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Sample records for parallel clonal microcultures

  1. Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytes.

    PubMed

    Fortunel, Nicolas O; Cadio, Emmanuelle; Vaigot, Pierre; Chadli, Loubna; Moratille, Sandra; Bouet, Stéphan; Roméo, Paul-Henri; Martin, Michèle T

    2010-04-01

    The basal layer of human epidermis contains both stem cells and keratinocyte progenitors. Because of this cellular heterogeneity, the development of methods suitable for investigations at a clonal level is dramatically needed. Here, we describe a new method that allows multi-parallel clonal cultures of basal keratinocytes. Immediately after extraction from tissue samples, cells are sorted by flow cytometry based on their high integrin-alpha 6 expression and plated individually in microculture wells. This automated cell deposition process enables large-scale characterization of primary clonogenic capacities. The resulting clonal growth profile provided a precise assessment of basal keratinocyte hierarchy, as the size distribution of 14-day-old clones ranged from abortive to highly proliferative clones containing 1.7 x 10(5) keratinocytes (17.4 cell doublings). Importantly, these 14-day-old primary clones could be used to generate three-dimensional reconstructed epidermis with the progeny of a single cell. In long-term cultures, a fraction of highly proliferative clones could sustain extensive expansion of >100 population doublings over 14 weeks and exhibited long-term epidermis reconstruction potency, thus fulfilling candidate stem cell functional criteria. In summary, parallel clonal microcultures provide a relevant model for single-cell studies on interfollicular keratinocytes, which could be also used in other epithelial models, including hair follicle and cornea. The data obtained using this system support the hierarchical model of basal keratinocyte organization in human interfollicular epidermis.

  2. Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma

    PubMed Central

    Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. PMID:26336987

  3. Microcultures and Informal Learning: A Heuristic Guiding Analysis of Conditions for Informal Learning in Local Higher Education Workplaces

    ERIC Educational Resources Information Center

    Roxå, Torgny; Mårtensson, Katarina

    2015-01-01

    This article contributes to knowledge about learning in workgroups, so called "microcultures" in higher education. It argues that socially constructed and institutionalised traditions, recurrent practices, and tacit assumptions in the various microcultures influence academic teachers towards certain behaviour. In line with this…

  4. The Transmission and Evolution of Experimental Microcultures in Groups of Young Children

    ERIC Educational Resources Information Center

    Whiten, Andrew; Flynn, Emma

    2010-01-01

    A new experimental microculture approach was developed to investigate the creation and transmission of differing traditions in small communities of young children. Four playgroups, with a total of 88 children, participated. In each of 2 playgroups, a single child was shown how to use 1 of 2 alternative methods of tool use, "lift" or "poke," to…

  5. A simple micro-culture method for the study of group B arboviruses*

    PubMed Central

    de Madrid, Ana Teresa; Porterfield, James S.

    1969-01-01

    Thirty-nine group B arboviruses have been titrated by a simple micro-culture method. The technique uses a stable line of pig kidney cells (PS cells) in which plaques develop when cells are first infected in suspension in the wells of haemagglutination trays and are then incubated for from 3 to 10 days under an overlay containing carboxymethyl-cellulose. This method can be adapted to measure neutralizing antibodies, and the principle underlying the test is applicable to other cells and other viruses. ImagesFIG. 1FIG. 2FIG. 3FIG. 4 PMID:4183812

  6. APPLICATION OF A NEW MICROCULTURING TECHNIQUE TO ASSESS THE EFFECTS OF TEMPERATURE AND SALINITY ON SPECIFIC GROWTH RATES OF SIX SYMBIODINIUM ISOLATES

    EPA Science Inventory

    A simple micro-culturing technique is described for determining specific growth rates of cultured Symbiodinium spp. Micro-cultures were prepared by transferring 200 L fresh test medium containing 2–10 Symbiodinium cells to wells of a flat bottom 96-well plate. Cultures were incub...

  7. Streptomycetes in micro-cultures: growth, production of secondary metabolites, and storage and retrieval in the 96-well format.

    PubMed

    Minas, W; Bailey, J E; Duetz, W

    2000-12-01

    Mycelium-forming Streptomyces strains were grown in one milliliter liquid micro-cultures in square deep-well microtiter plates. Growth was evaluated with respect to biomass formation and production of secondary metabolites which were found to be very similar in the micro-cultures, bioreactor, and shake flask cultivations, respectively. Despite repetitive sampling and extensive growth on the walls of the wells, no cross contamination occurred. Furthermore, we successfully employed cold storage at -20 degrees C of spore suspensions (in the 96-well format), directly prepared from cultures grown on agar in the microtitre plate. Cultures were retrieved by replicating aliquots from the frozen spore suspensions.

  8. Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing.

    PubMed

    McCracken, Joselle M; Badea, Adina; Kandel, Mikhail E; Gladman, A Sydney; Wetzel, David J; Popescu, Gabriel; Lewis, Jennifer A; Nuzzo, Ralph G

    2016-05-01

    3D hydrogel scaffolds are widely used in cellular microcultures and tissue engineering. Using direct ink writing, microperiodic poly(2-hydroxyethyl-methacrylate) (pHEMA) scaffolds are created that are then printed, cured, and modified by absorbing 30 kDa protein poly-l-lysine (PLL) to render them biocompliant in model NIH/3T3 fibroblast and MC3T3-E1 preosteoblast cell cultures. Spatial light interference microscopy (SLIM) live cell imaging studies are carried out to quantify cellular motilities for each cell type, substrate, and surface treatment of interest. 3D scaffold mechanics is investigated using atomic force microscopy (AFM), while their absorption kinetics are determined by confocal fluorescence microscopy (CFM) for a series of hydrated hydrogel films prepared from prepolymers with different homopolymer-to-monomer (Mr ) ratios. The observations reveal that the inks with higher Mr values yield relatively more open-mesh gels due to a lower degree of entanglement. The biocompatibility of printed hydrogel scaffolds can be controlled by both PLL content and hydrogel mesh properties.

  9. Clonal reproduction in fungi

    PubMed Central

    Taylor, John W.; Hann-Soden, Christopher; Branco, Sara; Sylvain, Iman; Ellison, Christopher E.

    2015-01-01

    Research over the past two decades shows that both recombination and clonality are likely to contribute to the reproduction of all fungi. This view of fungi is different from the historical and still commonly held view that a large fraction of fungi are exclusively clonal and that some fungi have been exclusively clonal for hundreds of millions of years. Here, we first will consider how these two historical views have changed. Then we will examine the impact on fungal research of the concept of restrained recombination [Tibayrenc M, Ayala FJ (2012) Proc Natl Acad Sci USA 109 (48):E3305–E3313]. Using animal and human pathogenic fungi, we examine extrinsic restraints on recombination associated with bottlenecks in genetic variation caused by geographic dispersal and extrinsic restraints caused by shifts in reproductive mode associated with either disease transmission or hybridization. Using species of the model yeast Saccharomyces and the model filamentous fungus Neurospora, we examine intrinsic restraints on recombination associated with mating systems that range from strictly clonal at one extreme to fully outbreeding at the other and those that lie between, including selfing and inbreeding. We also consider the effect of nomenclature on perception of reproductive mode and a means of comparing the relative impact of clonality and recombination on fungal populations. Last, we consider a recent hypothesis suggesting that fungi thought to have the most severe intrinsic constraints on recombination actually may have the fewest. PMID:26195774

  10. Effects of patch contrast and arrangement on benefits of clonal integration in a rhizomatous clonal plant

    PubMed Central

    Wang, Yong-Jian; Shi, Xue-Ping; Wu, Xiao-Jing; Meng, Xue-Feng; Wang, Peng-Cheng; Zhou, Zhi-Xiang; Luo, Fang-Li; Yu, Fei-Hai

    2016-01-01

    The availabilities of light and soil water resources usually spatially co-vary in natural habitats, and the spatial pattern of such co-variation may affect the benefits of physiological integration between connected ramets of clonal plants. In a greenhouse experiment, we grew connected or disconnected ramet pairs [consisting of a proximal (relatively old) and a distal (relative young) ramet] of a rhizomatous herb Iris japonica in four heterogeneous environments differing in patch arrangement (reciprocal vs. parallel patchiness of light and soil water) and patch contrast (high vs. low contrast of light and water). Biomass of the proximal part, distal part and clonal fragment of I. japonica were all significantly greater in the intact than in the severed treatment, in the parallel than in the reciprocal patchiness treatment and in the high than in the low contrast treatment, but the effect of severing the connection between ramet pairs did not depend on patch arrangement or contrast. Severing the connection decreased number of ramets of the distal part and the clonal fragment in the parallel patchiness arrangement, but not in the reciprocal patchiness arrangement. Therefore, the spatial arrangement of resource patches can alter the effects of clonal integration on asexual reproduction in I. japonica. PMID:27759040

  11. How clonal are Neisseria species? The epidemic clonality model revisited.

    PubMed

    Tibayrenc, Michel; Ayala, Francisco J

    2015-07-21

    The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria lactamica are often regarded as highly recombining bacteria. N. meningitidis has been considered a paradigmatic case of the "semiclonal model" or of "epidemic clonality," demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N. meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (i) the proposed way to distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N. meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model.

  12. The population genetics of clonal and partially clonal diploids.

    PubMed Central

    Balloux, François; Lehmann, Laurent; de Meeûs, Thierry

    2003-01-01

    The consequences of variable rates of clonal reproduction on the population genetics of neutral markers are explored in diploid organisms within a subdivided population (island model). We use both analytical and stochastic simulation approaches. High rates of clonal reproduction will positively affect heterozygosity. As a consequence, nearly twice as many alleles per locus can be maintained and population differentiation estimated as F(ST) value is strongly decreased in purely clonal populations as compared to purely sexual ones. With increasing clonal reproduction, effective population size first slowly increases and then points toward extreme values when the reproductive system tends toward strict clonality. This reflects the fact that polymorphism is protected within individuals due to fixed heterozygosity. Contrarily, genotypic diversity smoothly decreases with increasing rates of clonal reproduction. Asexual populations thus maintain higher genetic diversity at each single locus but a lower number of different genotypes. Mixed clonal/sexual reproduction is nearly indistinguishable from strict sexual reproduction as long as the proportion of clonal reproduction is not strongly predominant for all quantities investigated, except for genotypic diversities (both at individual loci and over multiple loci). PMID:12930767

  13. Effects of potassium sorbate and other antibotulinal agents on germination and outgrowth of Clostridium botulinum type E spores in microcultures.

    PubMed Central

    Seward, R A; Deibel, R H; Lindsay, R C

    1982-01-01

    The effects of potassium sorbate, sodium hypophosphite, sodium tripolyphosphate, sodium nitrite, and linoleic acid on the germination and outgrowth of Clostridium botulinum type E spores were studied in microcultures. At pH 5.8 to 6.0 in liver veal agar, the germination rate was decreased to nearly zero with 1.0, 1.5, or 2.0% sorbate. At pH 7.0 t 7.2, these levels of sorbate afforded germination and outgrowth of abnormally shaped cells that were defective in cell division. At the high pH range, 0.5 or 1.0% hypophosphite had effects similar to those of sorbate. The use of 0.05% sodium nitrite with sorbate enhanced the lysis of outgrowing cells at pH 7.2 or lower. Emergence and elongation were inhibited by 0.05% linoleic acid with or without 1.0% sorbate at pH 7.0 to 7.2. The addition of 0.5% tripolyphosphate to media containing 1.5% sorbate at pH 7.1 prevented normal cell growth to an extent greater than with sorbate alone. Images PMID:6758699

  14. Utility of the microculture method for Leishmania detection in non-invasive samples obtained from a blood bank.

    PubMed

    Ates, Sezen Canim; Bagirova, Malahat; Allahverdiyev, Adil M; Kocazeybek, Bekir; Kosan, Erdogan

    2013-10-01

    In recent years, the role of donor blood has taken an important place in epidemiology of Leishmaniasis. According to the WHO, the numbers of patients considered as symptomatic are only 5-20% of individuals with asymptomatic leishmaniasis. In this study for detection of Leishmania infection in donor blood samples, 343 samples from the Capa Red Crescent Blood Center were obtained and primarily analyzed by microscopic and serological methods. Subsequently, the traditional culture (NNN), Immuno-chromatographic test (ICT) and Polymerase Chain Reaction (PCR) methods were applied to 21 samples which of them were found positive with at least one method. Buffy coat (BC) samples from 343 blood donors were analyzed: 15 (4.3%) were positive by a microculture method (MCM); and 4 (1.1%) by smear. The sera of these 343 samples included 9 (2.6%) determined positive by ELISA and 7 (2%) positive by IFAT. Thus, 21 of (6.1%) the 343 subjects studied by smear, MCM, IFAT and ELISA techniques were identified as positive for leishmaniasis at least one of the techniques and the sensitivity assessed. According to our data, the sensitivity of the methods are identified as MCM (71%), smear (19%), IFAT (33%), ELISA (42%), NNN (4%), PCR (14%) and ICT (4%). Thus, with this study for the first time, the sensitivity of a MCM was examined in blood donors by comparing MCM with the methods used in the diagnosis of leishmaniasis. As a result, MCM was found the most sensitive method for detection of Leishmania parasites in samples obtained from a blood bank. In addition, the presence of Leishmania parasites was detected in donor bloods in Istanbul, a non-endemic region of Turkey, and these results is a vital importance for the health of blood recipients.

  15. How clonal are Neisseria species? The epidemic clonality model revisited

    PubMed Central

    Tibayrenc, Michel; Ayala, Francisco J.

    2015-01-01

    The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria lactamica are often regarded as highly recombining bacteria. N. meningitidis has been considered a paradigmatic case of the “semiclonal model” or of “epidemic clonality,” demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N. meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (i) the proposed way to distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N. meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model. PMID:26195766

  16. The clonal origin and clonal evolution of epithelial tumours

    PubMed Central

    Garcia, Sergio Britto; Novelli, Marco; Wright, Nicholas A

    2000-01-01

    While the origin of tumours, whether from one cell or many, has been a source of fascination for experimental oncologists for some time, in recent years there has been a veritable explosion of information about the clonal architecture of tumours and their antecedents, stimulated, in the main, by the ready accessibility of new molecular techniques. While most of these new results have apparently confirmed the monoclonal origin of human epithelial (and other) tumours, there are a significant number of studies in which this conclusion just cannot be made. Moreover, analysis of many articles show that the potential impact of such considerations as patch size and clonal evolution on determinations of clonality have largely been ignored, with the result that a number of these studies are confounded. However, the clonal architecture of preneoplastic lesions provide some interesting insights — many lesions which might have been hitherto regarded as hyperplasias are apparently clonal in derivation. If this is indeed true, it calls into some question our hopeful corollary that a monoclonal origin presages a neoplastic habitus. Finally, it is clear, for many reasons, that methods of analysis which involve the disaggregation of tissues, albeit microdissected, are far from ideal and we should be putting more effort into techniques where the clonal architecture of normal tissues, preneoplastic and preinvasive lesions and their derivative tumours can be directly visualized in situ. PMID:10762440

  17. Clonality-climate relationships along latitudinal gradient across China: adaptation of clonality to environments.

    PubMed

    Ye, Duo; Hu, Yukun; Song, Minghua; Pan, Xu; Xie, Xiufang; Liu, Guofang; Ye, Xuehua; Dong, Ming

    2014-01-01

    Plant clonality, the ability of a plant species to reproduce itself vegetatively through ramets (shoot-root units), occurs in many plant species and is considered to be more frequent in cold or wet environments. However, a deeper understanding on the clonality-climate relationships along large geographic gradients is still scarce. In this study we revealed the clonality-climate relationships along latitudinal gradient of entire China spanning from tropics to temperate zones using clonality data for 4015 vascular plant species in 545 terrestrial communities. Structural equation modeling (SEM) showed that, in general, the preponderance of clonality increased along the latitudinal gradient towards cold, dry or very wet environments. However, the distribution of clonality in China was significantly but only weakly correlated with latitude and four climatic factors (mean annual temperature, temperature seasonality, mean annual precipitation, precipitation seasonality). Clonality of woody and herbaceous species had opposite responses to climatic variables. More precisely, woody clonality showed higher frequency in wet or climatically stable environments, while herbaceous clonality preferred cold, dry or climatically instable environments. Unexplained variation in clonality may be owed to the influences of other environmental conditions and to different clonal strategies and underlying traits adopted by different growth forms and phylogenetic lineages. Therefore, in-depth research in terms of more detailed clonal growth form, phylogeny and additional environmental variables are encouraged to further understand plant clonality response to climatic and/or edaphic conditions.

  18. Influences of clonality on plant sexual reproduction

    PubMed Central

    Barrett, Spencer C. H.

    2015-01-01

    Flowering plants possess an unrivaled diversity of mechanisms for achieving sexual and asexual reproduction, often simultaneously. The commonest type of asexual reproduction is clonal growth (vegetative propagation) in which parental genotypes (genets) produce vegetative modules (ramets) that are capable of independent growth, reproduction, and often dispersal. Clonal growth leads to an expansion in the size of genets and increased fitness because large floral displays increase fertility and opportunities for outcrossing. Moreover, the clonal dispersal of vegetative propagules can assist “mate finding,” particularly in aquatic plants. However, there are ecological circumstances in which functional antagonism between sexual and asexual reproductive modes can negatively affect the fitness of clonal plants. Populations of heterostylous and dioecious species have a small number of mating groups (two or three), which should occur at equal frequency in equilibrium populations. Extensive clonal growth and vegetative dispersal can disrupt the functioning of these sexual polymorphisms, resulting in biased morph ratios and populations with a single mating group, with consequences for fertility and mating. In populations in which clonal propagation predominates, mutations reducing fertility may lead to sexual dysfunction and even the loss of sex. Recent evidence suggests that somatic mutations can play a significant role in influencing fitness in clonal plants and may also help explain the occurrence of genetic diversity in sterile clonal populations. Highly polymorphic genetic markers offer outstanding opportunities for gaining novel insights into functional interactions between sexual and clonal reproduction in flowering plants. PMID:26195747

  19. How Clonal Is Staphylococcus aureus?

    PubMed Central

    Feil, Edward J.; Cooper, Jessica E.; Grundmann, Hajo; Robinson, D. Ashley; Enright, Mark C.; Berendt, Tony; Peacock, Sharon J.; Smith, John Maynard; Murphy, Michael; Spratt, Brian G.; Moore, Catrin E.; Day, Nicholas P. J.

    2003-01-01

    Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable “core” genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow. PMID:12754228

  20. Competitive equivalence maintains persistent inter-clonal boundaries.

    PubMed

    Ferrell, David L

    2005-01-01

    Clear boundaries often separate adjacent conspecific competitors. These boundaries may reflect bordering animal territories or regions of inter-organism contact in mobile and non-mobile organisms, respectively. Sessile, clonal organisms often form persistent inter-clonal boundaries despite great variation in competitive ability among genotypes within a population. I show that neighboring clones in the sea anemone Anthopleura elegantissima and three species of the marine hydroid genus Hydractinia are more evenly matched in terms of competitive ability than expected by chance. Hypotheses of genetic relatedness or similar environmental regime shared by neighboring clones are inconsistent with the observed similarities between adjacent competitors in one or both taxa. Instead, inter-clonal borders evidently persist as standoffs between evenly matched competitors. Large differences in competitive ability between bordering clones were rarely observed, suggesting that dominant clones quickly displace or eliminate others in competitive mismatches. This ecological parallel between taxa (i.e., competitive equivalence) exists despite several fundamental differences (e.g., geographical distribution, habitat, body size, longevity), suggesting that competitive equivalence may be a widespread determinant of boundary persistence between adjacent competitors.

  1. Clonality as a driver of spatial genetic structure in populations of clonal tree species.

    PubMed

    Dering, Monika; Chybicki, Igor Jerzy; Rączka, Grzegorz

    2015-09-01

    Random genetic drift, natural selection and restricted gene dispersal are basic factors of the spatial genetic structure (SGS) in plant populations. Clonal reproduction has a profound effect on population dynamics and genetic structure and thus emerges as a potential factor in contributing to and modelling SGS. In order to assess the impact of clonality on SGS we studied clonal structure and SGS in the population of Populus alba. Six hundred and seventy-two individuals were mapped and genotyped with 16 nuclear microsatellite markers. To answer the more general question regarding the relationship between SGS and clonality we used Sp statistics, which allows for comparisons of the extent of SGS among different studies, and the comparison of published data on SGS in clonal and non-clonal tree species. Sp statistic was extracted for 14 clonal and 27 non-clonal species belonging to 7 and 18 botanical families, respectively. Results of genetic investigations conducted in the population of P. alba showed over-domination of clonal reproduction, which resulted in very low clonal diversity (R = 0.12). Significant SGS was found at both ramet (Sp = 0.095) and genet level (Sp = 0.05) and clonal reproduction was indicated as an important but not sole driving factor of SGS. Within-population structure, probably due to family structure also contributed to high SGS. High mean dominance index (D = 0.82) indicated low intermingling among genets. Literature survey revealed that clonal tree species significantly differ from non-clonal species with respect to SGS, having 2.8-fold higher SGS. This led us to conclude that clonality is a life-history trait that can have deep impact on processes acting in populations of clonal tree species leading to significant SGS.

  2. Ecological Consequences of Clonal Integration in Plants

    PubMed Central

    Liu, Fenghong; Liu, Jian; Dong, Ming

    2016-01-01

    Clonal plants are widespread throughout the plant kingdom and dominate in diverse habitats. Spatiotemporal heterogeneity of environment is pervasive at multiple scales, even at scales relevant to individual plants. Clonal integration refers to resource translocation and information communication among the ramets of clonal plants. Due to clonal integration, clonal plant species possess a series of peculiar attributes: plasticity in response to local and non-local conditions, labor division with organ specialization for acquiring locally abundant resources, foraging behavior by selective placement of ramets in resource-rich microhabitats, and avoidance of intraclonal competition. Clonal integration has very profound ecological consequences for clonal plants. It allows them to efficiently cope with environmental heterogeneity, by alleviating local resource shortages, buffering environmental stresses and disturbances, influencing competitive ability, increasing invasiveness, and altering species composition and invasibility at the community level. In this paper, we present a comprehensive review of research on the ecological consequences of plant clonal integration based on a large body of literature. We also attempt to propose perspectives for future research. PMID:27446093

  3. Clonal selection versus clonal cooperation: the integrated perception of immune objects

    PubMed Central

    Nataf, Serge

    2016-01-01

    Analogies between the immune and nervous systems were first envisioned by the immunologist Niels Jerne who introduced the concepts of antigen "recognition" and immune "memory". However, since then, it appears that only the cognitive immunology paradigm proposed by Irun Cohen, attempted to further theorize the immune system functions through the prism of neurosciences. The present paper is aimed at revisiting this analogy-based reasoning. In particular, a parallel is drawn between the brain pathways of visual perception and the processes allowing the global perception of an "immune object". Thus, in the visual system, distinct features of a visual object (shape, color, motion) are perceived separately by distinct neuronal populations during a primary perception task. The output signals generated during this first step instruct then an integrated perception task performed by other neuronal networks. Such a higher order perception step is by essence a cooperative task that is mandatory for the global perception of visual objects. Based on a re-interpretation of recent experimental data, it is suggested that similar general principles drive the integrated perception of immune objects in secondary lymphoid organs (SLOs). In this scheme, the four main categories of signals characterizing an immune object (antigenic, contextual, temporal and localization signals) are first perceived separately by distinct networks of immunocompetent cells.  Then, in a multitude of SLO niches, the output signals generated during this primary perception step are integrated by TH-cells at the single cell level. This process eventually generates a multitude of T-cell and B-cell clones that perform, at the scale of SLOs, an integrated perception of immune objects. Overall, this new framework proposes that integrated immune perception and, consequently, integrated immune responses, rely essentially on clonal cooperation rather than clonal selection. PMID:27830060

  4. Clonal growth and plant species abundance

    PubMed Central

    Herben, Tomáš; Nováková, Zuzana; Klimešová, Jitka

    2014-01-01

    Background and Aims Both regional and local plant abundances are driven by species' dispersal capacities and their abilities to exploit new habitats and persist there. These processes are affected by clonal growth, which is difficult to evaluate and compare across large numbers of species. This study assessed the influence of clonal reproduction on local and regional abundances of a large set of species and compared the predictive power of morphologically defined traits of clonal growth with data on actual clonal growth from a botanical garden. The role of clonal growth was compared with the effects of seed reproduction, habitat requirements and growth, proxied both by LHS (leaf–height–seed) traits and by actual performance in the botanical garden. Methods Morphological parameters of clonal growth, actual clonal reproduction in the garden and LHS traits (leaf-specific area – height – seed mass) were used as predictors of species abundance, both regional (number of species records in the Czech Republic) and local (mean species cover in vegetation records) for 836 perennial herbaceous species. Species differences in habitat requirements were accounted for by classifying the dataset by habitat type and also by using Ellenberg indicator values as covariates. Key Results After habitat differences were accounted for, clonal growth parameters explained an important part of variation in species abundance, both at regional and at local levels. At both levels, both greater vegetative growth in cultivation and greater lateral expansion trait values were correlated with higher abundance. Seed reproduction had weaker effects, being positive at the regional level and negative at the local level. Conclusions Morphologically defined traits are predictive of species abundance, and it is concluded that simultaneous investigation of several such traits can help develop hypotheses on specific processes (e.g. avoidance of self-competition, support of offspring) potentially

  5. Clonal Integration Enhances the Performance of a Clonal Plant Species under Soil Alkalinity Stress

    PubMed Central

    Sun, Juanjuan; Chen, Jishan; Zhang, Yingjun

    2015-01-01

    Clonal plants have been shown to successfully survive in stressful environments, including salinity stress, drought and depleted nutrients through clonal integration between original and subsequent ramets. However, relatively little is known about whether clonal integration can enhance the performance of clonal plants under alkalinity stress. We investigated the effect of clonal integration on the performance of a typical rhizomatous clonal plant, Leymus chinensis, using a factorial experimental design with four levels of alkalinity and two levels of rhizome connection treatments, connected (allowing integration) and severed (preventing integration). Clonal integration was estimated by comparing physiological and biomass features between the rhizome-connected and rhizome-severed treatments. We found that rhizome-connected treatment increased the biomass, height and leaf water potential of subsequent ramets at highly alkalinity treatments but did not affect them at low alkalinity treatments. However, rhizome-connected treatment decreased the root biomass of subsequent ramets and did not influence the photosynthetic rates of subsequent ramets. The biomass of original ramets was reduced by rhizome-connected treatment at the highest alkalinity level. These results suggest that clonal integration can increase the performance of clonal plants under alkalinity stress. Rhizome-connected plants showed dramatically increased survival of buds with negative effects on root weight, indicating that clonal integration influenced the resource allocation pattern of clonal plants. A cost-benefit analysis based on biomass measures showed that original and subsequent ramets significantly benefited from clonal integration in highly alkalinity stress, indicating that clonal integration is an important adaptive strategy by which clonal plants could survive in local alkalinity soil. PMID:25790352

  6. Clonal integration enhances the performance of a clonal plant species under soil alkalinity stress.

    PubMed

    Zhang, Wenjun; Yang, Gaowen; Sun, Juanjuan; Chen, Jishan; Zhang, Yingjun

    2015-01-01

    Clonal plants have been shown to successfully survive in stressful environments, including salinity stress, drought and depleted nutrients through clonal integration between original and subsequent ramets. However, relatively little is known about whether clonal integration can enhance the performance of clonal plants under alkalinity stress. We investigated the effect of clonal integration on the performance of a typical rhizomatous clonal plant, Leymus chinensis, using a factorial experimental design with four levels of alkalinity and two levels of rhizome connection treatments, connected (allowing integration) and severed (preventing integration). Clonal integration was estimated by comparing physiological and biomass features between the rhizome-connected and rhizome-severed treatments. We found that rhizome-connected treatment increased the biomass, height and leaf water potential of subsequent ramets at highly alkalinity treatments but did not affect them at low alkalinity treatments. However, rhizome-connected treatment decreased the root biomass of subsequent ramets and did not influence the photosynthetic rates of subsequent ramets. The biomass of original ramets was reduced by rhizome-connected treatment at the highest alkalinity level. These results suggest that clonal integration can increase the performance of clonal plants under alkalinity stress. Rhizome-connected plants showed dramatically increased survival of buds with negative effects on root weight, indicating that clonal integration influenced the resource allocation pattern of clonal plants. A cost-benefit analysis based on biomass measures showed that original and subsequent ramets significantly benefited from clonal integration in highly alkalinity stress, indicating that clonal integration is an important adaptive strategy by which clonal plants could survive in local alkalinity soil.

