efforts of reptilian and avian genomes to identify the complete OR gene repertoires in a lizard, the green anole (Anolis carolinensis, and in two birds, the chicken (Gallus gallus and the zebra finch (Taeniopygia guttata. Results We identified 156 green anole OR genes, including 42 pseudogenes. The OR gene repertoire of the two bird species was substantially larger with 479 and 553 OR gene homologs in the chicken and zebra finch, respectively (including 111 and 221 pseudogenes, respectively. We show that the green anole has a higher fraction of intact OR genes (~72% compared with the chicken (~66% and the zebra finch (~38%. We identified a larger number and a substantially higher proportion of intact OR gene homologs in the chicken genome than previously reported (214 versus 82 genes and 66% versus 15%, respectively. Phylogenetic analysis showed that lizard and bird OR gene repertoires consist of group α, θ and γ genes. Interestingly, the vast majority of the avian OR genes are confined to a large expansion of a single branch (the so called γ-c clade. An analysis of the selective pressure on the paralogous genes of each γ-c clade revealed that they have been subjected to adaptive evolution. This expansion appears to be bird-specific and not sauropsid-specific, as it is lacking from the lizard genome. The γ-c expansions of the two birds do not intermix, i.e., they are lineage-specific. Almost all (group γ-c OR genes mapped to the unknown chromosome. The remaining OR genes mapped to six homologous chromosomes plus three to four additional chromosomes in the zebra finch and chicken. Conclusion We identified a surprisingly large number of potentially functional avian OR genes. Our data

  12. Varying-coefficient functional linear regression

    CERN Document Server

    Wu, Yichao; Müller, Hans-Georg; 10.3150/09-BEJ231

    2011-01-01

    Functional linear regression analysis aims to model regression relations which include a functional predictor. The analog of the regression parameter vector or matrix in conventional multivariate or multiple-response linear regression models is a regression parameter function in one or two arguments. If, in addition, one has scalar predictors, as is often the case in applications to longitudinal studies, the question arises how to incorporate these into a functional regression model. We study a varying-coefficient approach where the scalar covariates are modeled as additional arguments of the regression parameter function. This extension of the functional linear regression model is analogous to the extension of conventional linear regression models to varying-coefficient models and shares its advantages, such as increased flexibility; however, the details of this extension are more challenging in the functional case. Our methodology combines smoothing methods with regularization by truncation at a finite numb...

  13. Varying flexibilities in systems of organised decentralisation

    DEFF Research Database (Denmark)

    Ilsøe, Anna; Andersen, Søren Kaj

    information, collective agreements and interviews with representatives from tradeunions and employers' associations in Germany and Denmark. Based on our preliminary findings three explanatory theses for further research are developed in the article: 1) The level of specification, i.e. the level where...... response to this pressure from the company level can be described as a form of organised decentralisation in both countries, the response within the Danish collective bargaining system can be characterised as a proactive organised decentralisation while the response of the German system should rather...... be while the response of the German system should rather be interpreted as a reactive organised decentralisation. 3) The varying regulation of working time flexibility in Germany and Denmark implies varying risks in the regulation. In Germany lacking competencies in small or medium-sized companies lead...

  14. Varying flexibilities in systems of organised decentralisation

    DEFF Research Database (Denmark)

    Ilsøe, Anna; Andersen, Søren Kaj

    information, collective agreements and interviews with representatives from tradeunions and employers' associations in Germany and Denmark. Based on our preliminary findings three explanatory theses for further research are developed in the article: 1) The level of specification, i.e. the level where...... response to this pressure from the company level can be described as a form of organised decentralisation in both countries, the response within the Danish collective bargaining system can be characterised as a proactive organised decentralisation while the response of the German system should rather...... be while the response of the German system should rather be interpreted as a reactive organised decentralisation. 3) The varying regulation of working time flexibility in Germany and Denmark implies varying risks in the regulation. In Germany lacking competencies in small or medium-sized companies lead...

  15. Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire.

    Science.gov (United States)

    Liu, Ju; Li, Ruihua; Liu, Kun; Li, Liangliang; Zai, Xiaodong; Chi, Xiangyang; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-04-22

    High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies.