  7. How clonal are human mitochondria?

    PubMed Central

    Eyre-Walker, A; Smith, N H; Smith, J M

    1999-01-01

    Phylogenetic trees constructed using human mitochondrial sequences contain a large number of homoplasies. These are due either to repeated mutation or to recombination between mitochondrial lineages. We show that a tree constructed using synonymous variation in the protein coding sequences of 29 largely complete human mitochondrial molecules contains 22 homoplasies at 32 phylogenetically informative sites. This level of homoplasy is very unlikely if inheritance is clonal, even if we take into account base composition bias. There must either be 'hypervariable' sites or recombination between mitochondria. We present evidence which suggests that hypervariable sites do not exist in our data. It therefore seems likely that recombination has occurred between mitochondrial lineages in humans. PMID:10189711

  8. Enforced Clonality Confers a Fitness Advantage

    PubMed Central

    Martínková, Jana; Klimešová, Jitka

    2016-01-01

    In largely clonal plants, splitting of a maternal plant into potentially independent plants (ramets) is usually spontaneous; however, such fragmentation also occurs in otherwise non-clonal species due to application of external force. This process might play an important yet largely overlooked role for otherwise non-clonal plants by providing a mechanism to regenerate after disturbance. Here, in a 5-year garden experiment on two short-lived, otherwise non-clonal species, Barbarea vulgaris and Barbarea stricta, we compared the fitness of plants fragmented by simulated disturbance (“enforced ramets”) both with plants that contemporaneously originate in seed and with individuals unscathed by the disturbance event. Because the ability to regrow from fragments is related to plant age and stored reserves, we compared the effects of disturbance applied during three different ontogenetic stages of the plants. In B. vulgaris, enforced ramet fitness was higher than the measured fitness values of both uninjured plants and plants established from seed after the disturbance. This advantage decreased with increasing plant age at the time of fragmentation. In B. stricta, enforced ramet fitness was lower than or similar to fitness of uninjured plants and plants grown from seed. Our results likely reflect the habitat preferences of the study species, as B. vulgaris occurs in anthropogenic, disturbed habitats where body fragmentation is more probable and enforced clonality thus more advantageous than in the more natural habitats preferred by B. stricta. Generalizing from our results, we see that increased fitness yielded by enforced clonality would confer an evolutionary advantage in the face of disturbance, especially in habitats where a seed bank has not been formed, e.g., during invasion or colonization. Our results thus imply that enforced clonality should be taken into account when studying population dynamics and life strategies of otherwise non-clonal species in disturbed

  9. Enhancing cancer clonality analysis with integrative genomics

    PubMed Central

    2015-01-01

    Introduction It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. Methods Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. Results Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. Conclusion The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational

  10. Advances for Studying Clonal Evolution in Cancer

    PubMed Central

    Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

    2013-01-01

    The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

  11. Phenotypic plasticity and specialization in clonal versus non-clonal plants: A data synthesis

    NASA Astrophysics Data System (ADS)

    Fazlioglu, Fatih; Bonser, Stephen P.

    2016-11-01

    Reproductive strategies can be associated with ecological specialization and generalization. Clonal plants produce lineages adapted to the maternal habitat that can lead to specialization. However, clonal plants frequently display high phenotypic plasticity (e.g. clonal foraging for resources), factors linked to ecological generalization. Alternately, sexual reproduction can be associated with generalization via increasing genetic variation or specialization through rapid adaptive evolution. Moreover, specializing to high or low quality habitats can determine how phenotypic plasticity is expressed in plants. The specialization hypothesis predicts that specialization to good environments results in high performance trait plasticity and specialization to bad environments results in low performance trait plasticity. The interplay between reproductive strategies, phenotypic plasticity, and ecological specialization is important for understanding how plants adapt to variable environments. However, we currently have a poor understanding of these relationships. In this study, we addressed following questions: 1) Is there a relationship between phenotypic plasticity, specialization, and reproductive strategies in plants? 2) Do good habitat specialists express greater performance trait plasticity than bad habitat specialists? We searched the literature for studies examining plasticity for performance traits and functional traits in clonal and non-clonal plant species from different habitat types. We found that non-clonal (obligate sexual) plants expressed greater performance trait plasticity and functional trait plasticity than clonal plants. That is, non-clonal plants exhibited a specialist strategy where they perform well only in a limited range of habitats. Clonal plants expressed less performance loss across habitats and a more generalist strategy. In addition, specialization to good habitats did not result in greater performance trait plasticity. This result was

  12. Evolutionary perspectives on clonal reproduction in vertebrate animals.

    PubMed

    Avise, John C

    2015-07-21

    A synopsis is provided of different expressions of whole-animal vertebrate clonality (asexual organismal-level reproduction), both in the laboratory and in nature. For vertebrate taxa, such clonal phenomena include the following: human-mediated cloning via artificial nuclear transfer; intergenerational clonality in nature via parthenogenesis and gynogenesis; intergenerational hemiclonality via hybridogenesis and kleptogenesis; intragenerational clonality via polyembryony; and what in effect qualifies as clonal replication via self-fertilization and intense inbreeding by simultaneous hermaphrodites. Each of these clonal or quasi-clonal mechanisms is described, and its evolutionary genetic ramifications are addressed. By affording an atypical vantage on standard vertebrate reproduction, clonality offers fresh perspectives on the evolutionary and ecological significance of recombination-derived genetic variety.

  13. Evolutionary perspectives on clonal reproduction in vertebrate animals

    PubMed Central

    Avise, John C.

    2015-01-01

    A synopsis is provided of different expressions of whole-animal vertebrate clonality (asexual organismal-level reproduction), both in the laboratory and in nature. For vertebrate taxa, such clonal phenomena include the following: human-mediated cloning via artificial nuclear transfer; intergenerational clonality in nature via parthenogenesis and gynogenesis; intergenerational hemiclonality via hybridogenesis and kleptogenesis; intragenerational clonality via polyembryony; and what in effect qualifies as clonal replication via self-fertilization and intense inbreeding by simultaneous hermaphrodites. Each of these clonal or quasi-clonal mechanisms is described, and its evolutionary genetic ramifications are addressed. By affording an atypical vantage on standard vertebrate reproduction, clonality offers fresh perspectives on the evolutionary and ecological significance of recombination-derived genetic variety. PMID:26195735

  14. 'Sharpe', a clonal plum rootstock for peach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sharpe clonal rootstock for peach is jointly released for grower trial by the U.S. Department of Agriculture, Agricultural Research Service (Byron, GA), and Florida Agricultural Experiment Station. Sharpe, previously tested as FLA1-1, was discovered in the wild and appears to be a hybrid of Chickas...

  15. HIV genetic information and clonal growth

    Cancer.gov

    Based on an analysis of blood cells from five HIV-infected individuals, NCI researchers have identified more than 2,400 HIV DNA insertion sites. Analysis of these sites showed that there is extensive clonal expansion (growth) of HIV infected cells.

  16. Clonal Interference in the Evolution of Influenza

    PubMed Central

    Strelkowa, Natalja; Lässig, Michael

    2012-01-01

    The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: we find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza’s evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference. PMID:22851649

  17. Evaluating Clonal Expansion of HIV-Infected Cells: Optimization of PCR Strategies to Predict Clonality

    PubMed Central

    Laskey, Sarah B.; Pohlmeyer, Christopher W.; Bruner, Katherine M.; Siliciano, Robert F.

    2016-01-01

    In HIV-infected individuals receiving suppressive antiretroviral therapy, the virus persists indefinitely in a reservoir of latently infected cells. The proliferation of these cells may contribute to the stability of the reservoir and thus to the lifelong persistence of HIV-1 in infected individuals. Because the HIV-1 replication process is highly error-prone, the detection of identical viral genomes in distinct host cells provides evidence for the clonal expansion of infected cells. We evaluated alignments of unique, near-full-length HIV-1 sequences to determine the relationship between clonality in a short region and clonality in the full genome. Although it is common to amplify and sequence short, subgenomic regions of the viral genome for phylogenetic analysis, we show that sequence identity of these amplicons does not guarantee clonality across the full viral genome. We show that although longer amplicons capture more diversity, no subgenomic region can recapitulate the diversity of full viral genomes. Consequently, some identical subgenomic amplicons should be expected even from the analysis of completely unique viral genomes, and the presence of identical amplicons alone is not proof of clonally expanded HIV-1. We present a method for evaluating evidence of clonal expansion in the context of these findings. PMID:27494508

  18. Consequences of clonality for sexual fitness: Clonal expansion enhances fitness under spatially restricted dispersal

    PubMed Central

    Van Drunen, Wendy E.; van Kleunen, Mark; Dorken, Marcel E.

    2015-01-01

    Clonality is a pervasive feature of sessile organisms, but this form of asexual reproduction is thought to interfere with sexual fitness via the movement of gametes among the modules that comprise the clone. This within-clone movement of gametes is expected to reduce sexual fitness via mate limitation of male reproductive success and, in some cases, via the production of highly inbred (i.e., self-fertilized) offspring. However, clonality also results in the spatial expansion of the genetic individual (i.e., genet), and this should decrease distances gametes and sexually produced offspring must travel to avoid competing with other gametes and offspring from the same clone. The extent to which any negative effects of clonality on mating success might be offset by the positive effects of spatial expansion is poorly understood. Here, we develop spatially explicit models in which fitness was determined by the success of genets through their male and female sex functions. Our results indicate that clonality serves to increase sexual fitness when it is associated with the outward expansion of the genet. Our models further reveal that the main fitness benefit of clonal expansion might occur through the dispersal of offspring over a wider area compared with nonclonal phenotypes. We conclude that, instead of interfering with sexual reproduction, clonal expansion should often serve to enhance sexual fitness. PMID:26195748

  19. Long-term antibody synthesis in vitro. VI. Anti-allotype sera as probes of clonal products in affinity maturation.

    PubMed

    Conway de Macario, E; Macario, A J; Tosi, R M; Celada, F; Landucci-Tosi, S

    1978-08-01

    A new experimental system is described for measuring the allotypic product of rabbit B cells during long-lasting in vitro antibody responses. The immunoenzymatic assays described allow determination of several parameters mapping in different regions of the same molecule, which can be measured and combined to yield a multidimensional picture of the time-course dynamics of antibody synthesis. The rabbit immune system responding to Escherichia coli beta-D-galactosidase was sample and disassembled by (a) culturing lymph node microfragments and (b) sorting out from among all anti-enzyme antibodies only those activating a mutant enzyme, AMEF, which bore the b4 or b9 allotype. A considerable simplification of the response was achieved in the microcultures as documented by cultures of heterozygous cells which produced only one allotype and by the fact that each culture showed a distinctive pattern when antibody titre, association constant, heterogeneity index, L-chain type, and k-chain allotype were considered together. This array of patterns was not an artifact but the result of disassembling a representative sample of the rabbit immune system into small components, since the b4/b9 ratio obtained by averaging the results of all cultures from a heterozygous rabbit lymph node was the same as the serum ratio. Despite the Poisson distribution of the responder microcultures, none of them was monoclonal; i.e. no antibodies homogeneous by all parameters tested were observed, This finidng supports the notion that in normal lymphoid tissue in its native tridimensional arrangement, one T cell can trigger several B cells clustered in one antibody-forming unit. This natural arrangement would ensure the monospecificity of the cluster (dictated by the T cell) while allowing for variation in affinity (depending upon the array of B cells in the unit). Accordingly our findings would results from the fact that as the size of the microfragments was reduced, the cells diluted out first were

  20. Long-term antibody synthesis in vitro. VI. Anti-allotype sera as probes of clonal products in affinity maturation.

    PubMed Central

    Conway de Macario, E; Macario, A J; Tosi, R M; Celada, F; Landucci-Tosi, S

    1978-01-01

    A new experimental system is described for measuring the allotypic product of rabbit B cells during long-lasting in vitro antibody responses. The immunoenzymatic assays described allow determination of several parameters mapping in different regions of the same molecule, which can be measured and combined to yield a multidimensional picture of the time-course dynamics of antibody synthesis. The rabbit immune system responding to Escherichia coli beta-D-galactosidase was sample and disassembled by (a) culturing lymph node microfragments and (b) sorting out from among all anti-enzyme antibodies only those activating a mutant enzyme, AMEF, which bore the b4 or b9 allotype. A considerable simplification of the response was achieved in the microcultures as documented by cultures of heterozygous cells which produced only one allotype and by the fact that each culture showed a distinctive pattern when antibody titre, association constant, heterogeneity index, L-chain type, and k-chain allotype were considered together. This array of patterns was not an artifact but the result of disassembling a representative sample of the rabbit immune system into small components, since the b4/b9 ratio obtained by averaging the results of all cultures from a heterozygous rabbit lymph node was the same as the serum ratio. Despite the Poisson distribution of the responder microcultures, none of them was monoclonal; i.e. no antibodies homogeneous by all parameters tested were observed, This finidng supports the notion that in normal lymphoid tissue in its native tridimensional arrangement, one T cell can trigger several B cells clustered in one antibody-forming unit. This natural arrangement would ensure the monospecificity of the cluster (dictated by the T cell) while allowing for variation in affinity (depending upon the array of B cells in the unit). Accordingly our findings would results from the fact that as the size of the microfragments was reduced, the cells diluted out first were

  1. Determinants of Daphnia clonal diversity in lakes

    SciTech Connect

    Kolasa, J.; Mort, M.

    1987-07-01

    Populations of Daphnia show high clonal diversity in large lakes. Hypothetically, this diversity may be maintained by either intrinsic population mechanisms such as reproductive strategies or by structuring properties of habitat such as heterogeneity and associated scale differences. To discriminate between these two classes of factors the authors have applied a predictive hierarchichal model to clone data from 9 northern German lakes (46 clones; N=1236). The model operated reliably by using ecological ranges (a course measure of heterogeneity) of taxa. Concordance of observed patterns and predictions of the model would favor the heterogeneity hypothesis, while the opposite result would suggest greater influence of population-based mechanisms in explaining clonal diversity/abundance patterns. The results of their analysis point towards habitat heterogeneity as the dominant determinant of diversity and abundance structure of Daphnia populations in lakes.

  2. Parallel rendering

    NASA Technical Reports Server (NTRS)

    Crockett, Thomas W.

    1995-01-01

    This article provides a broad introduction to the subject of parallel rendering, encompassing both hardware and software systems. The focus is on the underlying concepts and the issues which arise in the design of parallel rendering algorithms and systems. We examine the different types of parallelism and how they can be applied in rendering applications. Concepts from parallel computing, such as data decomposition, task granularity, scalability, and load balancing, are considered in relation to the rendering problem. We also explore concepts from computer graphics, such as coherence and projection, which have a significant impact on the structure of parallel rendering algorithms. Our survey covers a number of practical considerations as well, including the choice of architectural platform, communication and memory requirements, and the problem of image assembly and display. We illustrate the discussion with numerous examples from the parallel rendering literature, representing most of the principal rendering methods currently used in computer graphics.

  3. Clonal Astrocytic Response to Cortical Injury

    PubMed Central

    Núñez-Llaves, Raúl; López-Mascaraque, Laura

    2013-01-01

    Astrocytes are a heterogeneous population of glial cells with multifaceted roles in the central nervous system. Recently, the new method for the clonal analysis Star Track evidenced the link between astrocyte heterogeneity and lineage. Here, we tested the morphological response to mechanical injury of clonally related astrocytes using the Star Track approach, which labels each cell lineage with a specific code of colors. Histological and immunohistochemical analyses at 7 days post injury revealed a variety of morphological changes that were different among distinct clones. In many cases, cells of the same clone responded equally to the injury, suggesting the dependence on their genetic codification (intrinsic response). However, in other cases cells of the same clone responded differently to the injury, indicating their response to extrinsic factors. Thus, whereas some clones exhibited a strong morphological alteration or a high proliferative response to the injury, other clones located at similar distances to the lesion were apparently unresponsive. Concurrence of different clonal responses to the injury reveals the importance of the development determining the astrocyte features in response to brain injuries. These features should be considered to develop therapies that affect glial function. PMID:24040158

  4. Differential Clonal Expansion in an Invading Cell Population: Clonal Advantage or Dumb Luck?

    PubMed

    Newgreen, Donald F; Zhang, Dongcheng; Cheeseman, Bevan L; Binder, Benjamin J; Landman, Kerry A

    2017-01-01

    In neoplastic cell growth, clones and subclones are variable both in size and mutational spectrum. The largest of these clones are believed to represent those cells with mutations that make them the most "fit," in a Darwinian sense, for expansion in their microenvironment. Thus, the degree of quantitative clonal expansion is regarded as being determined by innate qualitative differences between the cells that originate each clone. Here, using a combination of mathematical modelling and clonal labelling experiments applied to the developmental model system of the forming enteric nervous system, we describe how cells which are qualitatively identical may consistently produce clones of dramatically different sizes: most clones are very small while a few clones we term "superstars" contribute most of the cells to the final population. The basis of this is minor stochastic variations ("luck") in the timing and direction of movement and proliferation of individual cells, which builds a local advantage for daughter cells that is cumulative. This has potentially important consequences. In cancers, especially before strongly selective cytotoxic therapy, the assumption that the largest clones must be the cells with deterministic proliferative ability may not always hold true. In development, the gradual loss of clonal diversity as "superstars" take over the population may erode the resilience of the system to somatic mutations, which may have occurred early in clonal growth.

  5. The evidence for clonal spreading of quinolone resistance with a particular clonal complex of Campylobacter jejuni.

    PubMed

    Kovač, J; Cadež, N; Lušicky, M; Nielsen, E Møller; Ocepek, M; Raspor, P; Možina, S Smole

    2014-12-01

    Campylobacter is the most prevalent cause of bacterial gastroenteritis worldwide and it represents a significant public health risk of increasing severity due to its escalating resistance to clinically important quinolone and macrolide antibiotics. As a zoonotic pathogen Campylobacter is transmitted along the food chain and naturally cycles from environmental waters, feedstuff, animals and food to humans. We determined antibiotic resistance profiles, as well as multilocus sequence types and flaA-SVR types for 52 C. jejuni isolated in Slovenia from human, animal, raw and cured chicken meat and water samples. Twenty-eight different sequence types, arranged in ten clonal complexes, three new allele types and five new sequence types were identified, indicating the relatively high diversity in a small group of strains. The assignment of strains from different sources to the same clonal complexes indicates their transmission along the food supply chain. The most prevalent clonal complex was CC21, which was also the genetic group with 95% of quinolone-resistant strains. Based on the genetic relatedness of these quinolone-resistant strains identified by polymerase chain reaction with a mismatch amplification mutation assay and sequencing of the quinolone resistance-determining region of the gyrA gene, we conclude that the high resistance prevalence observed indicates the local clonal spread of quinolone resistance with CC21.

  6. Extensive clonal spread and extreme longevity in saw palmetto, a foundation clonal plant.

    PubMed

    Takahashi, Mizuki K; Horner, Liana M; Kubota, Toshiro; Keller, Nathan A; Abrahamson, Warren G

    2011-09-01

    The lack of effective tools has hampered out ability to assess the size, growth and ages of clonal plants. With Serenoa repens (saw palmetto) as a model, we introduce a novel analytical framework that integrates DNA fingerprinting and mathematical modelling to simulate growth and estimate ages of clonal plants. We also demonstrate the application of such life-history information of clonal plants to provide insight into management plans. Serenoa is an ecologically important foundation species in many Southeastern United States ecosystems; yet, many land managers consider Serenoa a troublesome invasive plant. Accordingly, management plans have been developed to reduce or eliminate Serenoa with little understanding of its life history. Using Amplified Fragment Length Polymorphisms, we genotyped 263 Serenoa and 134 Sabal etonia (a sympatric non-clonal palmetto) samples collected from a 20 × 20 m study plot in Florida scrub. Sabal samples were used to assign small field-unidentifiable palmettos to Serenoa or Sabal and also as a negative control for clone detection. We then mathematically modelled clonal networks to estimate genet ages. Our results suggest that Serenoa predominantly propagate via vegetative sprouts and 10,000-year-old genets may be common, while showing no evidence of clone formation by Sabal. The results of this and our previous studies suggest that: (i) Serenoa has been part of scrub associations for thousands of years, (ii) Serenoa invasion are unlikely and (ii) once Serenoa is eliminated from local communities, its restoration will be difficult. Reevaluation of the current management tools and plans is an urgent task.

  7. Parallel machines: Parallel machine languages

    SciTech Connect

    Iannucci, R.A. )

    1990-01-01

    This book presents a framework for understanding the tradeoffs between the conventional view and the dataflow view with the objective of discovering the critical hardware structures which must be present in any scalable, general-purpose parallel computer to effectively tolerate latency and synchronization costs. The author presents an approach to scalable general purpose parallel computation. Linguistic Concerns, Compiling Issues, Intermediate Language Issues, and hardware/technological constraints are presented as a combined approach to architectural Develoement. This book presents the notion of a parallel machine language.

  8. Clonality Testing in Veterinary Medicine: A Review With Diagnostic Guidelines.

    PubMed

    Keller, S M; Vernau, W; Moore, P F

    2016-07-01

    The accurate distinction of reactive and neoplastic lymphoid proliferations can present challenges. Given the different prognoses and treatment strategies, a correct diagnosis is crucial. Molecular clonality assays assess rearranged lymphocyte antigen receptor gene diversity and can help differentiate reactive from neoplastic lymphoid proliferations. Molecular clonality assays are commonly used to assess atypical, mixed, or mature lymphoid proliferations; small tissue fragments that lack architecture; and fluid samples. In addition, clonality testing can be utilized to track neoplastic clones over time or across anatomic sites. Molecular clonality assays are not stand-alone tests but useful adjuncts that follow clinical, morphologic, and immunophenotypic assessment. Even though clonality testing provides valuable information in a variety of situations, the complexities and pitfalls of this method, as well as its dependency on the experience of the interpreter, are often understated. In addition, a lack of standardized terminology, laboratory practices, and interpretational guidelines hinders the reproducibility of clonality testing across laboratories in veterinary medicine. The objectives of this review are twofold. First, the review is intended to familiarize the diagnostic pathologist or interested clinician with the concepts, potential pitfalls, and limitations of clonality testing. Second, the review strives to provide a basis for future harmonization of clonality testing in veterinary medicine by providing diagnostic guidelines.

  9. Clonal distribution and virulence of Campylobacter jejuni isolates in blood.

    PubMed

    Feodoroff, Benjamin; de Haan, Caroline P A; Ellström, Patrik; Sarna, Seppo; Hänninen, Marja-Liisa; Rautelin, Hilpi

    2013-10-01

    Campylobacter jejuni bacteria are highly diverse enteropathogens. Seventy-three C. jejuni isolates from blood collected in Finland were analyzed by multilocus sequence typing and serum resistance. Approximately half of the isolates belonged to the otherwise uncommon sequence type 677 clonal complex. Isolates of this clonal complex were more resistant than other isolates to human serum.

  10. Parallel pipelining

    SciTech Connect

    Joseph, D.D.; Bai, R.; Liao, T.Y.; Huang, A.; Hu, H.H.

    1995-09-01

    In this paper the authors introduce the idea of parallel pipelining for water lubricated transportation of oil (or other viscous material). A parallel system can have major advantages over a single pipe with respect to the cost of maintenance and continuous operation of the system, to the pressure gradients required to restart a stopped system and to the reduction and even elimination of the fouling of pipe walls in continuous operation. The authors show that the action of capillarity in small pipes is more favorable for restart than in large pipes. In a parallel pipeline system, they estimate the number of small pipes needed to deliver the same oil flux as in one larger pipe as N = (R/r){sup {alpha}}, where r and R are the radii of the small and large pipes, respectively, and {alpha} = 4 or 19/7 when the lubricating water flow is laminar or turbulent.

  11. Kin Recognition in a Clonal Fish, Poecilia formosa

    PubMed Central

    Makowicz, Amber M.; Tiedemann, Ralph; Schlupp, Ingo

    2016-01-01

    Relatedness strongly influences social behaviors in a wide variety of species. For most species, the highest typical degree of relatedness is between full siblings with 50% shared genes. However, this is poorly understood in species with unusually high relatedness between individuals: clonal organisms. Although there has been some investigation into clonal invertebrates and yeast, nothing is known about kin selection in clonal vertebrates. We show that a clonal fish, the Amazon molly (Poecilia formosa), can distinguish between different clonal lineages, associating with genetically identical, sister clones, and use multiple sensory modalities. Also, they scale their aggressive behaviors according to the relatedness to other females: they are more aggressive to non-related clones. Our results demonstrate that even in species with very small genetic differences between individuals, kin recognition can be adaptive. Their discriminatory abilities and regulation of costly behaviors provides a powerful example of natural selection in species with limited genetic diversity. PMID:27483372

  12. Antioxidant activities from different rosemary clonal lines.

    PubMed

    Ban, Lan; Narasimhamoorthy, Brindha; Zhao, Liuqing; Greaves, John A; Schroeder, William D

    2016-06-15

    Rosemary extract is widely used in food industry and carnosic acid is reported to be the major component that is responsible for its antioxidant activities. However, it is unclear how the numerous plant metabolites interact and contribute to the overall antioxidant activity. In this study, with poultry fat as the model food system, rosemary extract from six clonal lines were evaluated that each represented a different genetic variant. As expected, rosemary extract with higher carnosic acid content had higher antioxidant activity. However, rosemary extract which had carnosic acid removed retained a significant amount of activity. Furthermore, when the individual contributions of carnosic acid and the portion without carnosic acid were evaluated separately, neither was shown to be responsible for the overall level of its stabilization effect from rosemary extract as a whole entity. The interactions among different plant metabolites have a major impact on the overall antioxidant capabilities of rosemary extract.