  16. Signaling Cascades: Consequences of Varying Substrate and Phosphatase Levels

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Knudsen, Michael; Wiuf, Carsten Henrik

    2012-01-01

    We study signaling cascades with an arbitrary number of layers of one-site phosphorylation cycles. Such cascades are abundant in nature and integrated parts of many pathways. Based on the Michaelis-Menten model of enzyme kinetics and the law of mass-action, we derive explicit analytic expressions...... for how the steady state concentrations and the total amounts of substrates, kinase, and phosphatates depend on each other. In particular, we use these to study how the responses (the activated substrates) vary as a function of the available amounts of substrates, kinase, and phosphatases. Our results...

  17. Identification and robust control of linear parameter-varying systems

    Science.gov (United States)

    Lee, Lawton Hubert

    This dissertation deals with linear parameter-varying (LPV) systems: linear dynamic systems that depend on time-varying parameters. These systems appear in gain scheduling problems, and much recent research has been devoted to their prospective usefulness for systematic gain scheduling. We primarily focus on robust control of uncertain LPV systems and identification of LPV systems that are modelable as linear-fractional transformations (LFTs). Using parameter-dependent quadratic Lyapunov functions, linear matrix inequalities (LMIs), and scaled small-gain arguments, we define notions of stability and induced-{cal L}sb2 performance for uncertain LPV systems whose parameters and rates of parameter variation satisfy given bounds. The performance criterion involves integral quadratic constraints and implies naturally parameter-dependent induced-{cal L}sb2 norm bounds. We formulate and solve an {cal H}sb{infty}-like control problem for an LPV plant with measurable parameters and an "Output/State Feedback" structure: the feedback outputs include some noiselessly measured states. Necessary and sufficient solvability conditions reduce to LMIs that can be solved approximately using finite-dimensional convex programming. Reduced-order LPV controllers are constructed from the LMI solutions. A D-K iteration-like procedure provides robustness to structured, time-varying, parametric uncertainty. The design method is applied to a motivating example: flight control for the F-16 VISTA throughout its subsonic flight envelope. Parameter-dependent weights and {cal H}sb{infty} design principles describe the performance objectives. Closed-loop responses exhibited by nonlinear simulations indicate satisfactory flying qualities. Identification of linear-fractional LPV systems is treated using maximum-likelihood parameter estimation. Computing the gradient and Hessian of a maximum-likelihood cost function reduces to simulating one LPV filter per identified parameter. We use nonlinear

  18. On a time varying fine structure constant

    CERN Document Server

    Berman, M S; Berman, Marcelo S.; Trevisan, Luis A.

    2001-01-01

    By employing Dirac LNH, and a further generalization by Berman (GLNH), we estimate how should vary the total number of nucleons, the energy density, Newton Gravitational constant, the cosmological constant, the magnetic permeability and electric permitivity, of the Universe,in order to account for the experimentally observed time variation of the fine structure constant. As a bonus,we find an acceptable value for the deceleration parameter of the present Universe, compatible with the Supernovae observations.

  19. Stabilization of Slowly Varying Switched Linear Systems

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bing; LIANG Tong

    2012-01-01

    The stabilization problem of systems that switch among a finite set of slowly varying linear systems with arbitrary switching frequency is discussed.It is shown that if the entries of the pointwise stabilizing feedback gain matrix are continuously differentiable functions of the entries of the system coefficient matrices,then the closed-loop system is uniformly asymptotically stable if the rate of time variation of the system coefficient matrices is sufficiently small.

  20. A Simultaneous Confidence Corridor for Varying Coefficient Regression with Sparse Functional Data

    OpenAIRE

    Gu, Lijie; Li WANG; Härdle, Wolfgang Karl; Yang, Lijian

    2014-01-01

    We consider a varying coefficient regression model for sparse functional data, with time varying response variable depending linearly on some time independent covariates with coefficients as functions of time dependent covariates. Based on spline smoothing, we propose data driven simultaneous confidence corridors for the coefficient functions with asymptotically correct confidence level. Such confidence corridors are useful benchmarks for statistical inference on the global shapes of coeffici...