  13. Clonal immunoglobulin gene rearrangement in the infarcted lymph node syndrome.

    PubMed

    Laszewski, M J; Belding, P J; Feddersen, R M; Lutz, C T; Goeken, J A; Kemp, J D; Dick, F R

    1991-07-01

    The authors report a case of complete lymph node infarction in which a specific etiology could not be determined by morphologic or immunophenotypic studies; however, clonal rearrangement of the immunoglobulin gene was demonstrated by Southern blot hybridization of DNA extracted from the necrotic tissue. A subsequent lymph node biopsy later was diagnosed as malignant lymphoma, using morphologic, immunophenotypic and genotypic criteria. Identical clonally rearranged bands were present in DNA from both the infarcted nodal and the subsequent tissue biopsies. In the setting of lymph node necrosis, gene rearrangement studies may provide diagnostic information concerning clonality, even if morphologic and immunophenotypic studies are indeterminate for a lymphoproliferative process.

  14. Effects of clonal integration on the invasive clonal plant Alternanthera philoxeroides under heterogeneous and homogeneous water availability

    PubMed Central

    You, Wen-Hua; Han, Cui-Min; Liu, Chun-Hua; Yu, Dan

    2016-01-01

    Many notorious invasive plants are clonal, living in heterogeneous or homogeneous habitats. To understand how clonal integration affects the performance of these plants in different habitat conditions, an 8-week greenhouse experiment was conducted: ramet pairs of A. philoxeroides were grown in two habitats, either heterogeneous or homogeneous in water availability, with the stolon connections either severed or kept intact. Under heterogeneous water availability, compared with ramets in homogeneous habitats, clonal integration significantly promoted the growth and photosynthetic performance of water-stressed apical ramets, whereas it only increased the photosynthetic performance but did not affect the growth of water-stressed basal ramets. Moreover, clonal integration markedly increased the root/shoot ratios of ramets grown in habitats with high water supply but decreased it under low water availability. Under homogeneous water availability, stolon connection (clonal integration) did not influence the growth, photosynthetic performance and biomass allocation of water-stressed ramets, but it significantly promoted the growth of well-watered ramets in both apical and basal sections. These findings deepen our understanding of the bidirectional and differentiated (mainly acropetal) clonal integration of A. philoxeroides, suggesting that the invasive plant A. philoxeroides can benefit from clonal integration in both heterogeneous and homogeneous habitats. PMID:27416868

  15. Molecular mimicry and clonal deletion: A fresh look.

    PubMed

    Rose, Noel R

    2015-06-21

    In this article, I trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. Clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. If we did have complete clonal deletion, there would be major voids, the infamous "black holes", in our immune repertoire. For comprehensive, protective adaptive immunity, full deletion is necessarily a rare event. Molecular mimicry, the sharing of epitopes among self and non-self antigens, is extraordinary common and provides the evidence that complete deletion of self-reactive clones is rare. If molecular mimicry were not common, protective adaptive immunity could not be all-encompassing. By taking a fresh look at these two processes together we can envision their evolutionary basis and understand the need for regulatory devices to prevent molecular mimicry from progressing to autoimmune disease.

  16. Clonal integration in Ludwigia hexapetala under different light regimes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physiological integration among ramets of invasive plant species may support their colonization and spread in novel aquatic environments where growth-limiting resources are spatially heterogeneous. Under contrasting light conditions, we investigated how clonal integration influences growth, biomass...

  17. Clonal Expansion (CE) Models in Cancer Risk Assessment

    EPA Science Inventory

    Cancer arises when cells accumulate sufficient critical mutations. Carcinogens increase the probability of mutation during cell division or promote clonal expansion within stages. Multistage CE models recapitulate this process and provide a framework for incorporating relevant da...

  18. Divergent clonal selection dominates medulloblastoma at recurrence

    PubMed Central

    Morrissy, A. Sorana; Garzia, Livia; Shih, David J. H.; Zuyderduyn, Scott; Huang, Xi; Skowron, Patryk; Remke, Marc; Cavalli, Florence M. G.; Ramaswamy, Vijay; Lindsay, Patricia E.; Jelveh, Salomeh; Donovan, Laura K.; Wang, Xin; Luu, Betty; Zayne, Kory; Li, Yisu; Mayoh, Chelsea; Thiessen, Nina; Mercier, Eloi; Mungall, Karen L.; Ma, Yusanne; Tse, Kane; Zeng, Thomas; Shumansky, Karey; Roth, Andrew J. L.; Shah, Sohrab; Farooq, Hamza; Kijima, Noriyuki; Holgado, Borja L.; Lee, John J. Y.; Matan-Lithwick, Stuart; Liu, Jessica; Mack, Stephen C.; Manno, Alex; Michealraj, K. A.; Nor, Carolina; Peacock, John; Qin, Lei; Reimand, Juri; Rolider, Adi; Thompson, Yuan Y.; Wu, Xiaochong; Pugh, Trevor; Ally, Adrian; Bilenky, Mikhail; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Young; Chuah, Eric; Corbett, Richard D.; Dhalla, Noreen; He, An; Lee, Darlene; Li, Haiyan I.; Long, William; Mayo, Michael; Plettner, Patrick; Qian, Jenny Q.; Schein, Jacqueline E.; Tam, Angela; Wong, Tina; Birol, Inanc; Zhao, Yongjun; Faria, Claudia C.; Pimentel, José; Nunes, Sofia; Shalaby, Tarek; Grotzer, Michael; Pollack, Ian F.; Hamilton, Ronald L.; Li, Xiao-Nan; Bendel, Anne E.; Fults, Daniel W.; Walter, Andrew W.; Kumabe, Toshihiro; Tominaga, Teiji; Collins, V. Peter; Cho, Yoon-Jae; Hoffman, Caitlin; Lyden, David; Wisoff, Jeffrey H.; Garvin, James H.; Stearns, Duncan S.; Massimi, Luca; Schüller, Ulrich; Sterba, Jaroslav; Zitterbart, Karel; Puget, Stephanie; Ayrault, Olivier; Dunn, Sandra E.; Tirapelli, Daniela P. C.; Carlotti, Carlos G.; Wheeler, Helen; Hallahan, Andrew R.; Ingram, Wendy; MacDonald, Tobey J.; Olson, Jeffrey J.; Van Meir, Erwin G.; Lee, Ji-Yeoun; Wang, Kyu-Chang; Kim, Seung-Ki; Cho, Byung-Kyu; Pietsch, Torsten; Fleischhack, Gudrun; Tippelt, Stephan; Ra, Young Shin; Bailey, Simon; Lindsey, Janet C.; Clifford, Steven C.; Eberhart, Charles G.; Cooper, Michael K.; Packer, Roger J.; Massimino, Maura; Garre, Maria Luisa; Bartels, Ute; Tabori, Uri; Hawkins, Cynthia E.; Dirks, Peter; Bouffet, Eric; Rutka, James T.; Wechsler-Reya, Robert J.; Weiss, William A.; Collier, Lara S.; Dupuy, Adam J.; Korshunov, Andrey; Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.; Largaespada, David A.; Mungall, Andrew J.; Moore, Richard A.; Jabado, Nada; Bader, Gary D.; Jones, Steven J. M.; Malkin, David; Marra, Marco A.; Taylor, Michael D.

    2016-01-01

    The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon–driven, functional genomic mouse model of medulloblastoma with ‘humanized’ in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy. PMID:26760213

  19. Roles of Clonal Integration in both Heterogeneous and Homogeneous Habitats

    PubMed Central

    Zhang, Haijie; Liu, Fenghong; Wang, Renqing; Liu, Jian

    2016-01-01

    Many studies have shown that clonal integration can promote the performance of clonal plants in heterogeneous habitats, but the roles of clonal integration in both heterogeneous and homogeneous habitats were rarely studied simultaneously. Ramet pairs of Alternanthera philoxeroides (Mart.) Griseb were placed in two habitats either heterogeneous or homogeneous in soil nutrient availability, with stolon connections left intact or severed. Total biomass, total length of stolons, and number of new ramets of distal (relatively young) ramets located in low-nutrient environments were significantly greater when the distal ramets were connected to than when they were disconnected from proximal (relatively old) ramets located in high-nutrient environments. Total length of stolons of proximal ramets growing in low-nutrient environments was significantly higher when the proximal ramets were connected to than when they were disconnected from the distal ramets growing in high-nutrient environments, but stolon connection did not affect total biomass or number of new ramets of the proximal ramets. Stolon severing also did not affect the growth of the whole ramet pairs in heterogeneous environments. In homogeneous high-nutrient environments stolon severing promoted the growth of the proximal ramets and the ramet pairs, but in homogeneous low-nutrient environments it did not affect the growth of the proximal or distal ramets. Hence, for A. philoxeroides, clonal fragmentation appears to be more advantageous than clonal integration in resource-rich homogeneous habitats, and clonal integration becomes beneficial in heterogeneous habitats. Our study contributes to revealing roles of clonal integration in both heterogeneous and homogeneous habitats and expansion patterns of invasive clonal plants such as A. philoxeroides in multifarious habitats. PMID:27200026

  20. Clonal structure and genetic diversity of three desert phreatophytes.

    PubMed

    Vonlanthen, Beatrix; Zhang, Ximing; Bruelheide, Helge

    2010-02-01

    The objective of this paper was to assess clone sizes of three perennial desert plant species with AFLP markers and to relate them to clonal and genetic diversity and to hydroecology. The study was carried out at the southern rim of the Taklamakan Desert, where sexual regeneration is only possible shortly after rare flooding events, resulting in rarely established cohorts with subsequent extensive vertical growth and horizontal clonal spread. In this environment, repeated seedling establishment is excluded. We expected decreasing clonal and genetic diversity with increasing clone size and increasing distance to the groundwater table and a common response pattern among all study species. Maximum sizes of Populus euphratica and Alhagi sparsifolia clones were 121 ha and 6.1 ha, respectively, while Tamarix ramosissima clones reached a maximum size of only 38 m(2). In P. euphratica and A. sparsifolia, clonal diversity declined with increasing clone size and increasing distance to the groundwater table, while genetic diversity remained unaffected. Tamarix ramosissima differed from the other species because of a much smaller clonality. Clone size and clonal diversity were found to be good proxy variables for clone age. Despite the considerable age of the clones, genetic diversity is maintained in the populations.

  1. Pityriasis lichenoides: a clonal T-cell lymphoproliferative disorder.

    PubMed

    Magro, Cynthia; Crowson, A Neil; Kovatich, Al; Burns, Frank

    2002-08-01

    the epidermis. In 17 biopsies in which a CD4 stain was satisfactory for evaluation, 50% or more of the intraepidermal population was CD4 positive in 8 biopsies, whereas in 11 biopsies 50% or more of the dermal infiltrate was CD4 positive. The CD4-positive cells frequently had a cerebriform nuclear morphology and were CD7 negative. Most cases had an admixture of CD8-positive lymphocytes in excess of 40% or more of the intraepidermal and/or dermal infiltrate; it was the dominant intraepidermal infiltrate in 10 cases. The CD8-positive cells, typically small, round, and CD7 positive, showed a directed pattern of migration into acrosyringia and suprapapillary plates, with satellitosis around CD4-positive/CD8-negative/CD7-negative atypical lymphocytes. CD56 positivity was seen among the intraepidermal lymphoid cells and roughly paralleled the CD8 profile. In general, CD8-positive lymphocytes dominated in cases of PLEVA, whereas CD4-positive lymphocytes were very conspicuous and composed the dominant intraepidermal populace only in those biopsies of progressive PL/PLC. Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained. Intraepithelial atypical lymphocytes, phenotypic abnormalities, and TCR-gamma rearrangements suggest that PLC and PLEVA are a form of T-cell dyscrasia. Lesions may follow a recalcitrant course characteristic of MF and premycotic disorders such as LPP. The aberrant phenotype cell is similar to that defining MF: a CD4-positive T lymphocyte with a CD5 and CD7 deletion. Directed epidermal migration seen in biopsies procured from incipient lesions along with occasional temporal association to viral or drug exposure suggests that an abnormal immune response to an antigenic trigger may be the inciting event.

  2. An Invasive Clonal Plant Benefits from Clonal Integration More than a Co-Occurring Native Plant in Nutrient-Patchy and Competitive Environments

    PubMed Central

    You, Wenhua; Fan, Shufeng; Yu, Dan; Xie, Dong; Liu, Chunhua

    2014-01-01

    Many notorious invasive plants are clonal, however, little is known about the different roles of clonal integration effects between invasive and native plants. Here, we hypothesize that clonal integration affect growth, photosynthetic performance, biomass allocation and thus competitive ability of invasive and native clonal plants, and invasive clonal plants benefit from clonal integration more than co-occurring native plants in heterogeneous habitats. To test these hypotheses, two stoloniferous clonal plants, Alternanthera philoxeroides (invasive), Jussiaea repens (native) were studied in China. The apical parts of both species were grown either with or without neighboring vegetation and the basal parts without competitors were in nutrient- rich or -poor habitats, with stolon connections were either severed or kept intact. Competition significantly reduced growth and photosynthetic performance of the apical ramets in both species, but not the biomass of neighboring vegetation. Without competition, clonal integration greatly improved the growth and photosynthetic performance of both species, especially when the basal parts were in nutrient-rich habitats. When grown with neighboring vegetation, growth of J. repens and photosynthetic performance of both species were significantly enhanced by clonal integration with the basal parts in both nutrient-rich and -poor habitats, while growth and relative neighbor effect (RNE) of A. philoxeroides were greatly improved by clonal integration only when the basal parts were in nutrient-rich habitats. Moreover, clonal integration increased A. philoxeroides's biomass allocation to roots without competition, but decreased it with competition, especially when the basal ramets were in nutrient-rich sections. Effects of clonal integration on biomass allocation of J. repens was similar to that of A. philoxeroides but with less significance. These results supported our hypothesis that invasive clonal plants A. philoxeroides benefits

  3. An invasive clonal plant benefits from clonal integration more than a co-occurring native plant in nutrient-patchy and competitive environments.

    PubMed

    You, Wenhua; Fan, Shufeng; Yu, Dan; Xie, Dong; Liu, Chunhua

    2014-01-01

    Many notorious invasive plants are clonal, however, little is known about the different roles of clonal integration effects between invasive and native plants. Here, we hypothesize that clonal integration affect growth, photosynthetic performance, biomass allocation and thus competitive ability of invasive and native clonal plants, and invasive clonal plants benefit from clonal integration more than co-occurring native plants in heterogeneous habitats. To test these hypotheses, two stoloniferous clonal plants, Alternanthera philoxeroides (invasive), Jussiaea repens (native) were studied in China. The apical parts of both species were grown either with or without neighboring vegetation and the basal parts without competitors were in nutrient- rich or -poor habitats, with stolon connections were either severed or kept intact. Competition significantly reduced growth and photosynthetic performance of the apical ramets in both species, but not the biomass of neighboring vegetation. Without competition, clonal integration greatly improved the growth and photosynthetic performance of both species, especially when the basal parts were in nutrient-rich habitats. When grown with neighboring vegetation, growth of J. repens and photosynthetic performance of both species were significantly enhanced by clonal integration with the basal parts in both nutrient-rich and -poor habitats, while growth and relative neighbor effect (RNE) of A. philoxeroides were greatly improved by clonal integration only when the basal parts were in nutrient-rich habitats. Moreover, clonal integration increased A. philoxeroides's biomass allocation to roots without competition, but decreased it with competition, especially when the basal ramets were in nutrient-rich sections. Effects of clonal integration on biomass allocation of J. repens was similar to that of A. philoxeroides but with less significance. These results supported our hypothesis that invasive clonal plants A. philoxeroides benefits

  4. Propagule Pressure, Habitat Conditions and Clonal Integration Influence the Establishment and Growth of an Invasive Clonal Plant, Alternanthera philoxeroides.

    PubMed

    You, Wen-Hua; Han, Cui-Min; Fang, Long-Xiang; Du, Dao-Lin

    2016-01-01

    Many notorious invasive plants are clonal, spreading mainly by vegetative propagules. Propagule pressure (the number of propagules) may affect the establishment, growth, and thus invasion success of these clonal plants, and such effects may also depend on habitat conditions. To understand how propagule pressure, habitat conditions and clonal integration affect the establishment and growth of the invasive clonal plants, an 8-week greenhouse with an invasive clonal plant, Alternanthera philoxeroides was conducted. High (five fragments) or low (one fragment) propagule pressure was established either in bare soil (open habitat) or dense native vegetation of Jussiaea repens (vegetative habitat), with the stolon connections either severed from or connected to the relatively older ramets. High propagule pressure greatly increased the establishment and growth of A. philoxeroides, especially when it grew in vegetative habitats. Surprisingly, high propagule pressure significantly reduced the growth of individual plants of A. philoxeroides in open habitats, whereas it did not affect the individual growth in vegetative habitats. A shift in the intraspecific interaction on A. philoxeroides from competition in open habitats to facilitation in vegetative habitats may be the main reason. Moreover, clonal integration significantly improved the growth of A. philoxeroides only in open habitats, especially with low propagule pressure, whereas it had no effects on the growth and competitive ability of A. philoxeroides in vegetative habitats, suggesting that clonal integration may be of most important for A. philoxeroides to explore new open space and spread. These findings suggest that propagule pressure may be crucial for the invasion success of A. philoxeroides, and such an effect also depends on habitat conditions.

  5. Propagule Pressure, Habitat Conditions and Clonal Integration Influence the Establishment and Growth of an Invasive Clonal Plant, Alternanthera philoxeroides

    PubMed Central

    You, Wen-Hua; Han, Cui-Min; Fang, Long-Xiang; Du, Dao-Lin

    2016-01-01

    Many notorious invasive plants are clonal, spreading mainly by vegetative propagules. Propagule pressure (the number of propagules) may affect the establishment, growth, and thus invasion success of these clonal plants, and such effects may also depend on habitat conditions. To understand how propagule pressure, habitat conditions and clonal integration affect the establishment and growth of the invasive clonal plants, an 8-week greenhouse with an invasive clonal plant, Alternanthera philoxeroides was conducted. High (five fragments) or low (one fragment) propagule pressure was established either in bare soil (open habitat) or dense native vegetation of Jussiaea repens (vegetative habitat), with the stolon connections either severed from or connected to the relatively older ramets. High propagule pressure greatly increased the establishment and growth of A. philoxeroides, especially when it grew in vegetative habitats. Surprisingly, high propagule pressure significantly reduced the growth of individual plants of A. philoxeroides in open habitats, whereas it did not affect the individual growth in vegetative habitats. A shift in the intraspecific interaction on A. philoxeroides from competition in open habitats to facilitation in vegetative habitats may be the main reason. Moreover, clonal integration significantly improved the growth of A. philoxeroides only in open habitats, especially with low propagule pressure, whereas it had no effects on the growth and competitive ability of A. philoxeroides in vegetative habitats, suggesting that clonal integration may be of most important for A. philoxeroides to explore new open space and spread. These findings suggest that propagule pressure may be crucial for the invasion success of A. philoxeroides, and such an effect also depends on habitat conditions. PMID:27200041

  6. Molecular epidemiology of clonal diploids: a quick overview and a short DIY (do it yourself) notice.

    PubMed

    De Meeûs, Thierry; Lehmann, Laurent; Balloux, François

    2006-03-01

    In this short review we report the basic notions needed for understanding the population genetics of clonal diploids. We focus on the consequences of clonality on the distribution of genetic diversity within individuals, between individuals and between populations. We then summarise how to detect clonality in mainly sexual populations, conversely, how to detect sexuality in mainly clonal populations and also how genetic differentiation between populations is affected by clonality in diploids. This information is then used for building recipes on how to analyse and interpret genetic polymorphism data in molecular epidemiology studies of clonal diploids.

  7. Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia

    PubMed Central

    Yeh, Paul; Hunter, Tane; Sinha, Devbarna; Ftouni, Sarah; Wallach, Elise; Jiang, Damian; Chan, Yih-Chih; Wong, Stephen Q.; Silva, Maria Joao; Vedururu, Ravikiran; Doig, Kenneth; Lam, Enid; Arnau, Gisela Mir; Semple, Timothy; Wall, Meaghan; Zivanovic, Andjelija; Agarwal, Rishu; Petrone, Pasquale; Jones, Kate; Westerman, David; Blombery, Piers; Seymour, John F.; Papenfuss, Anthony T.; Dawson, Mark A.; Tam, Constantine S.; Dawson, Sarah-Jane

    2017-01-01

    Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter's syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring. PMID:28303898

  8. Reproductive clonality in protozoan pathogens--truth or artefact?

    PubMed

    Ramírez, Juan David; Llewellyn, Martin S

    2014-09-01

    The debate around the frequency and importance of genetic exchange in parasitic protozoa is now several decades old. Recently, fresh assertions have been made that predominant clonal evolution explains the population structures of several key protozoan pathogens. Here, we present an alternative perspective. On the assumption that much apparent clonality may be an artefact of inadequate sampling and study design, we review current research to define why sex might be so difficult to detect in protozoan parasite populations. In doing so, we contrast laboratory models of genetic exchange in parasitic protozoa with natural patterns of genetic diversity and consider the fitness advantage of sex at different evolutionary scales. We discuss approaches to improve the accuracy of efforts to characterize genetic exchange in the field. We also examine the implications of the first population genomic studies for the debate around sex and clonality in parasitic protozoa and discuss caveats for the future.

  9. Establishment of functional clonal lines of neurons from mouse neuroblastoma.

    PubMed

    Augusti-Tocco, G; Sato, G

    1969-09-01

    Clonal lines of neurons were obtained in culture from a mouse neuroblastoma. The neuroblastoma cells were adapted to culture growth by the animal-culture alternate passage technique and cloned after single-cell plating. The clonal lines retained the ability to form tumors when injected back into mice. A striking morphological change was observed in the cells adapted to culture growth; they appeared as mature neurons, while the cells of the tumor appeared as immature neuroblasts. Acetylcholinesterase and the enzymes for the synthesis of neurotransmitters, cholineacetylase and tyrosine hydroxylase were assayed in the tumor and compared with brain levels; tyrosine hydroxylase was found to be particularly high, as described previously in human neuroblastomas. The three enzymes were found in the clonal cultures at levels comparable to those found in the tumors. Similarly, there were no remarkable differences between the three clones examined.

  10. Is Having Clonal Cytogenetic Abnormalities the Same as Having Leukaemia.

    PubMed

    Farina, Mirko; Rossi, Giuseppe; Bellotti, Daniella; Marchina, Eleonora; Gale, Robert Peter

    2016-01-01

    A finding of cytogenetic abnormalities, even when these are clonal and even when the abnormalities are typically associated with leukaemia, is not the same as a person having leukaemia. We describe a person who had acute myeloid leukaemia (AML) and achieved a complete haematological remission and who then had persistent and transient clonal cytogenetic abnormalities for 22 years but no recurrence of leukaemia. These data suggest that clones of myeloid cells with mutations and capable of expanding to levels detectable by routine cytogenetic analyses do not all eventuate in leukaemia, even after a prolonged observation interval. The possibility of incorrectly diagnosing a person as having leukaemia becomes even greater when employing more sensitive techniques to detect mutations such as by polymerase chain reaction and whole-exome or whole-genome sequencing. Caution is needed when interpreting clonal abnormalities in AML patients with normal blood and bone marrow parameters.

  11. Enumeration of Neural Stem Cells Using Clonal Assays

    PubMed Central

    Narayanan, Gunaseelan; Yu, Yuan Hong; Tham, Muly; Gan, Hui Theng; Ramasamy, Srinivas; Sankaran, Shvetha; Hariharan, Srivats; Ahmed, Sohail

    2016-01-01

    Neural stem cells (NSCs) have the ability to self-renew and generate the three major neural lineages — astrocytes, neurons and oligodendrocytes. NSCs and neural progenitors (NPs) are commonly cultured in vitro as neurospheres. This protocol describes in detail how to determine the NSC frequency in a given cell population under clonal conditions. The protocol begins with the seeding of the cells at a density that allows for the generation of clonal neurospheres. The neurospheres are then transferred to chambered coverslips and differentiated under clonal conditions in conditioned medium, which maximizes the differentiation potential of the neurospheres. Finally, the NSC frequency is calculated based on neurosphere formation and multipotency capabilities. Utilities of this protocol include the evaluation of candidate NSC markers, purification of NSCs, and the ability to distinguish NSCs from NPs. This method takes 13 days to perform, which is much shorter than current methods to enumerate NSC frequency. PMID:27768074

  12. Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus

    PubMed Central

    Martinez, Pierre; Timmer, Margriet R.; Lau, Chiu T.; Calpe, Silvia; Sancho-Serra, Maria del Carmen; Straub, Danielle; Baker, Ann-Marie; Meijer, Sybren L.; Kate, Fiebo J. W. ten; Mallant-Hent, Rosalie C.; Naber, Anton H. J.; van Oijen, Arnoud H. A. M.; Baak, Lubbertus C.; Scholten, Pieter; Böhmer, Clarisse J. M.; Fockens, Paul; Bergman, Jacques J. G. H. M.; Maley, Carlo C.; Graham, Trevor A.; Krishnadath, Kausilia K

    2016-01-01

    Surveillance of Barrett's oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm2 (95% CI: 0.09–4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett's and that the malignant potential of ‘benign' Barrett's lesions is predetermined, with important implications for surveillance programs. PMID:27538785

  13. An Expanded Lateral Interactive Clonal Selection Algorithm and Its Application

    NASA Astrophysics Data System (ADS)

    Gao, Shangce; Dai, Hongwei; Zhang, Jianchen; Tang, Zheng

    Based on the clonal selection principle proposed by Burnet, in the immune response process there is no crossover of genetic material between members of the repertoire, i. e., there is no knowledge communication during different elite pools in the previous clonal selection models. As a result, the search performance of these models is ineffective. To solve this problem, inspired by the concept of the idiotypic network theory, an expanded lateral interactive clonal selection algorithm (LICS) is put forward. In LICS, an antibody is matured not only through the somatic hypermutation and the receptor editing from the B cell, but also through the stimuli from other antibodies. The stimuli is realized by memorizing some common gene segment on the idiotypes, based on which a lateral interactive receptor editing operator is also introduced. Then, LICS is applied to several benchmark instances of the traveling salesman problem. Simulation results show the efficiency and robustness of LICS when compared to other traditional algorithms.