  1. Reducing Raman noise in parametric frequency conversion by varying the input pump power

    DEFF Research Database (Denmark)

    Friis, Søren Michael Mørk; Andersen, Lasse Mejling; Rottwitt, Karsten

    2014-01-01

    The phase-matching condition of parametric frequency conversion and the impact of Raman scattering depend on the power of two separate pumps. We show that Raman noise is reduced by asymmetrically varying the pump powers.......The phase-matching condition of parametric frequency conversion and the impact of Raman scattering depend on the power of two separate pumps. We show that Raman noise is reduced by asymmetrically varying the pump powers....

  2. The globin gene repertoire of lampreys: convergent evolution of hemoglobin and myoglobin in jawed and jawless vertebrates.

    Science.gov (United States)

    Schwarze, Kim; Campbell, Kevin L; Hankeln, Thomas; Storz, Jay F; Hoffmann, Federico G; Burmester, Thorsten

    2014-10-01

    Agnathans (jawless vertebrates) occupy a key phylogenetic position for illuminating the evolution of vertebrate anatomy and physiology. Evaluation of the agnathan globin gene repertoire can thus aid efforts to reconstruct the origin and evolution of the globin genes of vertebrates, a superfamily that includes the well-known model proteins hemoglobin and myoglobin. Here, we report a comprehensive analysis of the genome of the sea lamprey (Petromyzon marinus) which revealed 23 intact globin genes and two hemoglobin pseudogenes. Analyses of the genome of the Arctic lamprey (Lethenteron camtschaticum) identified 18 full length and five partial globin gene sequences. The majority of the globin genes in both lamprey species correspond to the known agnathan hemoglobins. Both genomes harbor two copies of globin X, an ancient globin gene that has a broad phylogenetic distribution in the animal kingdom. Surprisingly, we found no evidence for an ortholog of neuroglobin in the lamprey genomes. Expression and phylogenetic analyses identified an ortholog of cytoglobin in the lampreys; in fact, our results indicate that cytoglobin is the only orthologous vertebrate-specific globin that has been retained in both gnathostomes and agnathans. Notably, we also found two globins that are highly expressed in the heart of P. marinus, thus representing functional myoglobins. Both genes have orthologs in L. camtschaticum. Phylogenetic analyses indicate that these heart-expressed globins are not orthologous to the myoglobins of jawed vertebrates (Gnathostomata), but originated independently within the agnathans. The agnathan myoglobin and hemoglobin proteins form a monophyletic group to the exclusion of functionally analogous myoglobins and hemoglobins of gnathostomes, indicating that specialized respiratory proteins for O2 transport in the blood and O2 storage in the striated muscles evolved independently in both lineages. This dual convergence of O2-transport and O2-storage proteins in

  3. Pervasive microRNA Duplication in Chelicerates: Insights from the Embryonic microRNA Repertoire of the Spider Parasteatoda tepidariorum.

    Science.gov (United States)

    Leite, Daniel J; Ninova, Maria; Hilbrant, Maarten; Arif, Saad; Griffiths-Jones, Sam; Ronshaugen, Matthew; McGregor, Alistair P

    2016-08-03

    MicroRNAs are small (∼22 nt) noncoding RNAs that repress translation and therefore regulate the production of proteins from specific target mRNAs. microRNAs have been found to function in diverse aspects of gene regulation within animal development and many other processes. Among invertebrates, both conserved and novel, lineage specific, microRNAs have been extensively studied predominantly in holometabolous insects such as Drosophila melanogaster However little is known about microRNA repertoires in other arthropod lineages such as the chelicerates. To understand the evolution of microRNAs in this poorly sampled subphylum, we characterized the microRNA repertoire expressed during embryogenesis of the common house spider Parasteatoda tepidariorum We identified a total of 148 microRNAs in P. tepidariorum representing 66 families. Approximately half of these microRNA families are conserved in other metazoans, while the remainder are specific to this spider. Of the 35 conserved microRNAs families 15 had at least two copies in the P. tepidariorum genome. A BLAST-based approach revealed a similar pattern of duplication in other spiders and a scorpion, but not among other chelicerates and arthropods, with the exception of a horseshoe crab. Among the duplicated microRNAs we found examples of lineage-specific tandem duplications, and the duplication of entire microRNA clusters in three spiders, a scorpion, and in a horseshoe crab. Furthermore, we found that paralogs of many P. tepidariorum microRNA families exhibit arm switching, which suggests that duplication was often followed by sub- or neofunctionalization. Our work shows that understanding the evolution of microRNAs in the chelicerates has great potential to provide insights into the process of microRNA duplication and divergence and the evolution of animal development.

  4. The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch.

    Science.gov (United States)

    Celik, Alexander A; Kraemer, Thomas; Huyton, Trevor; Blasczyk, Rainer; Bade-Döding, Christina

    2016-01-01

    Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell-mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes.

  5. Deep sequencing of the murine Igh repertoire reveals complex regulation of non-random V gene rearrangement frequencies

    Science.gov (United States)

    Choi, Nancy M.; Loguercio, Salvatore; Verma-Gaur, Jiyoti; Degner, Stephanie C.; Torkamani, Ali; Su, Andrew I.; Oltz, Eugene M.; Artyomov, Maxim; Feeney, Ann J.

    2013-01-01

    A diverse antibody repertoire is formed through the rearrangement of V, D, and J segments at the immunoglobulin heavy chain (Igh) loci. The C57BL/6 murine Igh locus has over 100 functional VH gene segments that can recombine to a rearranged DJH. While the non-random usage of VH genes is well documented, it is not clear what elements determine recombination frequency. To answer this question we conducted deep sequencing of 5′-RACE products of the Igh repertoire in pro-B cells, amplified in an unbiased manner. ChIP-seq results for several histone modifications and RNA polymerase II binding, RNA-seq for sense and antisense non-coding germline transcripts, and proximity to CTCF and Rad21 sites were compared to the usage of individual V genes. Computational analyses assessed the relative importance of these various accessibility elements. These elements divide the Igh locus into four epigenetically and transcriptionally distinct domains, and our computational analyses reveal different regulatory mechanisms for each region. Proximal V genes are relatively devoid of active histone marks and non-coding RNA in general, but having a CTCF site near their RSS is critical, suggesting that being positioned near the base of the chromatin loops is important for rearrangement. In contrast, distal V genes have higher levels of histone marks and non-coding RNA, which may compensate for their poorer RSSs and for being distant from CTCF sites. Thus, the Igh locus has evolved a complex system for the regulation of V(D)J rearrangement that is different for each of the four domains that comprise this locus. PMID:23898036

  6. Temporal Expression of Bim Limits the Development of Agonist-Selected Thymocytes and Skews Their TCRβ Repertoire

    Science.gov (United States)

    Li, Kun-Po; Fahnrich, Anke; Roy, Eron; Cuda, Carla M.; Grimes, H. Leighton; Perlman, Harris R.; Kalies, Kathrin; Hildeman, David A.

    2017-01-01

    CD8αα TCRαβ+ intestinal intraepithelial lymphocytes play a critical role in promoting intestinal homeostasis, although mechanisms controlling their development and peripheral homeostasis remain unclear. In this study, we examined the spatiotemporal role of Bim in the thymic selection of CD8αα precursors and the fate of these cells in the periphery. We found that T cell–specific expression of Bim during early/cortical, but not late/medullary, thymic development controls the agonist selection of CD8αα precursors and limits their private TCRβ repertoire. During this process, agonist-selected double-positive cells lose CD4/8 coreceptor expression and masquerade as double-negative (DN) TCRαβhi thymocytes. Although these DN thymocytes fail to re-express coreceptors after OP9-DL1 culture, they eventually mature and accumulate in the spleen where TCR and IL-15/STAT5 signaling promotes their conversion to CD8αα cells and their expression of gut-homing receptors. Adoptive transfer of splenic DN cells gives rise to CD8αα cells in the gut, establishing their precursor relationship in vivo. Interestingly, Bim does not restrict the IL-15–driven maturation of CD8αα cells that is critical for intestinal homeostasis. Thus, we found a temporal and tissue-specific role for Bim in limiting thymic agonist selection of CD8αα precursors and their TCRβ repertoire, but not in the maintenance of CD8αα intraepithelial lymphocytes in the intestine. PMID:27852740

  7. Hybridization leads to sensory repertoire expansion in a gynogenetic fish, the Amazon molly (poecilia formosa): a test of the hybrid-sensory expansion hypothesis.