  14. Parallel pivoting combined with parallel reduction

    NASA Technical Reports Server (NTRS)

    Alaghband, Gita

    1987-01-01

    Parallel algorithms for triangularization of large, sparse, and unsymmetric matrices are presented. The method combines the parallel reduction with a new parallel pivoting technique, control over generations of fill-ins and a check for numerical stability, all done in parallel with the work being distributed over the active processes. The parallel technique uses the compatibility relation between pivots to identify parallel pivot candidates and uses the Markowitz number of pivots to minimize fill-in. This technique is not a preordering of the sparse matrix and is applied dynamically as the decomposition proceeds.

  15. [Clonality lymphoid study through rearrangement analysis of antigen receptor].

    PubMed

    Villamizar-Rivera, Nicolás; Olaya, Natalia

    2015-01-01

    As a rule, malignant lymphoid proliferations are clonal. While most of the time the biological potential can be established through routine pathologic examination and auxiliary techniques, some cases are difficult to classify. Moreover, there are situations in which there are dominant clones whose analysis are important, such as occur in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality in lymphoid lesions, i.e. the analysis of rearrangements of antigen receptor genes by multiplex polymerase chain reaction (PCR) based tests.

  16. Is pure red cell aplasia (PRCA) a clonal disorder?

    PubMed

    Sivakumaran, M; Bhavnani, M; Stewart, A; Roberts, B E; Geary, G C

    1993-01-01

    Pure red cell aplasia (PRCA) is an uncommon disorder, many cases lacking a well defined aetiology. This report describes three cases of PRCA (two idiopathic and one associated with B-CLL) who were investigated to assess the possibility of their PRCA being associated with a clonal proliferation of T-lymphocytes. The results show that one patient had evidence of T-cell receptor (TCR) gamma chain rearrangement, and the other had a TCR delta chain rearrangement. These two cases raise the possibility of PRCA being associated with a clonal proliferation of T-cells and further studies are warranted.

  17. Generation of clonal zebrafish line by androgenesis without egg irradiation

    PubMed Central

    Hou, Jilun; Fujimoto, Takafumi; Saito, Taiju; Yamaha, Etsuro; Arai, Katsutoshi

    2015-01-01

    Generation of clonal zebrafish will facilitate large-scale genetic screening and help us to overcome other biological and biotechnological challenges due to their isogenecity. However, protocols for the development of clonal lines have not been optimized. Here, we sought to develop a novel method for generation of clonal zebrafish by androgenesis induced by cold shock. Androgenetic zebrafish doubled haploids (DHs) were induced by cold shock of just-fertilized eggs, and the eggs were then heat shocked to double the chromosome set. The yield rate of putative DHs relative to the total number of eggs used was 1.10% ± 0.19%. Microsatellite genotyping of the putative DHs using 30 loci that covered all 25 linkage groups detected no heterozygous loci, confirming the homozygosity of the DHs. Thus, a clonal line was established from sperm of a DH through a second cycle of cold-shock androgenesis and heat-shock chromosome doubling, followed by genetic verification of the isogenic rate confirming the presence of identical DNA fingerprints by using amplified fragment length polymorphism markers. In addition, our data provided important insights into the cytological mechanisms of cold-shock–induced androgenesis. PMID:26289165

  18. Clonal Outbreak of Plasmodium falciparum Infection in Eastern Panama

    PubMed Central

    Obaldia, Nicanor; Baro, Nicholas K.; Calzada, Jose E.; Santamaria, Ana M.; Daniels, Rachel; Wong, Wesley; Chang, Hsiao-Han; Hamilton, Elizabeth J.; Arevalo-Herrera, Myriam; Herrera, Socrates; Wirth, Dyann F.; Hartl, Daniel L.; Marti, Matthias; Volkman, Sarah K.

    2015-01-01

    Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although the malaria incidence in Panama is low, a recent outbreak resulted in a 6-fold increase in reported cases. We hypothesized that parasites sampled from this epidemic might be related and exhibit a clonal population structure. We tested the genetic relatedness of parasites, using informative single-nucleotide polymorphisms and drug resistance loci. We found that parasites were clustered into 3 clonal subpopulations and were related to parasites from Colombia. Two clusters of Panamanian parasites shared identical drug resistance haplotypes, and all clusters shared a chloroquine-resistance genotype matching the pfcrt haplotype of Colombian origin. Our findings suggest these resurgent parasite populations are highly clonal and that the high clonality likely resulted from epidemic expansion of imported or vestigial cases. Malaria outbreak investigations that use genetic tools can illuminate potential sources of epidemic malaria and guide strategies to prevent further resurgence in areas where malaria has been eliminated. PMID:25336725

  19. Phenotypic differences among three clonal lineages of Phytophthora ramorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are three major clonal lineages of Phytophthora ramorum present in North America and Europe named NA1, NA2, and EU1. Twenty-three isolates representing all three lineages were evaluated for phenotype including (i) aggressiveness on detached Rhododendron leaves and (ii) growth rate at minimum, ...

  20. Special parallel processing workshop

    SciTech Connect

    1994-12-01

    This report contains viewgraphs from the Special Parallel Processing Workshop. These viewgraphs deal with topics such as parallel processing performance, message passing, queue structure, and other basic concept detailing with parallel processing.

  1. Stem cell clonality -- theoretical concepts, experimental techniques, and clinical challenges.

    PubMed

    Glauche, Ingmar; Bystrykh, Leonid; Eaves, Connie; Roeder, Ingo

    2013-04-01

    Here we report highlights of discussions and results presented at an International Workshop on Concepts and Models of Stem Cell Organization held on July 16th and 17th, 2012 in Dresden, Germany. The goal of the workshop was to undertake a systematic survey of state-of-the-art methods and results of clonality studies of tissue regeneration and maintenance with a particular emphasis on the hematopoietic system. The meeting was the 6th in a series of similar conceptual workshops, termed StemCellMathLab,(2) all of which have had the general objective of using an interdisciplinary approach to discuss specific aspects of stem cell biology. The StemCellMathLab 2012, which was jointly organized by the Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Dresden University of Technology and the Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, brought together 32 scientists from 8 countries, with scientific backgrounds in medicine, cell biology, virology, physics, computer sciences, bioinformatics and mathematics. The workshop focused on the following questions: (1) How heterogeneous are stem cells and their progeny? and (2) What are the characteristic differences in the clonal dynamics between physiological and pathophysiological situations? In discussing these questions, particular emphasis was placed on (a) the methods for quantifying clones and their dynamics in experimental and clinical settings and (b) general concepts and models for their description. In this workshop summary we start with an introduction to the current state of clonality research and a proposal for clearly defined terminology. Major topics of discussion include clonal heterogeneity in unperturbed tissues, clonal dynamics due to physiological and pathophysiological pressures and conceptual and technical issues of clone quantification. We conclude that an interactive cross-disciplinary approach to research in this

  2. Parallel rendering techniques for massively parallel visualization

    SciTech Connect

    Hansen, C.; Krogh, M.; Painter, J.

    1995-07-01

    As the resolution of simulation models increases, scientific visualization algorithms which take advantage of the large memory. and parallelism of Massively Parallel Processors (MPPs) are becoming increasingly important. For large applications rendering on the MPP tends to be preferable to rendering on a graphics workstation due to the MPP`s abundant resources: memory, disk, and numerous processors. The challenge becomes developing algorithms that can exploit these resources while minimizing overhead, typically communication costs. This paper will describe recent efforts in parallel rendering for polygonal primitives as well as parallel volumetric techniques. This paper presents rendering algorithms, developed for massively parallel processors (MPPs), for polygonal, spheres, and volumetric data. The polygon algorithm uses a data parallel approach whereas the sphere and volume render use a MIMD approach. Implementations for these algorithms are presented for the Thinking Ma.chines Corporation CM-5 MPP.

  3. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

    PubMed

    Kuraoka, Masayuki; Schmidt, Aaron G; Nojima, Takuya; Feng, Feng; Watanabe, Akiko; Kitamura, Daisuke; Harrison, Stephen C; Kepler, Thomas B; Kelsoe, Garnett

    2016-03-15

    Germinal center (GC) B cells evolve toward increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two complex antigens-Bacillus anthracis protective antigen and influenza hemagglutinin-in which B cells competed both intra- and interclonally for distinct epitopes. Preferred VH rearrangements among antigen-binding, naive B cells were similarly abundant in early GCs but, unlike responses to haptens, clonal diversity increased in GC B cells as early "winners" were replaced by rarer, high-affinity clones. Despite affinity maturation, inter- and intraclonal avidities varied greatly, and half of GC B cells did not bind the immunogen but nonetheless exhibited biased VH use, V(D)J mutation, and clonal expansion comparable to antigen-binding cells. GC reactions to complex antigens permit a range of specificities and affinities, with potential advantages for broad protection.

  4. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  5. Defining the clonal dynamics leading to mouse skin tumour initiation

    PubMed Central

    Sánchez-Danés, Adriana; Hannezo, Edouard; Larsimont, Jean-Christophe; Liagre, Mélanie; Youssef, Khalil Kass; Simons, Benjamin D; Blanpain, Cédric

    2016-01-01

    The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase of symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is not only dependent on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin. PMID:27459053

  6. Clonal forestry, heterosis and advanced-generation breeding

    SciTech Connect

    Tuskan, G.A.

    1997-08-01

    This report discusses the clonal planting stock offers many advantages to the forest products industry. Advanced-generation breeding strategies should be designed to maximize within-family variance and at the same time allow the capture of heterosis. Certainly there may be a conflict in the choice of breeding strategy based on the trait of interest. It may be that the majority of the traits express heterosis due to overdominance. Alternatively, disease resistance is expressed as the lack of a specific metabolite or infection court then the homozygous recessive genotype may be the most desirable. Nonetheless, as the forest products industry begins to utilize the economic advantages of clonal forestry, breeding strategies will have to be optimized for these commercial plant materials. Here, molecular markers can be used to characterize the nature of heterosis and therefore define the appropriate breeding strategy.

  7. Clonal propagation of chemically uniform fennel plants through somatic embryoids.

    PubMed

    Miura, Y; Fukui, H; Tabata, M

    1987-02-01

    Somatic embryoids obtained from cell suspension cultures of fennel in Linsmaier-Skoog medium containing 2,4-D and kinetin readily developed into plantlets when plated on a hormone-free agar medium. These plants were transplanted to the field to be tested for the uniformity of the chemically as well as the morphologically important characteristics of fruits. The results of field trials conducted for two years have confirmed that the clonal plants derived from somatic embryoids are remarkably uniform in all the characteristics examined in comparison with the control plants propagated through seeds. It is suggested, therefore, that the quality control of fennel fruits used for spice or medicine could be achieved by means of clonal propagation through somatic embryoids.

  8. Wide Dispersion and Diversity of Clonally Related Inhibitory Interneurons.

    PubMed

    Harwell, Corey C; Fuentealba, Luis C; Gonzalez-Cerrillo, Adrian; Parker, Phillip R L; Gertz, Caitlyn C; Mazzola, Emanuele; Garcia, Miguel Turrero; Alvarez-Buylla, Arturo; Cepko, Constance L; Kriegstein, Arnold R

    2015-09-02

    The mammalian neocortex is composed of two major neuronal cell types with distinct origins: excitatory pyramidal neurons and inhibitory interneurons, generated in dorsal and ventral progenitor zones of the embryonic telencephalon, respectively. Thus, inhibitory neurons migrate relatively long distances to reach their destination in the developing forebrain. The role of lineage in the organization and circuitry of interneurons is still not well understood. Utilizing a combination of genetics, retroviral fate mapping, and lineage-specific retroviral barcode labeling, we find that clonally related interneurons can be widely dispersed while unrelated interneurons can be closely clustered. These data suggest that migratory mechanisms related to the clustering of interneurons occur largely independent of their clonal origin.

  9. Clonal Analysis of the Microbiota of Severe Early Childhood Caries

    PubMed Central

    Kanasi, E.; Dewhirst, F.E.; Chalmers, N.I.; Kent, R.; Moore, A.; Hughes, C.V.; Pradhan, N.; Loo, C.Y.; Tanner, A.C.R.

    2010-01-01

    Background/Aims Severe early childhood caries is a microbial infection that severely compromises the dentition of young children. The aim of this study was to characterize the microbiota of severe early childhood caries. Methods Dental plaque samples from 2- to 6-year-old children were analyzed using 16S rRNA gene cloning and sequencing, and by specific PCR amplification for Streptococcus mutans and Bifidobacteriaceae species. Results Children with severe caries (n = 39) had more dental plaque and gingival inflammation than caries-free children (n = 41). Analysis of phylotypes from operational taxonomic unit analysis of 16S rRNA clonal metalibraries from severe caries and caries-free children indicated that while libraries differed significantly (p < 0.0001), there was increased diversity than detected in this clonal analysis. Using the Human Oral Microbiome Database, 139 different taxa were identified. Within the limits of this study, caries-associated taxa included Granulicatella elegans (p < 0.01) and Veillonella sp. HOT-780 (p < 0.01). The species associated with caries-free children included Capnocytophaga gingivalis (p < 0.01), Abiotrophia defectiva (p < 0.01), Lachnospiraceae sp. HOT-100 (p < 0.05), Streptococcus sanguinis (p < 0.05) and Streptococcus cristatus (p < 0.05). By specific PCR, S. mutans (p < 0.005) and Bifidobacteriaceae spp. (p < 0.0001) were significantly associated with severe caries. Conclusion Clonal analysis of 80 children identified a diverse microbiota that differed between severe caries and caries-free children, but the association of S. mutans with caries was from specific PCR analysis, not from clonal analysis, of samples. PMID:20861633

  10. Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia

    PubMed Central

    Lang, Fabian; Wojcik, Bartosch; Rieger, Michael A.

    2015-01-01

    Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients' outcome in ALL. PMID:26236346

  11. Likelihood-Based Inference of B Cell Clonal Families

    PubMed Central

    Ralph, Duncan K.

    2016-01-01

    The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called “rearrangement” forming progenitor B cells, then a Darwinian process of lineage diversification and selection called “affinity maturation.” The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member. As a step to understanding the process and result of this diversification, one may wish to reconstruct lineage membership, i.e. to cluster sampled sequences according to which came from the same rearrangement events. We call this clustering problem “clonal family inference.” In this paper we describe and validate a likelihood-based framework for clonal family inference based on a multi-hidden Markov Model (multi-HMM) framework for B cell receptor sequences. We describe an agglomerative algorithm to find a maximum likelihood clustering, two approximate algorithms with various trade-offs of speed versus accuracy, and a third, fast algorithm for finding specific lineages. We show that under simulation these algorithms greatly improve upon existing clonal family inference methods, and that they also give significantly different clusters than previous methods when applied to two real data sets. PMID:27749910

  12. Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity.

    PubMed

    Turpin, Jocelyn; Alais, Sandrine; Marçais, Ambroise; Bruneau, Julie; Melamed, Anat; Gadot, Nicolas; Tanaka, Yuetsu; Hermine, Olivier; Melot, Sandrine; Lacoste, Romain; Bangham, Charles R; Mahieux, Renaud

    2017-03-28

    HTLV-1 causes Adult T cell Leukemia/Lymphoma (ATLL) in humans. We describe an ATL-like disease in a 9 year-old female baboon naturally infected with STLV-1 (the simian counterpart of HTLV-1), with a lymphocyte count over 10(10)/L, lymphocytes with abnormal nuclear morphology, and pulmonary and skin lesions. The animal was treated with a combination of AZT and alpha interferon. Proviral load (PVL) was measured every week. Because the disease continued to progress, the animal was euthanized. Abnormal infiltrates of CD3(+)CD25(+) lymphocytes and Tax-positive cells were found by histological analyses in both lymphoid and non-lymphoid organs. PVL was measured and clonal diversity was assessed by LM-PCR (Ligation-Mediated Polymerase Chain Reaction) and high throughput sequencing, in blood during treatment and in 14 different organs. The highest PVL was found in lymph nodes, spleen and lungs. One major clone and a number of intermediate abundance clones were present in blood throughout the course of treatment, and in organs. These results represent the first multi-organ clonality study in ATLL. We demonstrate a previously undescribed clonal complexity in ATLL. Our data reinforce the usefulness of natural STLV-1 infection as a model of ATLL.

  13. Parallel flow diffusion battery

    DOEpatents

    Yeh, Hsu-Chi; Cheng, Yung-Sung

    1984-08-07

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  14. Parallel flow diffusion battery

    DOEpatents

    Yeh, H.C.; Cheng, Y.S.

    1984-01-01

    A parallel flow diffusion battery for determining the mass distribution of an aerosol has a plurality of diffusion cells mounted in parallel to an aerosol stream, each diffusion cell including a stack of mesh wire screens of different density.

  15. Parallel processing ITS

    SciTech Connect

    Fan, W.C.; Halbleib, J.A. Sr.

    1996-09-01

    This report provides a users` guide for parallel processing ITS on a UNIX workstation network, a shared-memory multiprocessor or a massively-parallel processor. The parallelized version of ITS is based on a master/slave model with message passing. Parallel issues such as random number generation, load balancing, and communication software are briefly discussed. Timing results for example problems are presented for demonstration purposes.

  16. Research in parallel computing

    NASA Technical Reports Server (NTRS)

    Ortega, James M.; Henderson, Charles

    1994-01-01

    This report summarizes work on parallel computations for NASA Grant NAG-1-1529 for the period 1 Jan. - 30 June 1994. Short summaries on highly parallel preconditioners, target-specific parallel reductions, and simulation of delta-cache protocols are provided.

  17. Parallel simulation today

    NASA Technical Reports Server (NTRS)

    Nicol, David; Fujimoto, Richard

    1992-01-01

    This paper surveys topics that presently define the state of the art in parallel simulation. Included in the tutorial are discussions on new protocols, mathematical performance analysis, time parallelism, hardware support for parallel simulation, load balancing algorithms, and dynamic memory management for optimistic synchronization.

  18. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity.

    PubMed

    Marusyk, Andriy; Tabassum, Doris P; Altrock, Philipp M; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia

    2014-10-02

    Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

  19. Clonal integration of Fragaria orientalis in reciprocal and coincident patchiness resources: cost-benefit analysis.

    PubMed

    Zhang, Yunchun; Zhang, Qiaoying

    2013-01-01

    Clonal growth allows plants to spread horizontally and to experience different levels of resources. If ramets remain physiologically integrated, clonal plants can reciprocally translocate resources between ramets in heterogeneous environments. But little is known about the interaction between benefits of clonal integration and patterns of resource heterogeneity in different patches, i.e., coincident patchiness or reciprocal patchiness. We hypothesized that clonal integration will show different effects on ramets in different patches and more benefit to ramets under reciprocal patchiness than to those under coincident patchiness, as well as that the benefit from clonal integration is affected by the position of proximal and distal ramets under reciprocal or coincident patchiness. A pot experiment was conducted with clonal fragments consisting of two interconnected ramets (proximal and distal ramet) of Fragaria orientalis. In the experiment, proximal and distal ramets were grown in high or low availability of resources, i.e., light and water. Resource limitation was applied either simultaneously to both ramets of a clonal fragment (coincident resource limitation) or separately to different ramets of the same clonal fragment (reciprocal resource limitation). Half of the clonal fragments were connected while the other half were severed. From the experiment, clonal fragments growing under coincident resource limitation accumulated more biomass than those under reciprocal resource limitation. Based on a cost-benefit analysis, the support from proximal ramets to distal ramets was stronger than that from distal ramets to proximal ramets. Through division of labour, clonal fragments of F. orientalis benefited more in reciprocal patchiness than in coincident patchiness. While considering biomass accumulation and ramets production, coincident patchiness were more favourable to clonal plant F. orientalis.

  20. Antigen-specific CD4{sup +} effector T cells: Analysis of factors regulating clonal expansion and cytokine production

    SciTech Connect

    Ohnuki, Kazunobu; Watanabe, Yuri; Takahashi, Yusuke; Kobayashi, Sakiko; Watanabe, Shiho; Ogawa, Shuhei; Kotani, Motoko; Kozono, Haruo; Tanabe, Kazunari; Abe, Ryo

    2009-03-20

    In order to fully understand T cell-mediated immunity, the mechanisms that regulate clonal expansion and cytokine production by CD4{sup +} antigen-specific effector T cells in response to a wide range of antigenic stimulation needs clarification. For this purpose, panels of antigen-specific CD4{sup +} T cell clones with different thresholds for antigen-induced proliferation were generated by repeated stimulation with high- or low-dose antigen. Differences in antigen sensitivities did not correlate with expression of TCR, CD4, adhesion or costimulatory molecules. There was no significant difference in antigen-dependent cytokine production by TG40 cells transfected with TCR obtained from either high- or low-dose-responding T cell clones, suggesting that the affinity of TCRs for their ligands is not primary determinant of T cell antigen reactivity. The proliferative responses of all T cell clones to both peptide stimulation and to TCR{beta} crosslinking revealed parallel dose-response curves. These results suggest that the TCR signal strength of effector T cells and threshold of antigen reactivity is determined by an intrinsic property, such as the TCR signalosome and/or intracellular signaling machinery. Finally, the antigen responses of high- and low-peptide-responding T cell clones reveal that clonal expansion and cytokine production of effector T cells occur independently of antigen concentration. Based on these results, the mechanisms underlying selection of high 'avidity' effector and memory T cells in response to pathogen are discussed.

  1. Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice.

    PubMed

    Cheung, Alice M S; Nguyen, Long V; Carles, Annaick; Beer, Philip; Miller, Paul H; Knapp, David J H F; Dhillon, Kiran; Hirst, Martin; Eaves, Connie J

    2013-10-31

    Human cord blood (CB) offers an attractive source of cells for clinical transplants because of its rich content of cells with sustained repopulating ability in spite of an apparent deficiency of cells with rapid reconstituting ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain poorly understood. To begin to address this question, we exposed CD34+ CB cells to a library of barcoded lentiviruses and used massively parallel sequencing to quantify the clonal distributions of lymphoid and myeloid cells subsequently detected in sequential marrow aspirates obtained from 2 primary NOD/SCID-IL2Rγ(-/-) mice, each transplanted with ∼10(5) of these cells, and for another 6 months in 2 secondary recipients. Of the 196 clones identified, 68 were detected at 4 weeks posttransplant and were often lympho-myeloid. The rest were detected later, after variable periods up to 13 months posttransplant, but with generally increasing stability throughout time, and they included clones in which different lineages were detected. However, definitive evidence of individual cells capable of generating T-, B-, and myeloid cells, for over a year, and self-renewal of this potential was also obtained. These findings highlight the caveats and utility of this model to analyze human hematopoietic stem cell control in vivo.

  2. Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice

    PubMed Central

    Cheung, Alice M. S.; Nguyen, Long V.; Carles, Annaick; Beer, Philip; Miller, Paul H.; Knapp, David J. H. F.; Dhillon, Kiran; Hirst, Martin

    2013-01-01

    Human cord blood (CB) offers an attractive source of cells for clinical transplants because of its rich content of cells with sustained repopulating ability in spite of an apparent deficiency of cells with rapid reconstituting ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain poorly understood. To begin to address this question, we exposed CD34+ CB cells to a library of barcoded lentiviruses and used massively parallel sequencing to quantify the clonal distributions of lymphoid and myeloid cells subsequently detected in sequential marrow aspirates obtained from 2 primary NOD/SCID-IL2Rγ−/− mice, each transplanted with ∼105 of these cells, and for another 6 months in 2 secondary recipients. Of the 196 clones identified, 68 were detected at 4 weeks posttransplant and were often lympho-myeloid. The rest were detected later, after variable periods up to 13 months posttransplant, but with generally increasing stability throughout time, and they included clones in which different lineages were detected. However, definitive evidence of individual cells capable of generating T-, B-, and myeloid cells, for over a year, and self-renewal of this potential was also obtained. These findings highlight the caveats and utility of this model to analyze human hematopoietic stem cell control in vivo. PMID:24030380

  3. Parallel algorithm development

    SciTech Connect

    Adams, T.F.

    1996-06-01

    Rapid changes in parallel computing technology are causing significant changes in the strategies being used for parallel algorithm development. One approach is simply to write computer code in a standard language like FORTRAN 77 or with the expectation that the compiler will produce executable code that will run in parallel. The alternatives are: (1) to build explicit message passing directly into the source code; or (2) to write source code without explicit reference to message passing or parallelism, but use a general communications library to provide efficient parallel execution. Application of these strategies is illustrated with examples of codes currently under development.

  4. Invasive clonal plant species have a greater root-foraging plasticity than non-invasive ones.

    PubMed

    Keser, Lidewij H; Dawson, Wayne; Song, Yao-Bin; Yu, Fei-Hai; Fischer, Markus; Dong, Ming; van Kleunen, Mark

    2014-03-01

    Clonality is frequently positively correlated with plant invasiveness, but which aspects of clonality make some clonal species more invasive than others is not known. Due to their spreading growth form, clonal plants are likely to experience spatial heterogeneity in nutrient availability. Plasticity in allocation of biomass to clonal growth organs and roots may allow these plants to forage for high-nutrient patches. We investigated whether this foraging response is stronger in species that have become invasive than in species that have not. We used six confamilial pairs of native European clonal plant species differing in invasion success in the USA. We grew all species in large pots under homogeneous or heterogeneous nutrient conditions in a greenhouse, and compared their nutrient-foraging response and performance. Neither invasive nor non-invasive species showed significant foraging responses to heterogeneity in clonal growth organ biomass or in aboveground biomass of clonal offspring. Invasive species had, however, a greater positive foraging response in terms of root and belowground biomass than non-invasive species. Invasive species also produced more total biomass. Our results suggest that the ability for strong root foraging is among the characteristics promoting invasiveness in clonal plants.