    Science.gov (United States)

    Sandkam, Benjamin A; Joy, Jeffrey B; Watson, Corey T; Gonzalez-Bendiksen, Pablo; Gabor, Caitlin R; Breden, Felix

    2013-01-01

    Expansions in sensory systems usually require processes such as gene duplication and divergence, and thus evolve slowly. We evaluate a novel mechanism leading to rapid sensory repertoire expansion: hybrid-sensory expansion (HSE). HSE occurs when two species with differently tuned sensory systems form a hybrid, bringing together alleles from each of the parental species. In one generation, a sensory repertoire is created that is the sum of the variance between parental species. The Amazon molly presents a unique opportunity to test the HSE hypothesis in a "frozen" hybrid. We compared opsin sequences of the Amazon molly, Poecilia formosa, to those of the parental species. Both parental species are homozygous at the RH2-1 locus and each of the four long wavelength sensitive loci, while P. formosa possess two different alleles at these loci; one matching each parental allele. Gene expression analysis showed P. formosa use the expanded opsin repertoire that was the result of HSE. Additionally, behavioral tests revealed P. formosa respond to colored stimuli in a manner similar or intermediate to the parental species P. mexicana and P. latipinna. Together these results strongly support the HSE hypothesis. Hybrid-sensory repertoire expansion is likely important in other hybrid species and in other sensory systems.

  8. "Nobody Told Me They Didn't Speak English!": Teacher Language Views and Student Linguistic Repertoires in Hutterite Colony Schools in Canada

    Science.gov (United States)

    Sterzuk, Andrea; Nelson, Cynthia A.

    2016-01-01

    This article presents a qualitative study of five monolingual teachers' understandings of the linguistic repertoires of their multilingual students. These teachers deliver the Saskatchewan provincial curricula in English to Hutterite colony students who are users of three languages: (a) spoken Hutterisch as a home and community language, (b)…

  9. Anti-GITR Antibody Treatment Increases TCR Repertoire Diversity of Regulatory but not Effector T Cells Engaged in the Immune Response Against B16 Melanoma.

    Science.gov (United States)

    Scirka, Bozena; Szurek, Edyta; Pietrzak, Maciej; Rempala, Grzegorz; Kisielow, Pawel; Ignatowicz, Leszek; Miazek, Arkadiusz

    2017-06-21

    Crosslinking of glucocorticoid-induced TNF family-related receptor (GITR) with agonist antibodies restores cancer immunity by enhancing effector T cell (Teff) responses while interfering with intra-tumor regulatory T cell (Treg) stability and/or accumulation. However, how anti-GITR antibody infusion changes T cell receptor (TCR) repertoire of Teffs and Tregs engaged in anti-tumor immune response is unclear. Here, we used a transgenic mouse model (TCRmini) where T cells express naturally generated but limited TCR repertoire to trace the fate of individual T cells recognizing B16 melanoma in tumor-bearing mice, treated or non-treated with an anti-GITR monoclonal antibody DTA-1. Analysis of TCRs of CD4(+) T cells from these mice revealed that the TCR repertoire of dominant tumor-reactive Teff clones remained rather similar in treated and non-treated mice. In contrast, both tumor-associated and peripheral TCR repertoire of Tregs, which were mostly distinct from that of Teffs, underwent DTA-1 mediated remodeling characterized by depletion of dominant clones and an emergence of more diverse, low-frequency clones bearing increased numbers of TCRs shared with Teffs. We conclude that the DTA-1 infusion eliminates activated Tregs engaged in the initial maintenance of tolerogenic niche for tumor growth, but over time, it favors tumor replenishment by Tregs expressing an array of TCRs able to compete with Teffs for recognition of the same tumor antigens which may prevent its complete eradication.

  10. The influence of prior knowledge and viewing repertoire on learning from video

    NARCIS (Netherlands)

    de Boer, Jelle; Kommers, Petrus A.M.; de Brock, Bert; Tolboom, Jos

    2014-01-01

    Video is increasingly used as an instructional tool. It is therefore becoming more important to improve learning of students from video. We investigated whether student learning effects are influenced through an instruction about other viewing behaviours, and whether these learning effects depend on

  11. The influence of prior knowledge and viewing repertoire on learning from video

    NARCIS (Netherlands)

    Boer, de Jelle; Kommers, Piet A.M.; Brock, de Bert; Tolboom, Jos

    2014-01-01

    Video is increasingly used as an instructional tool. It is therefore becoming more important to improve learning of students from video. We investigated whether student learning effects are influenced through an instruction about other viewing behaviours, and whether these learning effects depend on