  5. How Past and Present Influence the Foraging of Clonal Plants?

    PubMed Central

    Louâpre, Philipe; Bittebière, Anne-Kristel; Clément, Bernard; Pierre, Jean-Sébastien; Mony, Cendrine

    2012-01-01

    Clonal plants spreading horizontally and forming a network structure of ramets exhibit complex growth patterns to maximize resource uptake from the environment. They respond to spatial heterogeneity by changing their internode length or branching frequency. Ramets definitively root in the soil but stay interconnected for a varying period of time thus allowing an exchange of spatial and temporal information. We quantified the foraging response of clonal plants depending on the local soil quality sampled by the rooting ramet (i.e. the present information) and the resource variability sampled by the older ramets (i.e. the past information). We demonstrated that two related species, Potentilla reptans and P. anserina, responded similarly to the local quality of their environment by decreasing their internode length in response to nutrient-rich soil. Only P. reptans responded to resource variability by decreasing its internode length. In both species, the experience acquired by older ramets influenced the plastic response of new rooted ramets: the internode length between ramets depended not only on the soil quality locally sampled but also on the soil quality previously sampled by older ramets. We quantified the effect of the information perceived at different time and space on the foraging behavior of clonal plants by showing a non-linear response of the ramet rooting in the soil of a given quality. These data suggest that the decision to grow a stolon or to root a ramet at a given distance from the older ramet results from the integration of the past and present information about the richness and the variability of the environment. PMID:22675539

  6. Parallel Atomistic Simulations

    SciTech Connect

    HEFFELFINGER,GRANT S.

    2000-01-18

    Algorithms developed to enable the use of atomistic molecular simulation methods with parallel computers are reviewed. Methods appropriate for bonded as well as non-bonded (and charged) interactions are included. While strategies for obtaining parallel molecular simulations have been developed for the full variety of atomistic simulation methods, molecular dynamics and Monte Carlo have received the most attention. Three main types of parallel molecular dynamics simulations have been developed, the replicated data decomposition, the spatial decomposition, and the force decomposition. For Monte Carlo simulations, parallel algorithms have been developed which can be divided into two categories, those which require a modified Markov chain and those which do not. Parallel algorithms developed for other simulation methods such as Gibbs ensemble Monte Carlo, grand canonical molecular dynamics, and Monte Carlo methods for protein structure determination are also reviewed and issues such as how to measure parallel efficiency, especially in the case of parallel Monte Carlo algorithms with modified Markov chains are discussed.

  7. Clonal distribution of multidrug-resistant Enterobacter cloacae.

    PubMed

    Girlich, Delphine; Poirel, Laurent; Nordmann, Patrice

    2015-04-01

    A multilocus sequence typing (MLST) scheme including 7 housekeeping genes was used to evaluate whether the current spread of multidrug-resistant Enterobacter cloacae isolates worldwide might be associated to specific successful clones. Fifty E. cloacae clinical isolates of worldwide origin, with various β-lactamase content, and recovered at different periods of time were studied. Forty-four sequence types were identified, highlighting a high clonal diversity with 3 main lineages. This study revealed that a precise identification of the isolates by sequencing of the chromosomal ampC gene of E. cloacae would provide a significant added value to improve the reliability of the MLST scheme.

  8. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains

    PubMed Central

    Teatero, Sarah; Patel, Samir N.

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  9. Plant traits and ecosystem effects of clonality: a new research agenda

    PubMed Central

    Cornelissen, Johannes H. C.; Song, Yao-Bin; Yu, Fei-Hai; Dong, Ming

    2014-01-01

    Background Clonal plants spread laterally by spacers between their ramets (shoot–root units); these spacers can transport and store resources. While much is known about how clonality promotes plant fitness, we know little about how different clonal plants influence ecosystem functions related to carbon, nutrient and water cycling. Approach The response–effect trait framework is used to formulate hypotheses about the impact of clonality on ecosystems. Central to this framework is the degree of correspondence between interspecific variation in clonal ‘response traits’ that promote plant fitness and interspecific variation in ‘effect traits’, which define a plant's potential effect on ecosystem functions. The main example presented to illustrate this concept concerns clonal traits of vascular plant species that determine their lateral extension patterns. In combination with the different degrees of decomposability of litter derived from their spacers, leaves, roots and stems, these clonal traits should determine associated spatial and temporal patterns in soil organic matter accumulation, nutrient availability and water retention. Conclusions This review gives some concrete pointers as to how to implement this new research agenda through a combination of (1) standardized screening of predominant species in ecosystems for clonal response traits and for effect traits related to carbon, nutrient and water cycling; (2) analysing the overlap between variation in these response traits and effect traits across species; (3) linking spatial and temporal patterns of clonal species in the field to those for soil properties related to carbon, nutrient and water stocks and dynamics; and (4) studying the effects of biotic interactions and feedbacks between resource heterogeneity and clonality. Linking these to environmental changes may help us to better understand and predict the role of clonal plants in modulating impacts of climate change and human activities on

  10. Escherichia coli ST131, an Intriguing Clonal Group

    PubMed Central

    Bertrand, Xavier; Madec, Jean-Yves

    2014-01-01

    SUMMARY In 2008, a previously unknown Escherichia coli clonal group, sequence type 131 (ST131), was identified on three continents. Today, ST131 is the predominant E. coli lineage among extraintestinal pathogenic E. coli (ExPEC) isolates worldwide. Retrospective studies have suggested that it may originally have risen to prominence as early as 2003. Unlike other classical group B2 ExPEC isolates, ST131 isolates are commonly reported to produce extended-spectrum β-lactamases, such as CTX-M-15, and almost all are resistant to fluoroquinolones. Moreover, ST131 E. coli isolates are considered to be truly pathogenic, due to the spectrum of infections they cause in both community and hospital settings and the large number of virulence-associated genes they contain. ST131 isolates therefore seem to contradict the widely held view that high levels of antimicrobial resistance are necessarily associated with a fitness cost leading to a decrease in pathogenesis. Six years after the first description of E. coli ST131, this review outlines the principal traits of ST131 clonal group isolates, based on the growing body of published data, and highlights what is currently known and what we need to find out to provide public health authorities with better information to help combat ST131. PMID:24982321

  11. Clonality and intracellular polyploidy in virus evolution and pathogenesis.

    PubMed

    Perales, Celia; Moreno, Elena; Domingo, Esteban

    2015-07-21

    In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.

  12. Quantum-inspired immune clonal algorithm for global optimization.

    PubMed

    Jiao, Licheng; Li, Yangyang; Gong, Maoguo; Zhang, Xiangrong

    2008-10-01

    Based on the concepts and principles of quantum computing, a novel immune clonal algorithm, called a quantum-inspired immune clonal algorithm (QICA), is proposed to deal with the problem of global optimization. In QICA, the antibody is proliferated and divided into a set of subpopulation groups. The antibodies in a subpopulation group are represented by multistate gene quantum bits. In the antibody's updating, the general quantum rotation gate strategy and the dynamic adjusting angle mechanism are applied to accelerate convergence. The quantum not gate is used to realize quantum mutation to avoid premature convergences. The proposed quantum recombination realizes the information communication between subpopulation groups to improve the search efficiency. Theoretical analysis proves that QICA converges to the global optimum. In the first part of the experiments, 10 unconstrained and 13 constrained benchmark functions are used to test the performance of QICA. The results show that QICA performs much better than the other improved genetic algorithms in terms of the quality of solution and computational cost. In the second part of the experiments, QICA is applied to a practical problem (i.e., multiuser detection in direct-sequence code-division multiple-access systems) with a satisfying result.

  13. Age-related cancer mutations associated with clonal hematopoietic expansion

    PubMed Central

    Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li

    2015-01-01

    Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion. PMID:25326804

  14. The genome of the clonal raider ant Cerapachys biroi

    PubMed Central

    Oxley, Peter R.; Ji, Lu; Fetter-Pruneda, Ingrid; McKenzie, Sean K.; Li, Cai; Hu, Haofu; Zhang, Guojie; Kronauer, Daniel J.C.

    2014-01-01

    Summary Social insects are important models for social evolution and behavior. However, in many species experimental control over important factors that regulate division of labor, such as genotype and age, is limited [1, 2]. Furthermore, most species have fixed queen and worker castes, making it difficult to establish causality between the molecular mechanisms that underlie reproductive division of labor, the hallmark of insect societies [3]. Here we present the genome of the queenless clonal raider ant Cerapachys biroi, a powerful new study system that does not suffer from these constraints. Using cytology and RAD-Seq, we show that C. biroi reproduces via automixis with central fusion and that heterozygosity is lost extremely slowly. As a consequence, nestmates are almost clonally related (r=0.996). Workers in C. biroi colonies synchronously alternate between reproduction and brood care, and young workers eclose in synchronized cohorts. We show that genes associated with division of labor in other social insects are conserved in C. biroi and dynamically regulated during the colony cycle. With unparalleled experimental control over an individual’s genotype and age, and the ability to induce reproduction and brood care [4, 5], C. biroi has great potential to illuminate the molecular regulation of division of labor. PMID:24508170

  15. Single-cell mutational profiling and clonal phylogeny in cancer

    PubMed Central

    Potter, Nicola E.; Ermini, Luca; Papaemmanuil, Elli; Cazzaniga, Giovanni; Vijayaraghavan, Gowri; Titley, Ian; Ford, Anthony; Campbell, Peter; Kearney, Lyndal; Greaves, Mel

    2013-01-01

    The development of cancer is a dynamic evolutionary process in which intraclonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intraclonal genetic architectures have major implications for biopsy-based prognosis and for targeted therapy. High-depth, next-generation sequencing (NGS) efficiently captures the mutational load of individual tumors or biopsies. But, being a snapshot portrait of total DNA, it disguises the fundamental features of subclonal variegation of genetic lesions and of clonal phylogeny. Single-cell genetic profiling provides a potential resolution to this problem, but methods developed to date all have limitations. We present a novel solution to this challenge using leukemic cells with known mutational spectra as a tractable model. DNA from flow-sorted single cells is screened using multiplex targeted Q-PCR within a microfluidic platform allowing unbiased single-cell selection, high-throughput, and comprehensive analysis for all main varieties of genetic abnormalities: chimeric gene fusions, copy number alterations, and single-nucleotide variants. We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies. PMID:24056532

  16. Rapid contemporary evolution and clonal food web dynamics.

    PubMed

    Jones, Laura E; Becks, Lutz; Ellner, Stephen P; Hairston, Nelson G; Yoshida, Takehito; Fussmann, Gregor F

    2009-06-12

    Character evolution that affects ecological community interactions often occurs contemporaneously with temporal changes in population size, potentially altering the very nature of those dynamics. Such eco-evolutionary processes may be most readily explored in systems with short generations and simple genetics. Asexual and cyclically parthenogenetic organisms such as microalgae, cladocerans and rotifers, which frequently dominate freshwater plankton communities, meet these requirements. Multiple clonal lines can coexist within each species over extended periods, until either fixation occurs or a sexual phase reshuffles the genetic material. When clones differ in traits affecting interspecific interactions, within-species clonal dynamics can have major effects on the population dynamics. We first consider a simple predator-prey system with two prey genotypes, parametrized with data from a well-studied experimental system, and explore how the extent of differences in defence against predation within the prey population determine dynamic stability versus instability of the system. We then explore how increased potential for evolution affects the community dynamics in a more general community model with multiple predator and multiple prey genotypes. These examples illustrate how microevolutionary 'details' that enhance or limit the potential for heritable phenotypic change can have significant effects on contemporaneous community-level dynamics and the persistence and coexistence of species.

  17. The evolution of two mutations during clonal expansion.

    PubMed

    Haeno, Hiroshi; Iwasa, Yoh; Michor, Franziska

    2007-12-01

    Knudson's two-hit hypothesis proposes that two genetic changes in the RB1 gene are the rate-limiting steps of retinoblastoma. In the inherited form of this childhood eye cancer, only one mutation emerges during somatic cell divisions while in sporadic cases, both alleles of RB1 are inactivated in the growing retina. Sporadic retinoblastoma serves as an example of a situation in which two mutations are accumulated during clonal expansion of a cell population. Other examples include evolution of resistance against anticancer combination therapy and inactivation of both alleles of a metastasis-suppressor gene during tumor growth. In this article, we consider an exponentially growing population of cells that must evolve two mutations to (i) evade treatment, (ii) make a step toward (invasive) cancer, or (iii) display a disease phenotype. We calculate the probability that the population has evolved both mutations before it reaches a certain size. This probability depends on the rates at which the two mutations arise; the growth and death rates of cells carrying none, one, or both mutations; and the size the cell population reaches. Further, we develop a formula for the expected number of cells carrying both mutations when the final population size is reached. Our theory establishes an understanding of the dynamics of two mutations during clonal expansion.

  18. Clonal population structure of Colombian sylvatic Trypanosoma cruzi.

    PubMed

    Márquez, E; Arcos-Burgos, M; Triana, O; Moreno, J; Jaramillo, N

    1998-12-01

    Isoenzyme variability and evidence of genetic exchange were evaluated in 75 wild stocks of Trypanosoma cruzi obtained from different hosts from 5 geographical regions within the endemic area in Colombia. Cluster analysis of genetic variability was attempted. Thirty-three multilocus enzyme genotypes (clonets) were identified from 75 stocks, 27 of which clustered with zymodeme Z1 and 6 with zymodeme Z3. Two stocks isolated from human infections showed the potential risk to rural communities in Colombia. The stocks exhibited departures from Hardy-Weinberg expectations, including both fixed heterozygote and fixed homozygote demes, where both segregation and recombination were absent. To inspect for population subdivision that might falsely imply clonality in these stocks, Wright's F statistics were calculated. Theta values (Fst) were significantly different from 0 when 33 clonets, 27 Z1-like clonets, and 5 geographical subpopulations were compared; thus, a significant amount of divergence has occurred between and within them. In addition, linkage disequilibrium was detected for most possible pairwise comparisons of loci. In conclusion, the above results all support a scenario of long-term clonal evolution in Colombian sylvatic T. cruzi populations.

  19. Parallel digital forensics infrastructure.

    SciTech Connect

    Liebrock, Lorie M.; Duggan, David Patrick

    2009-10-01

    This report documents the architecture and implementation of a Parallel Digital Forensics infrastructure. This infrastructure is necessary for supporting the design, implementation, and testing of new classes of parallel digital forensics tools. Digital Forensics has become extremely difficult with data sets of one terabyte and larger. The only way to overcome the processing time of these large sets is to identify and develop new parallel algorithms for performing the analysis. To support algorithm research, a flexible base infrastructure is required. A candidate architecture for this base infrastructure was designed, instantiated, and tested by this project, in collaboration with New Mexico Tech. Previous infrastructures were not designed and built specifically for the development and testing of parallel algorithms. With the size of forensics data sets only expected to increase significantly, this type of infrastructure support is necessary for continued research in parallel digital forensics. This report documents the implementation of the parallel digital forensics (PDF) infrastructure architecture and implementation.

  20. Introduction to Parallel Computing

    DTIC Science & Technology

    1992-05-01

    Topology C, Ada, C++, Data-parallel FORTRAN, 2D mesh of node boards, each node FORTRAN-90 (late 1992) board has 1 application processor Devopment Tools ...parallel machines become the wave of the present, tools are increasingly needed to assist programmers in creating parallel tasks and coordinating...their activities. Linda was designed to be such a tool . Linda was designed with three important goals in mind: to be portable, efficient, and easy to use

  1. Parallel Wolff Cluster Algorithms

    NASA Astrophysics Data System (ADS)

    Bae, S.; Ko, S. H.; Coddington, P. D.

    The Wolff single-cluster algorithm is the most efficient method known for Monte Carlo simulation of many spin models. Due to the irregular size, shape and position of the Wolff clusters, this method does not easily lend itself to efficient parallel implementation, so that simulations using this method have thus far been confined to workstations and vector machines. Here we present two parallel implementations of this algorithm, and show that one gives fairly good performance on a MIMD parallel computer.

  2. PCLIPS: Parallel CLIPS

    NASA Technical Reports Server (NTRS)

    Hall, Lawrence O.; Bennett, Bonnie H.; Tello, Ivan

    1994-01-01

    A parallel version of CLIPS 5.1 has been developed to run on Intel Hypercubes. The user interface is the same as that for CLIPS with some added commands to allow for parallel calls. A complete version of CLIPS runs on each node of the hypercube. The system has been instrumented to display the time spent in the match, recognize, and act cycles on each node. Only rule-level parallelism is supported. Parallel commands enable the assertion and retraction of facts to/from remote nodes working memory. Parallel CLIPS was used to implement a knowledge-based command, control, communications, and intelligence (C(sup 3)I) system to demonstrate the fusion of high-level, disparate sources. We discuss the nature of the information fusion problem, our approach, and implementation. Parallel CLIPS has also be used to run several benchmark parallel knowledge bases such as one to set up a cafeteria. Results show from running Parallel CLIPS with parallel knowledge base partitions indicate that significant speed increases, including superlinear in some cases, are possible.

  3. Application Portable Parallel Library

    NASA Technical Reports Server (NTRS)

    Cole, Gary L.; Blech, Richard A.; Quealy, Angela; Townsend, Scott

    1995-01-01

    Application Portable Parallel Library (APPL) computer program is subroutine-based message-passing software library intended to provide consistent interface to variety of multiprocessor computers on market today. Minimizes effort needed to move application program from one computer to another. User develops application program once and then easily moves application program from parallel computer on which created to another parallel computer. ("Parallel computer" also include heterogeneous collection of networked computers). Written in C language with one FORTRAN 77 subroutine for UNIX-based computers and callable from application programs written in C language or FORTRAN 77.

  4. Parallel Algorithms and Patterns

    SciTech Connect

    Robey, Robert W.

    2016-06-16

    This is a powerpoint presentation on parallel algorithms and patterns. A parallel algorithm is a well-defined, step-by-step computational procedure that emphasizes concurrency to solve a problem. Examples of problems include: Sorting, searching, optimization, matrix operations. A parallel pattern is a computational step in a sequence of independent, potentially concurrent operations that occurs in diverse scenarios with some frequency. Examples are: Reductions, prefix scans, ghost cell updates. We only touch on parallel patterns in this presentation. It really deserves its own detailed discussion which Gabe Rockefeller would like to develop.

  5. Polymerase chain reaction (PCR) detection of B cell clonality in Sjögren's syndrome patients: a diagnostic tool of clonal expansion

    PubMed Central

    Guzmán, L M; Castillo, D; Aguilera, S O

    2010-01-01

    Sjögren's syndrome (SS) is an autoimmune disease characterized by clonal B cell attack of the exocrine glands and dysregulated expression of B cell-activating factor (BAFF). Based upon the current data of increased rates of lymphoid malignancy, as non-Hodgkin's lymphoma (NHL) is associated with SS, we propose the detection of clonal rearrangements of immunoglobulin heavy chain (IgH) gene in those patients as a predictor of malignant clonal expansion. To test our proposal, we examined the IgH clonal rearrangements in SS patients (60) and healthy control subjects (42) having chronic non-specific sialadenitis, to determine the presence of clonal B cells in minor labial salivary glands (MSG) of SS patients. Clonal B cell expansion was assessed by two polymerase chain reaction (PCR) assays: (i) semi-nested PCR, against sequences encoding framework regions FR3, FR2 and FR1c of the variable chain IgH gene in B cells present in the MSG infiltrate; and (ii) the PCR–enzyme-linked immunosorbent assay (ELISA) technique, against the major and minor breakpoint regions of the Bcl-2 oncogene coupled with a variable segment of the IgH to assess the Bcl-2/JH translocation. When FR3, FR2 and FR1c primers were employed, we detected B cell monoclonality in 87% of the SS patients and 19% of the control subjects. The association between inflammation severity of the MSG pattern and the presence of B cell clonality was found to be statistically significant (P < 0·01). We concluded that the presence of B cell clonality in MSG can be used as a index of an altered microenvironment favouring the development of lymphoma in SS patients. PMID:20408860

  6. Virulence, sporulation, and elicitin production in three clonal lineages of Phytophthora ramorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora ramorum populations are clonal and consist of three lineages. Recent studies have shown that the clonal lineages may have varying degrees of aggressiveness on some host species, such as Quercus rubra. In this study, we examined virulence, sporulation and elicitin production of five P. ...

  7. Faster clonal turnover in high-infection habitats provides evidence for parasite-mediated selection.

    PubMed

    Paczesniak, D; Adolfsson, S; Liljeroos, K; Klappert, K; Lively, C M; Jokela, J

    2014-02-01

    According to the Red Queen hypothesis for sex, parasite-mediated selection against common clones counterbalances the reproductive advantage of asexual lineages, which would otherwise outcompete sexual conspecifics. Such selection on the clonal population is expected to lead to a faster clonal turnover in habitats where selection by parasites is stronger. We tested this prediction by comparing the genetic structure of clonal and sexual populations of freshwater snail Potamopyrgus antipodarum between years 2003 and 2007 in three depth-specific habitats in Lake Alexandrina (South Island, New Zealand). These habitats differ in the risk of infection by castrating trematodes and in the relative proportion of sexual individuals. As predicted, we found that the clonal structure changed significantly in shallow and mid-water habitats, where prevalence of infection was high, but not in the deep habitat, where parasite prevalence was low. Additionally, we found that both clonal diversity and evenness of the asexual population declined in the shallow habitat. In contrast, the genetic structure (based on F-statistics) of the coexisting sexual population did not change, which suggests that the change in the clonal structure cannot be related to genetic changes in the sexual population. Finally, the frequency of sexuals had no effect on the diversity of the sympatric clonal population. Taken together, our results show a more rapid clonal turnover in high-infection habitats, which gives support for the Red Queen hypothesis for sex.

  8. Novel R tools for analysis of genome-wide population genetic data with emphasis on clonality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To gain a detailed understanding of how plant microbes evolve and adapt to hosts, pesticides, and other factors, knowledge of the population dynamics and evolutionary history of populations is crucial. Plant pathogen populations are often clonal or partially clonal which requires different analytica...

  9. Standardizing the Nomenclature for Clonal Lineages of the Sudden Oak Death Pathogen, Phytophthora ramorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora ramorum, the causal agent of sudden oak death and ramorum blight, is known to exist as three distinct clonal lineages based on a range of molecular marker systems. However, in the recent literature there exists no consensus on naming of lineages. Here we name clonal lineages of P. ramor...

  10. A novel clonality assay for the assessment of canine T cell proliferations.

    PubMed

    Keller, Stefan M; Moore, Peter F

    2012-01-15

    Polymerase chain reaction (PCR) based clonality assays are an important tool to differentiate neoplastic from reactive lymphocyte populations. A recent description of the canine T cell receptor γ locus identified a large number of formerly unknown genes, and determined the locus topology consisting of 8 cassettes with up to 3 variable (V) genes, 2 joining (J) genes and one constant (C) gene each. Given that these data were not available when existing canine T cell clonality assays were developed, it is likely that they will fail to detect a subset of clonal lymphocyte populations. The objective of this study was to gauge the potential of canine T cell clonality assays to detect all rearranged T cell receptor γ genes and to develop an improved clonality assay. The primer sequences of existing clonality assays were aligned to the reference sequences of all rearranged genes and genes were scored as to the likelihood of being recognized by a primer. All four assays likely recognized subgroup Vγ2 and Vγ6 genes but 3 out of 4 assays were unlikely to detect subgroup Vγ3 and Vγ7 genes. All assays likely recognized Jγx-2 genes, but only two assays were likely to detect most Jγx-1 genes. Two assays had forward primers located as close as four nucleotides to the junctional region. A new multiplex PCR was designed with all primers combined in a single tube. An alternative primer set allowed identification of variable gene usage through gene specific forward primers. The coverage of all rearranged genes facilitated the detection of multiple clonal rearrangements per neoplastic sample. The new assay detected clonal DNA at a concentration of 5% within polyclonal background but detection thresholds were dependent on the gene usage of clonal rearrangements as well as the position of the clonal peak in respect to the polyclonal background. The new multiplex assay recognized 12/12 (100%) of confirmed neoplastic samples as compared to 2/12 (17%) by an existing assay. On a

  11. SNP-based differentiation of Phytophthora infestans clonal lineages using locked nucleic acid probes and high resolution melt analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytophthora infestans, the cause of the devastating late blight disease of potato and tomato, exhibits a clonal reproductive lifestyle in North America. Phenotypes such as fungicide sensitivity and host preference are conserved among individuals within clonal lineages, while substantial phenotypic ...

  12. Analysis of allelic expression patterns in clonal somatic cells by single-cell RNA-seq.

    PubMed

    Reinius, Björn; Mold, Jeff E; Ramsköld, Daniel; Deng, Qiaolin; Johnsson, Per; Michaëlsson, Jakob; Frisén, Jonas; Sandberg, Rickard

    2016-11-01

    Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8(+) T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells.

  13. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

    PubMed Central

    McGranahan, Nicholas; Furness, Andrew J. S.; Rosenthal, Rachel; Ramskov, Sofie; Lyngaa, Rikke; Saini, Sunil Kumar; Jamal-Hanjani, Mariam; Wilson, Gareth A.; Birkbak, Nicolai J.; Hiley, Crispin T.; Watkins, Thomas B. K.; Shafi, Seema; Murugaesu, Nirupa; Mitter, Richard; Akarca, Ayse U.; Linares, Joseph; Marafioti, Teresa; Henry, Jake Y.; Van Allen, Eliezer M.; Miao, Diana; Schilling, Bastian; Schadendorf, Dirk; Garraway, Levi A.; Makarov, Vladimir; Rizvi, Naiyer A.; Snyder, Alexandra; Hellmann, Matthew D.; Merghoub, Taha; Wolchok, Jedd D.; Shukla, Sachet A.; Wu, Catherine J.; Peggs, Karl S.; Chan, Timothy A.; Hadrup, Sine R.; Quezada, Sergio A.; Swanton, Charles

    2016-01-01

    As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8+ tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens. PMID:26940869

  14. Scaling of processes shaping the clonal dynamics and genetic mosaic of seagrasses through temporal genetic monitoring

    PubMed Central

    Becheler, R; Benkara, E; Moalic, Y; Hily, C; Arnaud-Haond, S

    2014-01-01

    Theoretically, the dynamics of clonal and genetic diversities of clonal plant populations are strongly influenced by the competition among clones and rate of seedling recruitment, but little empirical assessment has been made of such dynamics through temporal genetic surveys. We aimed to quantify 3 years of evolution in the clonal and genetic composition of Zostera marina meadows, comparing parameters describing clonal architecture and genetic diversity at nine microsatellite markers. Variations in clonal structure revealed a decrease in the evenness of ramet distribution among genets. This illustrates the increasing dominance of some clonal lineages (multilocus lineages, MLLs) in populations. Despite the persistence of these MLLs over time, genetic differentiation was much stronger in time than in space, at the local scale. Contrastingly with the short-term evolution of clonal architecture, the patterns of genetic structure and genetic diversity sensu stricto (that is, heterozygosity and allelic richness) were stable in time. These results suggest the coexistence of (i) a fine grained (at the scale of a 20 × 30 m quadrat) stable core of persistent genets originating from an initial seedling recruitment and developing spatial dominance through clonal elongation; and (ii) a local (at the scale of the meadow) pool of transient genets subjected to annual turnover. This simultaneous occurrence of initial and repeated recruitment strategies highlights the different spatial scales at which distinct evolutionary drivers and mating systems (clonal competition, clonal growth, propagule dispersal and so on) operate to shape the dynamics of populations and the evolution of polymorphism in space and time. PMID:24022498

  15. Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X chromosomal probe.