  12. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  13. Monitoring Pharmacologically Induced Immunosuppression by Immune Repertoire Sequencing to Detect Acute Allograft Rejection in Heart Transplant Patients: A Proof-of-Concept Diagnostic Accuracy Study

    Science.gov (United States)

    Valantine, Hannah A.; Penland, Lolita; Luikart, Helen; Strehl, Calvin; Cohen, Garrett; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    Background It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation. Methods and Findings In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412) that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without). We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient’s net state of immunosuppression (correlation with tacrolimus level, r = −0.867, 95% CI −0.968 to −0.523, p = 0.0014), as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9%) and a specificity of 82.0% (95% CI 72.1% to 89.1%) (cell-free donor-derived DNA as noninvasive gold standard). To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several

  14. Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission

    Science.gov (United States)

    Knight, Daniel R.; Squire, Michele M.; Collins, Deirdre A.; Riley, Thomas V.

    2017-01-01

    Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≤2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large “open” pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3

  15. Contagion dynamics in time-varying metapopulation networks

    Science.gov (United States)

    Perra, Nicola; Liu, Suyu; Baronchelli, Andrea

    2014-03-01

    The metapopulation framework is adopted in a wide array of disciplines to describe systems of well separated yet connected subpopulations. The subgroups/patches are often represented as nodes in a network whose links represent the migration routes among them. The connections has been so far mostly considered as static, but in general evolve in time. Here we address this case by investigating simple contagion processes on time-varying metapopulation networks. We focus on the SIR process, and determine analytically the mobility threshold for the onset of an epidemic spreading in the framework of activity-driven network models. We find profound differences from the case of static networks. The threshold is entirely described by the dynamical parameters defining the average number of instantaneously migrating individuals, and does not depend on the properties of the static network representation. Remarkably, the diffusion and contagion processes are slower in time-varying graphs than in their aggregated static counterparts, the mobility threshold been even two orders of magnitude larger in the first case. The presented results confirm the importance of considering the time-varying nature of complex networks.

  16. IMPre: an accurate and efficient software for prediction of T- and B-cell receptor germline genes and alleles from rearranged repertoire data

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-11-01

    Full Text Available Large-scale study of the properties of T-cell receptor (TCR and B-cell receptor (BCR repertoires through next-generation sequencing is providing excellent insights into the understanding of adaptive immune responses. Variable(DiversityJoining V(DJ germline genes and alleles must be characterized in detail to facilitate repertoire analyses. However, most species do not have well-characterized TCR/BCR germline genes because of their high homology. Also, more germline alleles are required for humans and other species, which limits the capacity for studying immune repertoires. Herein, we developed Immune Germline Prediction (IMPre, a tool for predicting germline V/J genes and alleles using deep-sequencing data derived from TCR/BCR repertoires. We developed a new algorithm, Seed_Clust, for clustering, produced a multiway tree for assembly and optimized the sequence according to the characteristics of rearrangement. We trained IMPre on human samples of T-cell receptor beta (TRB and immunoglobulin heavy chain (IGH, and then tested it on additional human samples. Accuracy of 97.7%, 100%, 92.9% and 100% was obtained for TRBV, TRBJ, IGHV and IGHJ, respectively. Analyses of subsampling performance for these samples showed IMPre to be robust using different data quantities. Subsequently, IMPre was tested on samples from rhesus monkeys and human long sequences: the highly accurate results demonstrated IMPre to be stable with animal and multiple data types. With rapid accumulation of high-throughput sequence data for TCR and BCR repertoires, IMPre can be applied broadly for obtaining novel genes and a large number of novel alleles. IMPre is available at https://github.com/zhangwei2015/IMPre.

  17. SLAP deficiency increases TCR avidity leading to altered repertoire and negative selection of cognate antigen-specific CD8+ T cells.