    PubMed Central

    Fey, M F; Peter, H J; Hinds, H L; Zimmermann, A; Liechti-Gallati, S; Gerber, H; Studer, H; Tobler, A

    1992-01-01

    The clonality of human tumors can be studied by X inactivation/methylation analysis in female patients heterozygous for X-linked DNA polymorphisms. We present a detailed study on clonal tumor analysis with M27 beta, a highly informative probe detecting a polymorphic X chromosomal locus, DXS255. The polymorphism detected at this locus is due to variable numbers of tandem repeats. The rate of constitutional heterozygosity detected by M27 beta was 88%. Normal tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal, patterns. Nonrandom clonal X inactivation was detected in all 22 malignant neoplasms that had been shown to be clonal by other DNA markers, such as antigen receptor gene rearrangements or clonal loss of heterozygosity at 17p and other loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X inactivation patterns. Comparison of blood leukocytes and normal tissue indicated that in a given individual, X inactivation patterns may be tissue specific. M27 beta was used to study the clonal composition of 13 benign thyroid nodules from 12 multinodular goiters with rapid recent growth, traditionally termed "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case of Graves' goiter were not, indicating that some, but not all, such thyroid nodules may represent true clonal neoplasms. The M27 beta probe permits one to study the clonal composition by the X inactivation approach of a wide variety of solid tumors from most female patients. As a control, normal tissue homologous to the tumor type of interest is preferable to DNA from blood leukocytes, since the latter may show nonrandom X inactivation patterns in a fairly high proportion of cases. M27 beta may, therefore, be of limited use for the clonal analysis of neoplasms derived from hematopoietic cells. Images PMID:1349026

  16. Demographic consequences of greater clonal than sexual reproduction in Dicentra canadensis.

    PubMed

    Lin, Chia-Hua; Miriti, Maria N; Goodell, Karen

    2016-06-01

    Clonality is a widespread life history trait in flowering plants that may be essential for population persistence, especially in environments where sexual reproduction is unpredictable. Frequent clonal reproduction, however, could hinder sexual reproduction by spatially aggregating ramets that compete with seedlings and reduce inter-genet pollination. Nevertheless, the role of clonality in relation to variable sexual reproduction in population dynamics is often overlooked. We combined population matrix models and pollination experiments to compare the demographic contributions of clonal and sexual reproduction in three Dicentra canadensis populations, one in a well-forested landscape and two in isolated forest remnants. We constructed stage-based transition matrices from 3 years of census data to evaluate annual population growth rates, λ. We used loop analysis to evaluate the relative contribution of different reproductive pathways to λ. Despite strong temporal and spatial variation in seed set, populations generally showed stable growth rates. Although we detected some pollen limitation of seed set, manipulative pollination treatments did not affect population growth rates. Clonal reproduction contributed significantly more than sexual reproduction to population growth in the forest remnants. Only at the well-forested site did sexual reproduction contribute as much as clonal reproduction to population growth. Flowering plants were more likely to transition to a smaller size class with reduced reproductive potential in the following year than similarly sized nonflowering plants, suggesting energy trade-offs between sexual and clonal reproduction at the individual level. Seed production had negligible effects on growth and tuber production of individual plants. Our results demonstrate that clonal reproduction is vital for population persistence in a system where sexual reproduction is unpredictable. The bias toward clonality may be driven by low fitness returns

  17. Parallel Lisp simulator

    SciTech Connect

    Weening, J.S.

    1988-05-01

    CSIM is a simulator for parallel Lisp, based on a continuation passing interpreter. It models a shared-memory multiprocessor executing programs written in Common Lisp, extended with several primitives for creating and controlling processes. This paper describes the structure of the simulator, measures its performance, and gives an example of its use with a parallel Lisp program.

  18. Parallel and Distributed Computing.

    DTIC Science & Technology

    1986-12-12

    program was devoted to parallel and distributed computing . Support for this part of the program was obtained from the present Army contract and a...Umesh Vazirani. A workshop on parallel and distributed computing was held from May 19 to May 23, 1986 and drew 141 participants. Keywords: Mathematical programming; Protocols; Randomized algorithms. (Author)

  19. Massively parallel mathematical sieves

    SciTech Connect

    Montry, G.R.

    1989-01-01

    The Sieve of Eratosthenes is a well-known algorithm for finding all prime numbers in a given subset of integers. A parallel version of the Sieve is described that produces computational speedups over 800 on a hypercube with 1,024 processing elements for problems of fixed size. Computational speedups as high as 980 are achieved when the problem size per processor is fixed. The method of parallelization generalizes to other sieves and will be efficient on any ensemble architecture. We investigate two highly parallel sieves using scattered decomposition and compare their performance on a hypercube multiprocessor. A comparison of different parallelization techniques for the sieve illustrates the trade-offs necessary in the design and implementation of massively parallel algorithms for large ensemble computers.

  20. Totally parallel multilevel algorithms

    NASA Technical Reports Server (NTRS)

    Frederickson, Paul O.

    1988-01-01

    Four totally parallel algorithms for the solution of a sparse linear system have common characteristics which become quite apparent when they are implemented on a highly parallel hypercube such as the CM2. These four algorithms are Parallel Superconvergent Multigrid (PSMG) of Frederickson and McBryan, Robust Multigrid (RMG) of Hackbusch, the FFT based Spectral Algorithm, and Parallel Cyclic Reduction. In fact, all four can be formulated as particular cases of the same totally parallel multilevel algorithm, which are referred to as TPMA. In certain cases the spectral radius of TPMA is zero, and it is recognized to be a direct algorithm. In many other cases the spectral radius, although not zero, is small enough that a single iteration per timestep keeps the local error within the required tolerance.

  1. Parallel computing works

    SciTech Connect

    Not Available

    1991-10-23

    An account of the Caltech Concurrent Computation Program (C{sup 3}P), a five year project that focused on answering the question: Can parallel computers be used to do large-scale scientific computations '' As the title indicates, the question is answered in the affirmative, by implementing numerous scientific applications on real parallel computers and doing computations that produced new scientific results. In the process of doing so, C{sup 3}P helped design and build several new computers, designed and implemented basic system software, developed algorithms for frequently used mathematical computations on massively parallel machines, devised performance models and measured the performance of many computers, and created a high performance computing facility based exclusively on parallel computers. While the initial focus of C{sup 3}P was the hypercube architecture developed by C. Seitz, many of the methods developed and lessons learned have been applied successfully on other massively parallel architectures.

  2. Clonal Evolution of Stem Cells in the Gastrointestinal Tract.

    PubMed

    Fink, Juergen; Koo, Bon-Kyoung

    The field of gastrointestinal epithelial stem cells is a rapidly developing area of adult stem cell research. The discovery of Lgr5(+) intestinal stem cells has enabled us to study many hidden aspects of the biology of gastrointestinal adult stem cells. Marked by Lgr5 and Troy, several novel endodermal stem cells have been identified in the gastrointestinal tract. A precise working model of stem cell propagation, dynamics, and plasticity has been revealed by a genetic labeling method, termed lineage tracing. This chapter introduces the reidentification of crypt base columnar cells as Lgr5(+) stem cells in the intestine. Subsequently, it will discuss dynamic clonal evolution and cellular plasticity in the intestinal stem cell zone, as well as in stem cell zones of stomach glands.

  3. Integrating Clonal Selection and Deterministic Sampling for Efficient Associative Classification

    PubMed Central

    Elsayed, Samir A. Mohamed; Rajasekaran, Sanguthevar; Ammar, Reda A.

    2013-01-01

    Traditional Associative Classification (AC) algorithms typically search for all possible association rules to find a representative subset of those rules. Since the search space of such rules may grow exponentially as the support threshold decreases, the rules discovery process can be computationally expensive. One effective way to tackle this problem is to directly find a set of high-stakes association rules that potentially builds a highly accurate classifier. This paper introduces AC-CS, an AC algorithm that integrates the clonal selection of the immune system along with deterministic data sampling. Upon picking a representative sample of the original data, it proceeds in an evolutionary fashion to populate only rules that are likely to yield good classification accuracy. Empirical results on several real datasets show that the approach generates dramatically less rules than traditional AC algorithms. In addition, the proposed approach is significantly more efficient than traditional AC algorithms while achieving a competitive accuracy. PMID:24500504

  4. Clonal mixtures of Salix - a control measure for rust

    SciTech Connect

    McCracken, A.R.; Dawson, W.M.; Allen C.Y.

    1996-12-31

    Willow grown in short rotation coppice can be used as a renewable energy source. However, disease caused by Melampsora epitea var. epitea can be a severely limiting factor on its productivity. Populations of this pathogen in N. Ireland have been shown to be composed of at least fourteen pathotypes. Pathotype composition was influenced by time, age and clone. Fungicides were unacceptable to control disease, therefore the use of clonal mixtures was employed as an alternative strategy. When grown in mixtures the onset of disease was delayed, its build up slowed and final levels reduced. This was reflected in increased yield. Current work investigating the effect of planting density and increasing mixture diversity indicates that neither have a major impact on disease.

  5. Clonal complexity in Mycobacterium tuberculosis can hamper diagnostic procedures.

    PubMed

    Pérez-Lago, Laura; Herranz, Marta; Navarro, Yurena; Ruiz Serrano, María Jesús; Miralles, Pilar; Bouza, Emilio; García-de-Viedma, Darío

    2017-02-15

    Clonal complexity is increasingly accepted in Mycobacterium tuberculosis infection, including mixed infections by ≥2 strains, which usually occur in settings with a high burden of tuberculosis and/or a high risk of overexposure to infected patients. Mixed infections can hamper diagnostic procedures: obtaining an accurate antibiogram is difficult when the susceptibility patterns of the strains differ. Here, we show how mixed infections can also prove challenging for other diagnostic procedures, even outside settings where mixed infections are traditionally expected. We show how an unnoticed mixed infection in an HIV-positive patient diagnosed in Madrid, Spain, with differences in the representativeness of the coinfecting strains in different sputum samples, markedly complicated the resolution of a laboratory cross-contamination false-positivity alert.

  6. FTO influences adipogenesis by regulating mitotic clonal expansion.

    PubMed

    Merkestein, Myrte; Laber, Samantha; McMurray, Fiona; Andrew, Daniel; Sachse, Gregor; Sanderson, Jeremy; Li, Mengdi; Usher, Samuel; Sellayah, Dyan; Ashcroft, Frances M; Cox, Roger D

    2015-04-17

    The fat mass and obesity-associated (FTO) gene plays a pivotal role in regulating body weight and fat mass; however, the underlying mechanisms are poorly understood. Here we show that primary adipocytes and mouse embryonic fibroblasts (MEFs) derived from FTO overexpression (FTO-4) mice exhibit increased potential for adipogenic differentiation, while MEFs derived from FTO knockout (FTO-KO) mice show reduced adipogenesis. As predicted from these findings, fat pads from FTO-4 mice fed a high-fat diet show more numerous adipocytes. FTO influences adipogenesis by regulating events early in adipogenesis, during the process of mitotic clonal expansion. The effect of FTO on adipogenesis appears to be mediated via enhanced expression of the pro-adipogenic short isoform of RUNX1T1, which enhanced adipocyte proliferation, and is increased in FTO-4 MEFs and reduced in FTO-KO MEFs. Our findings provide novel mechanistic insight into how upregulation of FTO leads to obesity.

  7. Genotypic richness predicts phenotypic variation in an endangered clonal plant.

    PubMed

    Evans, Suzanna M; Sinclair, Elizabeth A; Poore, Alistair G B; Bain, Keryn F; Vergés, Adriana

    2016-01-01

    Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species

  8. Genotypic richness predicts phenotypic variation in an endangered clonal plant

    PubMed Central

    Sinclair, Elizabeth A.; Poore, Alistair G.B.; Bain, Keryn F.; Vergés, Adriana

    2016-01-01

    Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species

  9. Negative plant soil feedback explaining ring formation in clonal plants.

    PubMed

    Cartenì, Fabrizio; Marasco, Addolorata; Bonanomi, Giuliano; Mazzoleni, Stefano; Rietkerk, Max; Giannino, Francesco

    2012-11-21

    Ring shaped patches of clonal plants have been reported in different environments, but the mechanisms underlying such pattern formation are still poorly explained. Water depletion in the inner tussocks zone has been proposed as a possible cause, although ring patterns have been also observed in ecosystems without limiting water conditions. In this work, a spatially explicit model is presented in order to investigate the role of negative plant-soil feedback as an additional explanation for ring formation. The model describes the dynamics of the plant biomass in the presence of toxicity produced by the decomposition of accumulated litter in the soil. Our model qualitatively reproduces the emergence of ring patterns of a single clonal plant species during colonisation of a bare substrate. The model admits two homogeneous stationary solutions representing bare soil and uniform vegetation cover which depend only on the ratio between the biomass death and growth rates. Moreover, differently from other plant spatial patterns models, but in agreement with real field observations of vegetation dynamics, we demonstrated that the pattern dynamics always lead to spatially homogeneous vegetation covers without creation of stable Turing patterns. Analytical results show that ring formation is a function of two main components, the plant specific susceptibility to toxic compounds released in the soil by the accumulated litter and the decay rate of these same compounds, depending on environmental conditions. These components act at the same time and their respective intensities can give rise to the different ring structures observed in nature, ranging from slight reductions of biomass in patch centres, to the appearance of marked rings with bare inner zones, as well as the occurrence of ephemeral waves of plant cover. Our results highlight the potential role of plant-soil negative feedback depending on decomposition processes for the development of transient vegetation patterns.

  10. The NAS parallel benchmarks

    NASA Technical Reports Server (NTRS)

    Bailey, David (Editor); Barton, John (Editor); Lasinski, Thomas (Editor); Simon, Horst (Editor)

    1993-01-01

    A new set of benchmarks was developed for the performance evaluation of highly parallel supercomputers. These benchmarks consist of a set of kernels, the 'Parallel Kernels,' and a simulated application benchmark. Together they mimic the computation and data movement characteristics of large scale computational fluid dynamics (CFD) applications. The principal distinguishing feature of these benchmarks is their 'pencil and paper' specification - all details of these benchmarks are specified only algorithmically. In this way many of the difficulties associated with conventional benchmarking approaches on highly parallel systems are avoided.

  11. Detecting truly clonal alterations from multi-region profiling of tumours

    PubMed Central

    Werner, Benjamin; Traulsen, Arne; Sottoriva, Andrea; Dingli, David

    2017-01-01

    Modern cancer therapies aim at targeting tumour-specific alterations, such as mutations or neo-antigens, and maximal treatment efficacy requires that targeted alterations are present in all tumour cells. Currently, treatment decisions are based on one or a few samples per tumour, creating uncertainty on whether alterations found in those samples are actually present in all tumour cells. The probability of classifying clonal versus sub-clonal alterations from multi-region profiling of tumours depends on the earliest phylogenetic branching event during tumour growth. By analysing 181 samples from 10 renal carcinoma and 11 colorectal cancers we demonstrate that the information gain from additional sampling falls onto a simple universal curve. We found that in colorectal cancers, 30% of alterations identified as clonal with one biopsy proved sub-clonal when 8 samples were considered. The probability to overestimate clonal alterations fell below 1% in 7/11 patients with 8 samples per tumour. In renal cell carcinoma, 8 samples reduced the list of clonal alterations by 40% with respect to a single biopsy. The probability to overestimate clonal alterations remained as high as 92% in 7/10 renal cancer patients. Furthermore, treatment was associated with more unbalanced tumour phylogenetic trees, suggesting the need of denser sampling of tumours at relapse. PMID:28344344

  12. African 2, a Clonal Complex of Mycobacterium bovis Epidemiologically Important in East Africa▿ †

    PubMed Central

    Berg, Stefan; Garcia-Pelayo, M. Carmen; Müller, Borna; Hailu, Elena; Asiimwe, Benon; Kremer, Kristin; Dale, James; Boniotti, M. Beatrice; Rodriguez, Sabrina; Hilty, Markus; Rigouts, Leen; Firdessa, Rebuma; Machado, Adelina; Mucavele, Custodia; Ngandolo, Bongo Nare Richard; Bruchfeld, Judith; Boschiroli, Laura; Müller, Annélle; Sahraoui, Naima; Pacciarini, Maria; Cadmus, Simeon; Joloba, Moses; van Soolingen, Dick; Michel, Anita L.; Djønne, Berit; Aranaz, Alicia; Zinsstag, Jakob; van Helden, Paul; Portaels, Françoise; Kazwala, Rudovick; Källenius, Gunilla; Hewinson, R. Glyn; Aseffa, Abraham; Gordon, Stephen V.; Smith, Noel H.

    2011-01-01

    We have identified a clonal complex of Mycobacterium bovis isolated at high frequency from cattle in Uganda, Burundi, Tanzania, and Ethiopia. We have named this related group of M. bovis strains the African 2 (Af2) clonal complex of M. bovis. Af2 strains are defined by a specific chromosomal deletion (RDAf2) and can be identified by the absence of spacers 3 to 7 in their spoligotype patterns. Deletion analysis of M. bovis isolates from Algeria, Mali, Chad, Nigeria, Cameroon, South Africa, and Mozambique did not identify any strains of the Af2 clonal complex, suggesting that this clonal complex of M. bovis is localized in East Africa. The specific spoligotype pattern of the Af2 clonal complex was rarely identified among isolates from outside Africa, and the few isolates that were found and tested were intact at the RDAf2 locus. We conclude that the Af2 clonal complex is localized to cattle in East Africa. We found that strains of the Af2 clonal complex of M. bovis have, in general, four or more copies of the insertion sequence IS6110, in contrast to the majority of M. bovis strains isolated from cattle, which are thought to carry only one or a few copies. PMID:21097608

  13. Clonal diversity and estimation of relative clone age: application to agrobiodiversity of yam (Dioscorea rotundata)

    PubMed Central

    2013-01-01

    Background Clonal propagation is a particular reproductive system found in both the plant and animal kingdoms, from human parasites to clonally propagated crops. Clonal diversity provides information about plant and animal evolutionary history, i.e. how clones spread, or the age of a particular clone. In plants, this could provide valuable information about agrobiodiversity dynamics and more broadly about the evolutionary history of a particular crop. We studied the evolutionary history of yam, Dioscorea rotundata. In Africa, Yam is cultivated by tuber clonal propagation. Results We used 12 microsatellite markers to identify intra-clonal diversity in yam varieties. We then used this diversity to assess the relative ages of clones. Using simulations, we assessed how Approximate Bayesian Computation could use clonal diversity to estimate the age of a clone depending on the size of the sample, the number of independent samples and the number of markers. We then applied this approach to our particular dataset and showed that the relative ages of varieties could be estimated, and that each variety could be ranked by age. Conclusions We give a first estimation of clone age in an approximate Bayesian framework. However the precise estimation of clone age depends on the precision of the mutation rate. We provide useful information on agrobiodiversity dynamics and suggest recurrent creation of varietal diversity in a clonally propagated crop. PMID:24219837

  14. Strong but diverging clonality - climate relationships of different plant clades explain weak overall pattern across China

    PubMed Central

    Ye, Duo; Liu, Guofang; Song, Yao-Bin; Cornwell, William K.; Dong, Ming; Cornelissen, Johannes H. C.

    2016-01-01

    The clonal strategy should be relatively important in stressful environments (i.e. of low resource availability or harsh climate), e.g. in cold habitats. However, our understanding of the distribution pattern of clonality along environmental gradients is still far from universal. The weakness and inconsistency of overall clonality-climate relationships across taxa, as reported in previous studies, may be due to different phylogenetic lineages having fundamental differences in functional traits other than clonality determining their climate response. Thus, in this study we compared the clonality-climate relationships along a latitudinal gradient within and between different lineages at several taxonomic levels, including four major angiosperm lineages (Magnoliidae, Monocotyledoneae, Superrosidae and Superasteridae), orders and families. To this aim we used a species clonality dataset for 4015 vascular plant species in 545 terrestrial communities across China. Our results revealed clear predictive patterns of clonality proportion in relation to environmental gradients for the predominant representatives of each of the taxonomic levels above, but the relationships differed in shape and strength between the 4 major angiosperm lineages, between the 12 orders and between the 12 families. These different relationships canceled out one another when all lineages at a certain taxonomic level were pooled. Our findings highlight the importance of explicitly accounting for the functional or taxonomic scale for studying variation in plant ecological strategy across environmental gradients. PMID:27246203

  15. Clonal reproduction shapes evolution in the lizard malaria parasite Plasmodium floridense.

    PubMed

    Falk, Bryan G; Glor, Richard E; Perkins, Susan L

    2015-06-01

    The preponderant clonal evolution hypothesis (PCE) predicts that frequent clonal reproduction (sex between two clones) in many pathogens capable of sexual recombination results in strong linkage disequilibrium and the presence of discrete genetic subdivisions characterized by occasional gene flow. We expand on the PCE and predict that higher rates of clonal reproduction will result in: (1) morphologically cryptic species that exhibit (2) low within-species variation and (3) recent between-species divergence. We tested these predictions in the Caribbean lizard malaria parasite Plasmodium floridense using 63 single-infection samples in lizards collected from across the parasite's range, and sequenced them at two mitochondrial, one apicoplast, and five nuclear genes. We identified 11 provisionally cryptic species within P. floridense, each of which exhibits low intraspecific variation and recent divergence times between species (some diverged approximately 110,000 years ago). Our results are consistent with the hypothesis that clonal reproduction can profoundly affect diversification of species capable of sexual recombination, and suggest that clonal reproduction may have led to a large number of unrecognized pathogen species. The factors that may influence the rates of clonal reproduction among pathogens are unclear, and we discuss how prevalence and virulence may relate to clonal reproduction.

  16. Strong but diverging clonality - climate relationships of different plant clades explain weak overall pattern across China

    NASA Astrophysics Data System (ADS)

    Ye, Duo; Liu, Guofang; Song, Yao-Bin; Cornwell, William K.; Dong, Ming; Cornelissen, Johannes H. C.

    2016-06-01

    The clonal strategy should be relatively important in stressful environments (i.e. of low resource availability or harsh climate), e.g. in cold habitats. However, our understanding of the distribution pattern of clonality along environmental gradients is still far from universal. The weakness and inconsistency of overall clonality-climate relationships across taxa, as reported in previous studies, may be due to different phylogenetic lineages having fundamental differences in functional traits other than clonality determining their climate response. Thus, in this study we compared the clonality-climate relationships along a latitudinal gradient within and between different lineages at several taxonomic levels, including four major angiosperm lineages (Magnoliidae, Monocotyledoneae, Superrosidae and Superasteridae), orders and families. To this aim we used a species clonality dataset for 4015 vascular plant species in 545 terrestrial communities across China. Our results revealed clear predictive patterns of clonality proportion in relation to environmental gradients for the predominant representatives of each of the taxonomic levels above, but the relationships differed in shape and strength between the 4 major angiosperm lineages, between the 12 orders and between the 12 families. These different relationships canceled out one another when all lineages at a certain taxonomic level were pooled. Our findings highlight the importance of explicitly accounting for the functional or taxonomic scale for studying variation in plant ecological strategy across environmental gradients.

  17. Clonal Plasticity of Aquatic Plant Species Submitted to Mechanical Stress: Escape versus Resistance Strategy

    PubMed Central

    Puijalon, Sara; Bouma, Tjeerd J.; Van Groenendael, Jan; Bornette, Gudrun

    2008-01-01

    Background and Aims The plastic alterations of clonal architecture are likely to have functional consequences, as they affect the spatial distribution of ramets over patchy environments. However, little is known about the effect of mechanical stresses on the clonal growth. The aim of the present study was to investigate the clonal plasticity induced by mechanical stress consisting of continuous water current encountered by aquatic plants. More particularly, the aim was to test the capacity of the plants to escape this stress through clonal plastic responses. Methods The transplantation of ramets of the same clone in two contrasting flow velocity conditions was carried out for two species (Potamogeton coloratus and Mentha aquatica) which have contrasting clonal growth forms. Relative allocation to clonal growth, to creeping stems in the clonal biomass, number and total length of creeping stems, spacer length and main creeping stem direction were measured. Key Results For P. coloratus, plants exposed to water current displayed increased total length of creeping stems, increased relative allocation to creeping stems within the clonal dry mass and increased spacer length. For M. aquatica, plants exposed to current displayed increased number and total length of creeping stems. Exposure to current induced for both species a significant increase of the proportion of creeping stems in the downstream direction to the detriment of creeping stems perpendicular to flow. Conclusions This study demonstrates that mechanical stress from current flow induced plastic variation in clonal traits for both species. The responses of P. coloratus could lead to an escape strategy, with low benefits with respect to sheltering and anchorage. The responses of M. aquatica that may result in a denser canopy and enhancement of anchorage efficiency could lead to a resistance strategy. PMID:18854376

  18. Parallel programming with PCN

    SciTech Connect

    Foster, I.; Tuecke, S.

    1991-12-01

    PCN is a system for developing and executing parallel programs. It comprises a high-level programming language, tools for developing and debugging programs in this language, and interfaces to Fortran and C that allow the reuse of existing code in multilingual parallel programs. Programs developed using PCN are portable across many different workstations, networks, and parallel computers. This document provides all the information required to develop parallel programs with the PCN programming system. In includes both tutorial and reference material. It also presents the basic concepts that underly PCN, particularly where these are likely to be unfamiliar to the reader, and provides pointers to other documentation on the PCN language, programming techniques, and tools. PCN is in the public domain. The latest version of both the software and this manual can be obtained by anonymous FTP from Argonne National Laboratory in the directory pub/pcn at info.mcs.anl.gov (c.f. Appendix A).

  19. Parallel programming with PCN

    SciTech Connect

    Foster, I.; Tuecke, S.

    1991-09-01

    PCN is a system for developing and executing parallel programs. It comprises a high-level programming language, a set of tools for developing and debugging programs in this language, and interfaces to Fortran and C that allow the reuse of existing code in multilingual parallel programs. Programs developed using PCN are portable across many different workstations, networks, and parallel computers. This document provides all the information required to develop parallel programs with the PCN programming system. It includes both tutorial and reference material. It also presents the basic concepts that underlie PCN, particularly where these are likely to be unfamiliar to the reader, and provides pointers to other documentation on the PCN language, programming techniques, and tools. PCN is in the public domain. The latest version of both the software and this manual can be obtained by anonymous FTP from Argonne National Laboratory at info.mcs.anl.gov.

  20. The Parallel Axiom

    ERIC Educational Resources Information Center

    Rogers, Pat

    1972-01-01

    Criteria for a reasonable axiomatic system are discussed. A discussion of the historical attempts to prove the independence of Euclids parallel postulate introduces non-Euclidean geometries. Poincare's model for a non-Euclidean geometry is defined and analyzed. (LS)

  1. Scalable parallel communications

    NASA Technical Reports Server (NTRS)

    Maly, K.; Khanna, S.; Overstreet, C. M.; Mukkamala, R.; Zubair, M.; Sekhar, Y. S.; Foudriat, E. C.

    1992-01-01

    Coarse-grain parallelism in networking (that is, the use of multiple protocol processors running replicated software sending over several physical channels) can be used to provide gigabit communications for a single application. Since parallel network performance is highly dependent on real issues such as hardware properties (e.g., memory speeds and cache hit rates), operating system overhead (e.g., interrupt handling), and protocol performance (e.g., effect of timeouts), we have performed detailed simulations studies of both a bus-based multiprocessor workstation node (based on the Sun Galaxy MP multiprocessor) and a distributed-memory parallel computer node (based on the Touchstone DELTA) to evaluate the behavior of coarse-grain parallelism. Our results indicate: (1) coarse-grain parallelism can deliver multiple 100 Mbps with currently available hardware platforms and existing networking protocols (such as Transmission Control Protocol/Internet Protocol (TCP/IP) and parallel Fiber Distributed Data Interface (FDDI) rings); (2) scale-up is near linear in n, the number of protocol processors, and channels (for small n and up to a few hundred Mbps); and (3) since these results are based on existing hardware without specialized devices (except perhaps for some simple modifications of the FDDI boards), this is a low cost solution to providing multiple 100 Mbps on current machines. In addition, from both the performance analysis and the properties of these architectures, we conclude: (1) multiple processors providing identical services and the use of space division multiplexing for the physical channels can provide better reliability than monolithic approaches (it also provides graceful degradation and low-cost load balancing); (2) coarse-grain parallelism supports running several transport protocols in parallel to provide different types of service (for example, one TCP handles small messages for many users, other TCP's running in parallel provide high bandwidth

  2. Parallel image compression

    NASA Technical Reports Server (NTRS)

    Reif, John H.

    1987-01-01

    A parallel compression algorithm for the 16,384 processor MPP machine was developed. The serial version of the algorithm can be viewed as a combination of on-line dynamic lossless test compression techniques (which employ simple learning strategies) and vector quantization. These concepts are described. How these concepts are combined to form a new strategy for performing dynamic on-line lossy compression is discussed. Finally, the implementation of this algorithm in a massively parallel fashion on the MPP is discussed.

  3. Revisiting and parallelizing SHAKE

    NASA Astrophysics Data System (ADS)

    Weinbach, Yael; Elber, Ron

    2005-10-01

    An algorithm is presented for running SHAKE in parallel. SHAKE is a widely used approach to compute molecular dynamics trajectories with constraints. An essential step in SHAKE is the solution of a sparse linear problem of the type Ax = b, where x is a vector of unknowns. Conjugate gradient minimization (that can be done in parallel) replaces the widely used iteration process that is inherently serial. Numerical examples present good load balancing and are limited only by communication time.

  4. Microsatellites within the feline androgen receptor are suitable for X chromosome-linked clonality testing in archival material.

    PubMed

    Farwick, Nadine M; Klopfleisch, Robert; Gruber, Achim D; Weiss, Alexander Th A

    2017-04-01

    Objectives A hallmark of neoplasms is their origin from a single cell; that is, clonality. Many techniques have been developed in human medicine to utilise this feature of tumours for diagnostic purposes. One approach is X chromosome-linked clonality testing using polymorphisms of genes encoded by genes on the X chromosome. The aim of this study was to determine if the feline androgen receptor gene was suitable for X chromosome-linked clonality testing. Methods The feline androgen receptor gene was characterised and used to test clonality of feline lymphomas by PCR and polyacrylamide gel electrophoresis, using archival formalin-fixed, paraffin-embedded material. Results Clonality of the feline lymphomas under study was confirmed and the gene locus was shown to represent a suitable target in clonality testing. Conclusions and relevance Because there are some pitfalls of using X chromosome-linked clonality testing, further studies are necessary to establish this technique in the cat.

  5. Clonal relationships among bloodstream isolates of Escherichia coli.

    PubMed

    Maslow, J N; Whittam, T S; Gilks, C F; Wilson, R A; Mulligan, M E; Adams, K S; Arbeit, R D

    1995-07-01

    The clonal relationships among 187 bloodstream isolates of Escherichia coli from 179 patients at Boston, Mass., Long Beach, Calif., and Nairobi, Kenya, were determined by multilocus enzyme electrophoresis (MLEE), analysis of polymorphisms associated with the ribosomal operon (ribotyping), and serotyping. MLEE based on 20 enzymes resolved 101 electrophoretic types (ETs), forming five clusters; ribotyping resolved 56 distinct patterns concordant with the analysis by MLEE. The isolates at each study site formed a genetically diverse group and demonstrated similar clonal structures, with the same small subset of lineages accounting for the majority of isolates at each site. Moreover, two ribotypes accounted for approximately 30% of the isolates at each study site. One cluster contained the majority (65%) of isolates and, by direct comparison of the ETs and ribotypes of individual isolates, was genetically indistinguishable from the largest cluster for each of two other collections of E. coli causing pyelonephritis and neonatal meningitis (R. K. Selander, T. K. Korhonen, V. Väisänen-Rhen, P. H. Williams, P. E. Pattison, and D. A. Caugent, Infect. Immun. 52:213-222, 1986; M. Arthur, C. E. Johnson, R. H. Rubin, R. D. Arbeit, C. Campanelli, C. Kim, S. Steinbach, M. Agarwal, R. Wilkinson, and R. Goldstein, Infect. Immun. 57:303-313, 1989), thus defining a virulent set of lineages. The isolates within these virulent lineages typically carried DNA homologous to the adhesin operon pap or sfa and the hemolysin operon hly and expressed O1, O2, O4, O6, O18, O25, or O75 antigens. DNA homologous to pap was distributed among isolates of each major cluster, whereas hly was restricted to isolates of two clusters, typically detected in pap-positive strains, and sfa was restricted to isolates of one cluster, typically detected in pap- and hly-positive strains. The occurrence of pap-positive isolates in the same geographically and genetically divergent lineages suggests that this

  6. Epigenetic Memory as a Basis for Intelligent Behavior in Clonal Plants

    PubMed Central

    Latzel, Vít; Rendina González, Alejandra P.; Rosenthal, Jonathan

    2016-01-01

    Environmentally induced epigenetic change enables plants to remember past environmental interactions. If this memory capability is exploited to prepare plants for future challenges, it can provide a basis for highly sophisticated behavior, considered intelligent by some. Against the backdrop of an overview of plant intelligence, we hypothesize: (1) that the capability of plants to engage in such intelligent behavior increases with the additional level of complexity afforded by clonality, and; (2) that more faithful inheritance of epigenetic information in clonal plants, in conjunction with information exchange and coordination between connected ramets, is likely to enable especially advanced intelligent behavior in this group. We therefore further hypothesize that this behavior provides ecological and evolutionary advantages to clonal plants, possibly explaining, at least in part, their widespread success. Finally, we suggest avenues of inquiry to enable assessing intelligent behavior and the role of epigenetic memory in clonal species. PMID:27630664

  7. Clonality in myeloproliferative disorders: Analysis by means of polymerase chain reaction

    SciTech Connect

    Gilliland, D.G.; Blanchard, K.L.; Levy, J.; Perrin, S.; Bunn, H.F. )

    1991-08-01

    The myeloproliferative syndromes are acquired disorders of hematopoiesis that provide insights into the transition from somatic cell mutation to neoplasia. The clonal origin of specific blood cells can be assessed in patients with X chromosome-linked polymorphisms, taking advantage of random inactivation of the X chromosome. The authors have adapted the PCR for determination of clonality on as few as 100 cells, including individual colonies grown in culture. Amplifying a polymorphic portion of the X chromosome-linked phosphoglycerate kinase (PGK) gene after selective digestion of the active X chromosome with a methylation-sensitive restriction enzyme gave results fully concordant with standard Southern blotting of DNA samples form normal (polyclonal) polymorphonuclear cells (PMN) as well as clonal PMN from patients with myelodysplastic syndrome and polycythemia vera (PCV). They have used this technique to demonstrate heterogeneity of lineage involvement in patients with PCV. The same clinical phenotype may arise from clonal proliferation of different hematopoietic progenitors.

  8. Epigenetic Memory as a Basis for Intelligent Behavior in Clonal Plants.

    PubMed

    Latzel, Vít; Rendina González, Alejandra P; Rosenthal, Jonathan

    2016-01-01

    Environmentally induced epigenetic change enables plants to remember past environmental interactions. If this memory capability is exploited to prepare plants for future challenges, it can provide a basis for highly sophisticated behavior, considered intelligent by some. Against the backdrop of an overview of plant intelligence, we hypothesize: (1) that the capability of plants to engage in such intelligent behavior increases with the additional level of complexity afforded by clonality, and; (2) that more faithful inheritance of epigenetic information in clonal plants, in conjunction with information exchange and coordination between connected ramets, is likely to enable especially advanced intelligent behavior in this group. We therefore further hypothesize that this behavior provides ecological and evolutionary advantages to clonal plants, possibly explaining, at least in part, their widespread success. Finally, we suggest avenues of inquiry to enable assessing intelligent behavior and the role of epigenetic memory in clonal species.

  9. Novel R tools for analysis of genome-wide population genetic data with emphasis on clonality

    PubMed Central

    Kamvar, Zhian N.; Brooks, Jonah C.; Grünwald, Niklaus J.

    2015-01-01

    To gain a detailed understanding of how plant microbes evolve and adapt to hosts, pesticides, and other factors, knowledge of the population dynamics and evolutionary history of populations is crucial. Plant pathogen populations are often clonal or partially clonal which requires different analytical tools. With the advent of high throughput sequencing technologies, obtaining genome-wide population genetic data has become easier than ever before. We previously contributed the R package poppr specifically addressing issues with analysis of clonal populations. In this paper we provide several significant extensions to poppr with a focus on large, genome-wide SNP data. Specifically, we provide several new functionalities including the new function mlg.filter to define clone boundaries allowing for inspection and definition of what is a clonal lineage, minimum spanning networks with reticulation, a sliding-window analysis of the index of association, modular bootstrapping of any genetic distance, and analyses across any level of hierarchies. PMID:26113860

  10. T-cell stimuli independently sum to regulate an inherited clonal division fate

    PubMed Central

    Marchingo, J. M.; Prevedello, G.; Kan, A.; Heinzel, S.; Hodgkin, P. D.; Duffy, K. R.

    2016-01-01

    In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates. Progeny from clonal families cease dividing in the same or adjacent generations, with inter-clonal variation producing burst-size diversity. The effects of costimulatory signals on individual clones sum together with stochastic independence; therefore, the net effect across multiple clones produces consistent, but heterogeneous population responses. These data demonstrate that substantial clonal heterogeneity arises through differences in experience of clonal progenitors, either through stochastic antigen interaction or by differences in initial receptor sensitivities. PMID:27869196

  11. Detectable clonal mosaicism from birth to old age and its relationship to cancer.

    PubMed

    Laurie, Cathy C; Laurie, Cecelia A; Rice, Kenneth; Doheny, Kimberly F; Zelnick, Leila R; McHugh, Caitlin P; Ling, Hua; Hetrick, Kurt N; Pugh, Elizabeth W; Amos, Chris; Wei, Qingyi; Wang, Li-e; Lee, Jeffrey E; Barnes, Kathleen C; Hansel, Nadia N; Mathias, Rasika; Daley, Denise; Beaty, Terri H; Scott, Alan F; Ruczinski, Ingo; Scharpf, Rob B; Bierut, Laura J; Hartz, Sarah M; Landi, Maria Teresa; Freedman, Neal D; Goldin, Lynn R; Ginsburg, David; Li, Jun; Desch, Karl C; Strom, Sara S; Blot, William J; Signorello, Lisa B; Ingles, Sue A; Chanock, Stephen J; Berndt, Sonja I; Le Marchand, Loic; Henderson, Brian E; Monroe, Kristine R; Heit, John A; de Andrade, Mariza; Armasu, Sebastian M; Regnier, Cynthia; Lowe, William L; Hayes, M Geoffrey; Marazita, Mary L; Feingold, Eleanor; Murray, Jeffrey C; Melbye, Mads; Feenstra, Bjarke; Kang, Jae H; Wiggs, Janey L; Jarvik, Gail P; McDavid, Andrew N; Seshan, Venkatraman E; Mirel, Daniel B; Crenshaw, Andrew; Sharopova, Nataliya; Wise, Anastasia; Shen, Jess; Crosslin, David R; Levine, David M; Zheng, Xiuwen; Udren, Jenna I; Bennett, Siiri; Nelson, Sarah C; Gogarten, Stephanie M; Conomos, Matthew P; Heagerty, Patrick; Manolio, Teri; Pasquale, Louis R; Haiman, Christopher A; Caporaso, Neil; Weir, Bruce S

    2012-05-06

    We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

  12. Temporal dynamics of genotypic diversity reveal strong clonal selection in the aphid Myzus persicae.

    PubMed

    Vorburger, C

    2006-01-01

    Parthenogenetic organisms often harbour substantial genotypic diversity. This diversity may be the result of recurrent formations of new clones, or it may be maintained by environmental heterogeneity acting on ecological differences among clones. In aphids, both processes may be important because obligate and cyclical parthenogens can form mixed populations. Using microsatellites, I analysed the temporal dynamics of clonal diversity in such a population of the aphid Myzus persicae over a 1-year period. The frequency distribution of clonal genotypes was very skewed, with many rare and few common clones. The relative frequencies of common clones underwent strong and rapid changes indicative of intense clonal selection. Differences in their host associations suggest that these shifts may partly be caused by changes in the abundance of annual host plants. Other selective factors of potential importance are also discussed. New, sexually produced genotypes made a minor contribution to clonal diversity, consistent with the observed heterozygote excess characteristic of predominantly asexual populations in M. persicae.

  13. Parallel architectures for vision

    SciTech Connect

    Maresca, M. ); Lavin, M.A. ); Li, H. )

    1988-08-01

    Vision computing involves the execution of a large number of operations on large sets of structured data. Sequential computers cannot achieve the speed required by most of the current applications and therefore parallel architectural solutions have to be explored. In this paper the authors examine the options that drive the design of a vision oriented computer, starting with the analysis of the basic vision computation and communication requirements. They briefly review the classical taxonomy for parallel computers, based on the multiplicity of the instruction and data stream, and apply a recently proposed criterion, the degree of autonomy of each processor, to further classify fine-grain SIMD massively parallel computers. They identify three types of processor autonomy, namely operation autonomy, addressing autonomy, and connection autonomy. For each type they give the basic definitions and show some examples. They focus on the concept of connection autonomy, which they believe is a key point in the development of massively parallel architectures for vision. They show two examples of parallel computers featuring different types of connection autonomy - the Connection Machine and the Polymorphic-Torus - and compare their cost and benefit.

  14. Sublattice parallel replica dynamics

    NASA Astrophysics Data System (ADS)

    Martínez, Enrique; Uberuaga, Blas P.; Voter, Arthur F.

    2014-06-01

    Exascale computing presents a challenge for the scientific community as new algorithms must be developed to take full advantage of the new computing paradigm. Atomistic simulation methods that offer full fidelity to the underlying potential, i.e., molecular dynamics (MD) and parallel replica dynamics, fail to use the whole machine speedup, leaving a region in time and sample size space that is unattainable with current algorithms. In this paper, we present an extension of the parallel replica dynamics algorithm [A. F. Voter, Phys. Rev. B 57, R13985 (1998), 10.1103/PhysRevB.57.R13985] by combining it with the synchronous sublattice approach of Shim and Amar [Y. Shim and J. G. Amar, Phys. Rev. B 71, 125432 (2005), 10.1103/PhysRevB.71.125432], thereby exploiting event locality to improve the algorithm scalability. This algorithm is based on a domain decomposition in which events happen independently in different regions in the sample. We develop an analytical expression for the speedup given by this sublattice parallel replica dynamics algorithm and compare it with parallel MD and traditional parallel replica dynamics. We demonstrate how this algorithm, which introduces a slight additional approximation of event locality, enables the study of physical systems unreachable with traditional methodologies and promises to better utilize the resources of current high performance and future exascale computers.

  15. Clonal dominance among T-lymphocyte infiltrates in arthritis

    SciTech Connect

    Stamenkovic, I.; Stegagno, M.; Wright, K.A.; Krane, S.M.; Amento, E.P.; Colvin, R.B.; Duquesnoy, R.J.; Kurnick, J.T.

    1988-02-01

    Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) ..beta..-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders.

  16. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    SciTech Connect

    Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun; Juhn, Kyoung-Mi; Woo, Seon Rang; Kim, Hee-Young; Han, Young-Hoon; Hwang, Sang-Gu; Hong, Sung-Hee; Kang, Chang-Mo; Yoo, Young-Do; Park, Won-Bong; Cho, Myung-Haing; Park, Gil Hong; Lee, Kee-Ho

    2010-11-12

    Research highlights: {yields} In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. {yields} The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. {yields} The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. {yields} P53 status is not associated with the occurrence of unsensitized clone. {yields} Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC{sup -/-} cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC{sup -/-} clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  17. Breast Cancer Brain Metastases: Clonal Evolution in Clinical Context

    PubMed Central

    Saunus, Jodi M.; McCart Reed, Amy E.; Lim, Zhun Leong; Lakhani, Sunil R.

    2017-01-01

    Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management. PMID:28098771

  18. T cell fate and clonality inference from single cell transcriptomes

    PubMed Central

    Proserpio, Valentina; Clare, Simon; Speak, Anneliese O.; Dougan, Gordon; Teichmann, Sarah A.

    2016-01-01

    The enormous sequence diversity within T cell receptor (TCR) repertoires allows specific TCR sequences to be used as lineage markers for T cells that derive from a common progenitor. We have developed a computational method, called TraCeR, to reconstruct full-length, paired TCR sequences from T lymphocyte single-cell RNA-seq by combining existing assembly and alignment programs with “combinatorial recombinome” sequences comprising all possible TCR combinations. We validate this method to quantify its accuracy and sensitivity. Inferred TCR sequences reveal clonal relationships between T cells whilst the cells’ complete transcriptional landscapes can be quantified from the remaining RNA-seq data. This provides a powerful tool to link T cell specificity with functional response and we demonstrate this by determining the distribution of members of expanded T cell clonotypes in a mouse Salmonella infection model. Members of the same clonotype span early activated CD4+ T cells, as well as mature effector and memory cells. PMID:26950746

  19. Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution.

    PubMed

    Bozic, Ivana; Gerold, Jeffrey M; Nowak, Martin A

    2016-02-01

    The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion.

  20. Plasmid and clonal interference during post horizontal gene transfer evolution.

    PubMed

    Bedhomme, S; Perez Pantoja, D; Bravo, I G

    2017-02-16

    Plasmids are nucleic acid molecules that can drive their own replication in a living cell. They can be transmitted horizontally and can thrive in the host cell to high-copy numbers. Plasmid replication and gene expression consume cellular resources and cells carrying plasmids incur fitness costs. But many plasmids carry genes that can be beneficial under certain conditions, allowing the cell to endure in the presence of antibiotics, toxins, competitors or parasites. Horizontal transfer of plasmid-encoded genes can thus instantaneously confer differential adaptation to local or transient selection conditions. This conflict between cellular fitness and plasmid spread sets the scene for multilevel selection processes. We have engineered a system to study the short-term evolutionary impact of different synonymous versions of a plasmid-encoded antibiotic resistance gene. Applying experimental evolution under different selection conditions and deep sequencing allowed us to show rapid local adaptation to the presence of antibiotic and to the specific version of the resistance gene transferred. We describe the presence of clonal interference at two different levels: at the within-cell level, because a single cell can carry several plasmids, and at the between-cell level, because a bacterial population may contain several clones carrying different plasmids and displaying different fitness in the presence/absence of antibiotic. Understanding the within-cell and between-cell dynamics of plasmids after horizontal gene transfer is essential to unravel the dense network of mobile elements underlying the worldwide threat to public health of antibiotic resistance.

  1. Decoding astrocyte heterogeneity: New tools for clonal analysis.

    PubMed

    Bribián, A; Figueres-Oñate, M; Martín-López, E; López-Mascaraque, L

    2016-05-26

    The importance of astrocyte heterogeneity came out as a hot topic in neurosciences especially over the last decades, when the development of new methodologies allowed demonstrating the existence of big differences in morphological, neurochemical and physiological features between astrocytes. However, although the knowledge about the biology of astrocytes is increasing rapidly, an important characteristic that remained unexplored, until the last years, has been the relationship between astrocyte lineages and cell heterogeneity. To fill this gap, a new method called StarTrack was recently developed, a powerful genetic tool that allows tracking astrocyte lineages forming cell clones. Using StarTrack, a single astrocyte progenitor and its progeny can be specifically labeled from its generation, during embryonic development, to its final fate in the adult brain. Because of this specific labeling, astrocyte clones, exhibiting heterogeneous morphologies and features, can be easily analyzed in relation to their ontogenetic origin. This review summarizes how astrocyte heterogeneity can be decoded studying the embryonic development of astrocyte lineages and their clonal relationship. Finally, we discuss about some of the challenges and opportunities emerging in this exciting area of investigation.

  2. Clonal competition with alternating dominance in multiple myeloma

    PubMed Central

    Keats, Jonathan J.; Chesi, Marta; Egan, Jan B.; Garbitt, Victoria M.; Palmer, Stephen E.; Braggio, Esteban; Van Wier, Scott; Blackburn, Patrick R.; Baker, Angela S.; Dispenzieri, Angela; Kumar, Shaji; Rajkumar, S. Vincent; Carpten, John D.; Barrett, Michael; Fonseca, Rafael; Stewart, A. Keith

    2012-01-01

    Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few changes over time, whereas those of cytogenetically high-risk patients show significantly more changes over time. The results indicate the existence of 3 temporal tumor types, which can either be genetically stable, linearly evolving, or heterogeneous clonal mixtures with shifting predominant clones. A detailed analysis of one high-risk patient sampled at 7 time points over the entire disease course identified 2 competing subclones that alternate in a back and forth manner for dominance with therapy until one clone underwent a dramatic linear evolution. With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection. PMID:22498740

  3. Adapting clinical paradigms to the challenges of cancer clonal evolution.

    PubMed

    Murugaesu, Nirupa; Chew, Su Kit; Swanton, Charles

    2013-06-01

    Emerging evidence suggests that cancer branched evolution may affect biomarker validation, clinical outcome, and emergence of drug resistance. The changing spatial and temporal nature of cancer subclonal architecture during the disease course suggests the need for longitudinal prospective studies of cancer evolution and robust and clinically implementable pathologic definitions of intratumor heterogeneity, genetic diversity, and chromosomal instability. Furthermore, subclonal heterogeneous events in tumors may evade detection through conventional biomarker strategies and influence clinical outcome. Minimally invasive methods for the study of cancer evolution and new approaches to clinical study design, incorporating understanding of the dynamics of tumor clonal architectures through treatment and during acquisition of drug resistance, have been suggested as important areas for development. Coordinated efforts will be required by the scientific and clinical trial communities to adapt to the challenges of detecting infrequently occurring somatic events that may influence clinical outcome and to understand the dynamics of cancer evolution and the waxing and waning of tumor subclones over time in advanced metastatic epithelial malignancies.