    Science.gov (United States)

    Friend, Samantha F; Peterson, Lisa K; Kedl, Ross M; Dragone, Leonard L

    2013-03-01

    How T cell receptor (TCR) avidity influences CD8(+) T cell development and repertoire selection is not yet fully understood. To fill this gap, we utilized Src-like adaptor protein (SLAP)-deficient mice as a tool to increase TCR avidity on double positive (DP) thymocytes. We generated SLAP(-/-) mice with the transgenic MHC class I-restricted TCR (OT-1) and SLAP(-/-) Vβ5 mice, expressing only the β-chain of the TCR OT-1 transgene, to examine the effects of increased TCR surface levels on CD8(+) T cell development and repertoire selection. In comparing SLAP(-/-) OT-1 and Vβ5 mice with wild-type controls, we performed compositional analysis and assessed thymocyte signaling by measuring CD5 levels. In addition, we performed tetramer and compositional staining to measure affinity for the cognate antigen, ovalbumin (OVA) peptide, presented by MHC. Furthermore, we quantified differences in α-chain repertoire in SLAP(-/-) Vβ5 mice. We have found that SLAP(-/-) OT-1 mice have fewer CD8(+) thymocytes but have increased CD5 expression. SLAP(-/-) OT-1 mice have fewer DP thymocytes expressing Vα2, signifying increased endogenous α-chain rearrangement, and more non-OVA-specific CD8(+) splenocytes upon tetramer staining. Our data demonstrate that SLAP(-/-) Vβ5 mice also have fewer OVA-specific cells and increased Vα2 usage in the peripheral Vβ5 CD8(+) T cells that were non-OVA-specific, demonstrating differences in α-chain repertoire. These studies provide direct evidence that increased TCR avidity in DP thymocytes enhances CD8(+) T cell negative selection deleting thymocytes with specificity for cognate antigen, an antigen the mature T cells may never encounter. Collectively, these studies provide new insights into how TCR avidity during CD8(+) T cell development influences repertoire selection.

  18. Interpretative repertoires that shape low-income African American women's reproductive health care seeking: "don't want to know" and "taking charge of your health".

    Science.gov (United States)

    Golden, Annis G; Pomerantz, Anita

    2015-01-01

    In the context of reproductive and sexual health, African American women have higher incidence of disease and poorer outcomes on key indicators when compared with White women. In this study, we used discourse analysis to identify and examine the workings of two clusters of interpretive resources ("interpretative repertoires") associated with reproductive/sexual health care seeking among low-income African American women who participated in semistructured interviews as part of a health promotion initiative. Interpretative repertoires are ways of accounting for engaging in or refraining from engaging in actions, which are shared by people in a community. We labeled the two interpretative repertoires "Don't Want to Know," and "Take Charge of Your Health." Within the "Don't Want to Know" repertoire, that testing would lead to threatening findings was assumed, a chain of devastating consequences was imagined, and a preference for uncertainty over certain knowledge was expressed. Conversely, the "Take Charge of Your Health" repertoire valued certainty over uncertainty, though in both interpretive frameworks, knowledge-based and emotion-based decision-making were intertwined. We conclude that health promotion initiatives--if they are to succeed in encouraging women to obtain valuable preventive health care services--must respond, in their choices of language and outreach strategies, to the expressed dilemma of wishing for reassurance but fearing bad news, to the intertwining of emotional reasoning and technorationality in health decision making, and to the particular relational experiences of African American women. Failure to do so will contribute to the continuation of reproductive and sexual health disparities.

  19. Tracking time-varying coefficient-functions

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Joensen, Alfred K.;

    2000-01-01

    is a combination of recursive least squares with exponential forgetting and local polynomial regression. It is argued, that it is appropriate to let the forgetting factor vary with the value of the external signal which is the argument of the coefficient functions. Some of the key properties of the modified method......, but otherwise unknown, functions of a low-dimensional input process. These coefficient functions are estimated adaptively and recursively without specifying a global parametric, form, i.e. the method allows for online tracking of the coefficient functions. Essentially, in its most simple form, the method...

  20. Tracking Time-Varying Coefficient-Functions

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Joensen, Alfred K.;

    1999-01-01

    of recursive least squares with exponential forgetting and local polynomial regression. However, it is argued, that it is appropriate to let the forgetting factor vary with the value of the external signal shich is argument of the coeffieient-functions.The properties of the modified method are sutdied......A conditional parametric ARX-model is an ARX-model in which the parameters re replaced by smooth functions of an, possibly multivariate, externalinput signal. These functions are called coefficient functions is suggested. Essentially, in its most simple form, this method is a combination...