  4. Detectable clonal mosaicism and its relationship to aging and cancer

    PubMed Central

    Jacobs, Kevin B; Yeager, Meredith; Zhou, Weiyin; Wacholder, Sholom; Wang, Zhaoming; Rodriguez-Santiago, Benjamin; Hutchinson, Amy; Deng, Xiang; Liu, Chenwei; Horner, Marie-Josephe; Cullen, Michael; Epstein, Caroline G; Burdett, Laurie; Dean, Michael C; Chatterjee, Nilanjan; Sampson, Joshua; Chung, Charles C; Kovaks, Joseph; Gapstur, Susan M; Stevens, Victoria L; Teras, Lauren T; Gaudet, Mia M; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Taylor, Philip R; Freedman, Neal D; Abnet, Christian C; Goldstein, Alisa M; Hu, Nan; Yu, Kai; Yuan, Jian-Min; Liao, Linda; Ding, Ti; Qiao, You-Lin; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Aldrich, Melinda C; Amos, Christopher; Blot, William J; Bock, Cathryn H; Gillanders, Elizabeth M; Harris, Curtis C; Haiman, Christopher A; Henderson, Brian E; Kolonel, Laurence N; Le Marchand, Loic; McNeill, Lorna H; Rybicki, Benjamin A; Schwartz, Ann G; Signorello, Lisa B; Spitz, Margaret R; Wiencke, John K; Wrensch, Margaret; Wu, Xifeng; Zanetti, Krista A; Ziegler, Regina G; Figueroa, Jonine D; Garcia-Closas, Montserrat; Malats, Nuria; Marenne, Gaelle; Prokunina-Olsson, Ludmila; Baris, Dalsu; Schwenn, Molly; Johnson, Alison; Landi, Maria Teresa; Goldin, Lynn; Consonni, Dario; Bertazzi, Pier Alberto; Rotunno, Melissa; Rajaraman, Preetha; Andersson, Ulrika; Freeman, Laura E Beane; Berg, Christine D; Buring, Julie E; Butler, Mary A; Carreon, Tania; Feychting, Maria; Ahlbom, Anders; Gaziano, J Michael; Giles, Graham G; Hallmans, Goran; Hankinson, Susan E; Hartge, Patricia; Henriksson, Roger; Inskip, Peter D; Johansen, Christoffer; Landgren, Annelie; McKean-Cowdin, Roberta; Michaud, Dominique S; Melin, Beatrice S; Peters, Ulrike; Ruder, Avima M; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Silverman, Debra T; Kogevinas, Manolis; Gonzalez, Juan R; Villa, Olaya; Li, Donghui; Duell, Eric J; Risch, Harvey A; Olson, Sara H; Kooperberg, Charles; Wolpin, Brian M; Jiao, Li; Hassan, Manal; Wheeler, William; Arslan, Alan A; Bas Bueno-de-Mesquita, H; Fuchs, Charles S; Gallinger, Steven; Gross, Myron D; Holly, Elizabeth A; Klein, Alison P; LaCroix, Andrea; Mandelson, Margaret T; Petersen, Gloria; Boutron-Ruault, Marie-Christine; Bracci, Paige M; Canzian, Federico; Chang, Kenneth; Cotterchio, Michelle; Giovannucci, Edward L; Goggins, Michael; Bolton, Judith A Hoffman; Jenab, Mazda; Khaw, Kay-Tee; Krogh, Vittorio; Kurtz, Robert C; McWilliams, Robert R; Mendelsohn, Julie B; Rabe, Kari G; Riboli, Elio; Tjønneland, Anne; Tobias, Geoffrey S; Trichopoulos, Dimitrios; Elena, Joanne W; Yu, Herbert; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael Z; Kraft, Peter; Schumacher, Fredrick; Stram, Daniel; Savage, Sharon A; Mirabello, Lisa; Andrulis, Irene L; Wunder, Jay S; García, Ana Patiño; Sierrasesúmaga, Luis; Barkauskas, Donald A; Gorlick, Richard G; Purdue, Mark; Chow, Wong-Ho; Moore, Lee E; Schwartz, Kendra L; Davis, Faith G; Hsing, Ann W; Berndt, Sonja I; Black, Amanda; Wentzensen, Nicolas; Brinton, Louise A; Lissowska, Jolanta; Peplonska, Beata; McGlynn, Katherine A; Cook, Michael B; Graubard, Barry I; Kratz, Christian P; Greene, Mark H; Erickson, Ralph L; Hunter, David J; Thomas, Gilles; Hoover, Robert N; Real, Francisco X; Fraumeni, Joseph F; Caporaso, Neil E; Tucker, Margaret; Rothman, Nathaniel; Pérez-Jurado, Luis A; Chanock, Stephen J

    2012-01-01

    In an analysis of 31,717 cancer cases and 26,136 cancer-free controls drawn from 13 genome-wide association studies (GWAS), we observed large chromosomal abnormalities in a subset of clones from DNA obtained from blood or buccal samples. Mosaic chromosomal abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of size >2 Mb were observed in autosomes of 517 individuals (0.89%) with abnormal cell proportions between 7% and 95%. In cancer-free individuals, the frequency increased with age; 0.23% under 50 and 1.91% between 75 and 79 (p=4.8×10−8). Mosaic abnormalities were more frequent in individuals with solid-tumors (0.97% versus 0.74% in cancer-free individuals, OR=1.25, p=0.016), with a stronger association for cases who had DNA collected prior to diagnosis or treatment (OR=1.45, p=0.0005). Detectable clonal mosaicism was common in individuals for whom DNA was collected at least one year prior to diagnosis of leukemia compared to cancer-free individuals (OR=35.4, p=3.8×10−11). These findings underscore the importance of the role and time-dependent nature of somatic events in the etiology of cancer and other late-onset diseases. PMID:22561519

  5. Bacterial diversity of symptomatic primary endodontic infection by clonal analysis.

    PubMed

    Nóbrega, Letícia Maria Menezes; Montagner, Francisco; Ribeiro, Adriana Costa; Mayer, Márcia Alves Pinto; Gomes, Brenda Paula Figueiredo de Almeida

    2016-10-10

    The aim of this study was to explore the bacterial diversity of 10 root canals with acute apical abscess using clonal analysis. Samples were collected from 10 patients and submitted to bacterial DNA isolation, 16S rRNA gene amplification, cloning, and sequencing. A bacterial genomic library was constructed and bacterial diversity was estimated. The mean number of taxa per canal was 15, ranging from 11 to 21. A total of 689 clones were analyzed and 76 phylotypes identified, of which 47 (61.84%) were different species and 29 (38.15%) were taxa reported as yet-uncultivable or as yet-uncharacterized species. Prevotella spp., Fusobacterium nucleatum, Filifactor alocis, and Peptostreptococcus stomatis were the most frequently detected species, followed by Dialister invisus, Phocaeicola abscessus, the uncharacterized Lachnospiraceae oral clone, Porphyromonas spp., and Parvimonas micra. Eight phyla were detected and the most frequently identified taxa belonged to the phylum Firmicutes (43.5%), followed by Bacteroidetes (22.5%) and Proteobacteria (13.2%). No species was detected in all studied samples and some species were identified in only one case. It was concluded that acute primary endodontic infection is characterized by wide bacterial diversity and a high intersubject variability was observed. Anaerobic Gram-negative bacteria belonging to the phylum Firmicutes, followed by Bacteroidetes, were the most frequently detected microorganisms.

  6. Emerging sporotrichosis is driven by clonal and recombinant Sporothrix species

    PubMed Central

    Rodrigues, Anderson Messias; de Hoog, GSybren; Zhang, Yu; de Camargo, Zoilo Pires

    2014-01-01

    Sporotrichosis, caused by agents of the fungal genus Sporothrix, occurs worldwide, but the infectious species are not evenly distributed. Sporothrix propagules usually gain entry into the warm-blooded host through minor trauma to the skin from contaminated plant debris or through scratches or bites from felines carrying the disease, generally in the form of outbreaks. Over the last decade, sporotrichosis has changed from a relatively obscure endemic infection to an epidemic zoonotic health problem. We evaluated the impact of the feline host on the epidemiology, spatial distribution, prevalence and genetic diversity of human sporotrichosis. Nuclear and mitochondrial markers revealed large structural genetic differences between S. brasiliensis and S. schenckii populations, suggesting that the interplay of host, pathogen and environment has a structuring effect on the diversity, frequency and distribution of Sporothrix species. Phylogenetic data support a recent habitat shift within S. brasiliensis from plant to cat that seems to have occurred in southeastern Brazil and is responsible for its emergence. A clonal structure was found in the early expansionary phase of the cat–human epidemic. However, the prevalent recombination structure in the plant-associated pathogen S. schenckii generates a diversity of genotypes that did not show any significant increase in frequency as etiological agents of human infection over time. These results suggest that closely related pathogens can follow different strategies in epidemics. Thus, species-specific types of transmission may require distinct public health strategies for disease control. PMID:26038739

  7. Plastic reproductive strategies in a clonal marine invertebrate.

    PubMed Central

    McGovern, Tamara M

    2003-01-01

    Plastic reproductive allocation may allow individuals to maximize their fitness when conditions vary. Mate availability is one condition that may determine the fitness of an individual's allocation strategy. Using a variety of methods, I detected evidence of plastic allocation to asexual (clonal) reproduction in response to mate availability in the brittle star Ophiactis savignyi. There were more mature individuals in populations in which both sexes were present, and clones from these populations had fewer clone-mates than clones from single-sex populations. Animals placed with mates in a field experiment divided less frequently than animals without a mate. These findings demonstrate that animals reduce their allocation to asexual reproduction when mates are present and when a loss of fecundity associated with cloning would decrease offspring production. This plasticity is probably adaptive because it maximizes sexual-reproductive potential when fertilization is more likely, but maximizes survival of the clone when mates are absent and gametes are unlikely to be converted to offspring. PMID:14667344

  8. Adapting populations in space: clonal interference and genetic diversity

    NASA Astrophysics Data System (ADS)

    Weissman, Daniel; Barton, Nick

    Most species inhabit ranges much larger than the scales over which individuals interact. How does this spatial structure interact with adaptive evolution? We consider a simple model of a spatially-extended, adapting population and show that, while clonal interference severely limits the adaptation of purely asexual populations, even rare recombination is enough to allow adaptation at rates approaching those of well-mixed populations. We also find that the genetic hitchhiking produced by the adaptive alleles sweeping through the population has strange effects on the patterns of genetic diversity. In large spatial ranges, even low rates of adaptation cause all individuals in the population to rapidly trace their ancestry back to individuals living in a small region in the center of the range. The probability of fixation of an allele is thus strongly dependent on the allele's spatial location, with alleles from the center favored. Surprisingly, these effects are seen genome-wide (instead of being localized to the regions of the genome undergoing the sweeps). The spatial concentration of ancestry produces a power-law dependence of relatedness on distance, so that even individuals sampled far apart are likely to be fairly closely related, masking the underlying spatial structure.

  9. Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution

    PubMed Central

    Bozic, Ivana; Gerold, Jeffrey M.; Nowak, Martin A.

    2016-01-01

    The vast majority of mutations in the exome of cancer cells are passengers, which do not affect the reproductive rate of the cell. Passengers can provide important information about the evolutionary history of an individual cancer, and serve as a molecular clock. Passengers can also become targets for immunotherapy or confer resistance to treatment. We study the stochastic expansion of a population of cancer cells describing the growth of primary tumors or metastatic lesions. We first analyze the process by looking forward in time and calculate the fixation probabilities and frequencies of successive passenger mutations ordered by their time of appearance. We compute the likelihood of specific evolutionary trees, thereby informing the phylogenetic reconstruction of cancer evolution in individual patients. Next, we derive results looking backward in time: for a given subclonal mutation we estimate the number of cancer cells that were present at the time when that mutation arose. We derive exact formulas for the expected numbers of subclonal mutations of any frequency. Fitting this formula to cancer sequencing data leads to an estimate for the ratio of birth and death rates of cancer cells during the early stages of clonal expansion. PMID:26828429

  10. Longevity of clonal plants: why it matters and how to measure it

    PubMed Central

    de Witte, Lucienne C.; Stöcklin, Jürg

    2010-01-01

    Background Species' life-history and population dynamics are strongly shaped by the longevity of individuals, but life span is one of the least accessible demographic traits, particularly in clonal plants. Continuous vegetative reproduction of genets enables persistence despite low or no sexual reproduction, affecting genet turnover rates and population stability. Therefore, the longevity of clonal plants is of considerable biological interest, but remains relatively poorly known. Scope Here, we critically review the present knowledge on the longevity of clonal plants and discuss its importance for population persistence. Direct life-span measurements such as growth-ring analysis in woody plants are relatively easy to take, although, for many clonal plants, these methods are not adequate due to the variable growth pattern of ramets and difficult genet identification. Recently, indirect methods have been introduced in which genet size and annual shoot increments are used to estimate genet age. These methods, often based on molecular techniques, allow the investigation of genet size and age structure of whole populations, a crucial issue for understanding their viability and persistence. However, indirect estimates of clonal longevity are impeded because the process of ageing in clonal plants is still poorly understood and because their size and age are not always well correlated. Alternative estimators for genet life span such as somatic mutations have recently been suggested. Conclusions Empirical knowledge on the longevity of clonal species has increased considerably in the last few years. Maximum age estimates are an indicator of population persistence, but are not sufficient to evaluate turnover rates and the ability of long-lived clonal plants to enhance community stability and ecosystem resilience. In order to understand the dynamics of populations it will be necessary to measure genet size and age structure, not only life spans of single individuals, and to

  11. Differential Influence of Clonal Integration on Morphological and Growth Responses to Light in Two Invasive Herbs

    PubMed Central

    Xu, Cheng-Yuan; Schooler, Shon S.; Van Klinken, Rieks D.

    2012-01-01

    Background and aims In contrast to seeds, high sensitivity of vegetative fragments to unfavourable environments may limit the expansion of clonal invasive plants. However, clonal integration promotes the establishment of propagules in less suitable habitats and may facilitate the expansion of clonal invaders into intact native communities. Here, we examine the influence of clonal integration on the morphology and growth of ramets in two invasive plants, Alternanthera philoxeroides and Phyla canescens, under varying light conditions. Methods In a greenhouse experiment, branches, connected ramets and severed ramets of the same mother plant were exposed under full sun and 85% shade and their morphological and growth responses were assessed. Key results The influence of clonal integration on the light reaction norm (connection×light interaction) of daughter ramets was species-specific. For A. philoxeroides, clonal integration evened out the light response (total biomass, leaf mass per area, and stem number, diameter and length) displayed in severed ramets, but these connection×light interactions were largely absent for P. canescens. Nevertheless, for both species, clonal integration overwhelmed light effect in promoting the growth of juvenile ramets during early development. Also, vertical growth, as an apparent shade acclimation response, was more prevalent in severed ramets than in connected ramets. Finally, unrooted branches displayed smaller organ size and slower growth than connected ramets, but the pattern of light reaction was similar, suggesting mother plants invest in daughter ramets prior to their own branches. Conclusions Clonal integration modifies light reaction norms of morphological and growth traits in a species-specific manner for A. philoxeroides and P. canescens, but it improves the establishment of juvenile ramets of both species in light-limiting environments by promoting their growth during early development. This factor may be partially

  12. PyClone: statistical inference of clonal population structure in cancer.

    PubMed

    Roth, Andrew; Khattra, Jaswinder; Yap, Damian; Wan, Adrian; Laks, Emma; Biele, Justina; Ha, Gavin; Aparicio, Samuel; Bouchard-Côté, Alexandre; Shah, Sohrab P

    2014-04-01

    We introduce PyClone, a statistical model for inference of clonal population structures in cancers. PyClone is a Bayesian clustering method for grouping sets of deeply sequenced somatic mutations into putative clonal clusters while estimating their cellular prevalences and accounting for allelic imbalances introduced by segmental copy-number changes and normal-cell contamination. Single-cell sequencing validation demonstrates PyClone's accuracy.

  13. Parallel optical sampler

    DOEpatents

    Tauke-Pedretti, Anna; Skogen, Erik J; Vawter, Gregory A

    2014-05-20

    An optical sampler includes a first and second 1.times.n optical beam splitters splitting an input optical sampling signal and an optical analog input signal into n parallel channels, respectively, a plurality of optical delay elements providing n parallel delayed input optical sampling signals, n photodiodes converting the n parallel optical analog input signals into n respective electrical output signals, and n optical modulators modulating the input optical sampling signal or the optical analog input signal by the respective electrical output signals, and providing n successive optical samples of the optical analog input signal. A plurality of output photodiodes and eADCs convert the n successive optical samples to n successive digital samples. The optical modulator may be a photodiode interconnected Mach-Zehnder Modulator. A method of sampling the optical analog input signal is disclosed.

  14. Chromosome aberrations of clonal origin are present in astronauts' blood lymphocytes

    NASA Technical Reports Server (NTRS)

    George, K.; Durante, M.; Willingham, V.; Cucinotta, F. A.

    2004-01-01

    Radiation-induced chromosome translocations remain in peripheral blood cells over many years, and can potentially be used to measure retrospective doses or prolonged low-dose rate exposures. However, several recent studies have indicated that some individuals possess clones of cells with balanced chromosome abnormalities, which can result in an overestimation of damage and, therefore, influence the accuracy of dose calculations. We carefully examined the patterns of chromosome damage found in the blood lymphocytes of twelve astronauts, and also applied statistical methods to screen for the presence of potential clones. Cells with clonal aberrations were identified in three of the twelve individuals. These clonal cells were present in samples collected both before and after space flight, and yields are higher than previously reported for healthy individuals in this age range (40-52 years of age). The frequency of clonal damage appears to be even greater in chromosomes prematurely condensed in interphase, when compared with equivalent analysis in metaphase cells. The individuals with clonal aberrations were followed-up over several months and the yields of all clones decreased during this period. Since clonal aberrations may be associated with increased risk of tumorigenesis, it is important to accurately identify cells containing clonal rearrangements for risk assessment as well as biodosimetry. Copyright 2003 S. Karger AG, Basel.

  15. Plant Clonal Integration Mediates the Horizontal Redistribution of Soil Resources, Benefiting Neighboring Plants

    PubMed Central

    Ye, Xue-Hua; Zhang, Ya-Lin; Liu, Zhi-Lan; Gao, Shu-Qin; Song, Yao-Bin; Liu, Feng-Hong; Dong, Ming

    2016-01-01

    Resources such as water taken up by plants can be released into soils through hydraulic redistribution and can also be translocated by clonal integration within a plant clonal network. We hypothesized that the resources from one (donor) microsite could be translocated within a clonal network, released into different (recipient) microsites and subsequently used by neighbor plants in the recipient microsite. To test these hypotheses, we conducted two experiments in which connected and disconnected ramet pairs of Potentilla anserina were grown under both homogeneous and heterogeneous water regimes, with seedlings of Artemisia ordosica as neighbors. The isotopes [15N] and deuterium were used to trace the translocation of nitrogen and water, respectively, within the clonal network. The water and nitrogen taken up by P. anserina ramets in the donor microsite were translocated into the connected ramets in the recipient microsites. Most notably, portions of the translocated water and nitrogen were released into the recipient microsite and were used by the neighboring A. ordosica, which increased growth of the neighboring A. ordosica significantly. Therefore, our hypotheses were supported, and plant clonal integration mediated the horizontal hydraulic redistribution of resources, thus benefiting neighboring plants. Such a plant clonal integration-mediated resource redistribution in horizontal space may have substantial effects on the interspecific relations and composition of the community and consequently on ecosystem processes. PMID:26904051

  16. Gene Loss Dominates As a Source of Genetic Variation within Clonal Pathogenic Bacterial Species.

    PubMed

    Bolotin, Evgeni; Hershberg, Ruth

    2015-07-10

    Some of the most dangerous pathogens such as Mycobacterium tuberculosis and Yersinia pestis evolve clonally. This means that little or no recombination occurs between strains belonging to these species. Paradoxically, although different members of these species show extreme sequence similarity of orthologous genes, some show considerable intraspecies phenotypic variation, the source of which remains elusive. To examine the possible sources of phenotypic variation within clonal pathogenic bacterial species, we carried out an extensive genomic and pan-genomic analysis of the sources of genetic variation available to a large collection of clonal and nonclonal pathogenic bacterial species. We show that while nonclonal species diversify through a combination of changes to gene sequences, gene loss and gene gain, gene loss completely dominates as a source of genetic variation within clonal species. Indeed, gene loss is so prevalent within clonal species as to lead to levels of gene content variation comparable to those found in some nonclonal species that are much more diverged in their gene sequences and that acquire a substantial number of genes horizontally. Gene loss therefore needs to be taken into account as a potential dominant source of phenotypic variation within clonal bacterial species.

  17. Resource heterogeneity, soil fertility, and species diversity: effects of clonal species on plant communities.

    PubMed

    Eilts, J Alexander; Mittelbach, Gary G; Reynolds, Heather L; Gross, Katherine L

    2011-05-01

    Spatial heterogeneity in soil resources is widely thought to promote plant species coexistence, and this mechanism figures prominently in resource-ratio models of competition. However, most experimental studies have found that nutrient enhancements depress diversity regardless of whether nutrients are uniformly or heterogeneously applied. This mismatch between theory and empirical pattern is potentially due to an interaction between plant size and the scale of resource heterogeneity. Clonal plants that spread vegetatively via rhizomes or stolons can grow large and may integrate across resource patches, thus reducing the positive effect of small-scale resource heterogeneity on plant species richness. Many rhizomatous clonal species respond strongly to increased soil fertility, and they have been hypothesized to drive the descending arm of the hump-shaped productivity-diversity relationship in grasslands. We tested whether clonals reduce species richness in a grassland community by manipulating nutrient heterogeneity, soil fertility, and the presence of rhizomatous clonal species in a 6-year field experiment. We found strong and consistent negative effects of clonals on species richness. These effects were greatest at high fertility and when soil resources were applied at a scale at which rhizomatous clonals could integrate across resource patches. Thus, we find support for the hypothesis that plant size and resource heterogeneity interact to determine species diversity.

  18. Production and verification of a 2nd generation clonal group of Japanese flounder, Paralichthys olivaceus

    PubMed Central

    Hou, Jilun; Zhang, Xiaoyan; Wang, Yufen; Sun, Zhaohui; Si, Fei; Jiang, Xiufeng; Liu, Haijin

    2016-01-01

    Clonal fishes are useful tools in biology and aquaculture studies due to their isogenicity. In Japanese flounder (Paralichthys olivaceus), a group of homozygous clones was created by inducing meiogynogenesis in eggs from a mitogynogenetic homozygous diploid. As the clones reached sexual maturity, meiogynogenesis was again induced in order to produce a 2nd generation clonal group of Japanese flounder. After 3 months, there were 611 healthy, surviving individuals. Twenty-four microsatellite markers, that covered all the linkage groups of Japanese flounder, were used to identify the homozygosity of the 2nd generation clones; no heterozygous locus was detected. This indicates that the production of a 2nd generation clonal group of Japanese flounder was successful. Restriction-site DNA associated sequencing at the genomic level also confirmed the homozygosity and clonality of the 2nd generation clonal group. Furthermore, these 2nd generation clones had a small coefficient of variation for body shape indices at 210 days of age and showed a high degree of similarity in body characteristics among individuals. The successful production of 2nd generation clones has laid the foundation for the large-scale production of clonal Japanese flounder. PMID:27767055

  19. CRUNCH_PARALLEL

    SciTech Connect

    Shumaker, Dana E.; Steefel, Carl I.

    2016-06-21

    The code CRUNCH_PARALLEL is a parallel version of the CRUNCH code. CRUNCH code version 2.0 was previously released by LLNL, (UCRL-CODE-200063). Crunch is a general purpose reactive transport code developed by Carl Steefel and Yabusake (Steefel Yabsaki 1996). The code handles non-isothermal transport and reaction in one, two, and three dimensions. The reaction algorithm is generic in form, handling an arbitrary number of aqueous and surface complexation as well as mineral dissolution/precipitation. A standardized database is used containing thermodynamic and kinetic data. The code includes advective, dispersive, and diffusive transport.

  20. The NAS Parallel Benchmarks

    SciTech Connect

    Bailey, David H.

    2009-11-15

    The NAS Parallel Benchmarks (NPB) are a suite of parallel computer performance benchmarks. They were originally developed at the NASA Ames Research Center in 1991 to assess high-end parallel supercomputers. Although they are no longer used as widely as they once were for comparing high-end system performance, they continue to be studied and analyzed a great deal in the high-performance computing community. The acronym 'NAS' originally stood for the Numerical Aeronautical Simulation Program at NASA Ames. The name of this organization was subsequently changed to the Numerical Aerospace Simulation Program, and more recently to the NASA Advanced Supercomputing Center, although the acronym remains 'NAS.' The developers of the original NPB suite were David H. Bailey, Eric Barszcz, John Barton, David Browning, Russell Carter, LeoDagum, Rod Fatoohi, Samuel Fineberg, Paul Frederickson, Thomas Lasinski, Rob Schreiber, Horst Simon, V. Venkatakrishnan and Sisira Weeratunga. The original NAS Parallel Benchmarks consisted of eight individual benchmark problems, each of which focused on some aspect of scientific computing. The principal focus was in computational aerophysics, although most of these benchmarks have much broader relevance, since in a much larger sense they are typical of many real-world scientific computing applications. The NPB suite grew out of the need for a more rational procedure to select new supercomputers for acquisition by NASA. The emergence of commercially available highly parallel computer systems in the late 1980s offered an attractive alternative to parallel vector supercomputers that had been the mainstay of high-end scientific computing. However, the introduction of highly parallel systems was accompanied by a regrettable level of hype, not only on the part of the commercial vendors but even, in some cases, by scientists using the systems. As a result, it was difficult to discern whether the new systems offered any fundamental performance advantage

  1. Highly parallel computation

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.; Tichy, Walter F.

    1990-01-01

    Among the highly parallel computing architectures required for advanced scientific computation, those designated 'MIMD' and 'SIMD' have yielded the best results to date. The present development status evaluation of such architectures shown neither to have attained a decisive advantage in most near-homogeneous problems' treatment; in the cases of problems involving numerous dissimilar parts, however, such currently speculative architectures as 'neural networks' or 'data flow' machines may be entailed. Data flow computers are the most practical form of MIMD fine-grained parallel computers yet conceived; they automatically solve the problem of assigning virtual processors to the real processors in the machine.

  2. Adaptive parallel logic networks

    NASA Technical Reports Server (NTRS)

    Martinez, Tony R.; Vidal, Jacques J.

    1988-01-01

    Adaptive, self-organizing concurrent systems (ASOCS) that combine self-organization with massive parallelism for such applications as adaptive logic devices, robotics, process control, and system malfunction management, are presently discussed. In ASOCS, an adaptive network composed of many simple computing elements operating in combinational and asynchronous fashion is used and problems are specified by presenting if-then rules to the system in the form of Boolean conjunctions. During data processing, which is a different operational phase from adaptation, the network acts as a parallel hardware circuit.

  3. Parallel Coordinate Axes.

    ERIC Educational Resources Information Center

    Friedlander, Alex; And Others

    1982-01-01

    Several methods of numerical mappings other than the usual cartesian coordinate system are considered. Some examples using parallel axes representation, which are seen to lead to aesthetically pleasing or interesting configurations, are presented. Exercises with alternative representations can stimulate pupil imagination and exploration in…

  4. Parallel programming with PCN

    SciTech Connect

    Foster, I.; Tuecke, S.

    1993-01-01

    PCN is a system for developing and executing parallel programs. It comprises a high-level programming language, tools for developing and debugging programs in this language, and interfaces to Fortran and Cthat allow the reuse of existing code in multilingual parallel programs. Programs developed using PCN are portable across many different workstations, networks, and parallel computers. This document provides all the information required to develop parallel programs with the PCN programming system. It includes both tutorial and reference material. It also presents the basic concepts that underlie PCN, particularly where these are likely to be unfamiliar to the reader, and provides pointers to other documentation on the PCN language, programming techniques, and tools. PCN is in the public domain. The latest version of both the software and this manual can be obtained by anonymous ftp from Argonne National Laboratory in the directory pub/pcn at info.mcs. ani.gov (cf. Appendix A). This version of this document describes PCN version 2.0, a major revision of the PCN programming system. It supersedes earlier versions of this report.

  5. Parallel Dislocation Simulator

    SciTech Connect

    2006-10-30

    ParaDiS is software capable of simulating the motion, evolution, and interaction of dislocation networks in single crystals using massively parallel computer architectures. The software is capable of outputting the stress-strain response of a single crystal whose plastic deformation is controlled by the dislocation processes.

  6. Massively parallel processor computer

    NASA Technical Reports Server (NTRS)

    Fung, L. W. (Inventor)

    1983-01-01

    An apparatus for processing multidimensional data with strong spatial characteristics, such as raw image data, characterized by a large number of parallel data streams in an ordered array is described. It comprises a large number (e.g., 16,384 in a 128 x 128 array) of parallel processing elements operating simultaneously and independently on single bit slices of a corresponding array of incoming data streams under control of a single set of instructions. Each of the processing elements comprises a bidirectional data bus in communication with a register for storing single bit slices together with a random access memory unit and associated circuitry, including a binary counter/shift register device, for performing logical and arithmetical computations on the bit slices, and an I/O unit for interfacing the bidirectional data bus with the data stream source. The massively parallel processor architecture enables very high speed processing of large amounts of ordered parallel data, including spatial translation by shifting or sliding of bits vertically or horizontally to neighboring processing elements.

  7. High performance parallel architectures

    SciTech Connect

    Anderson, R.E. )

    1989-09-01

    In this paper the author describes current high performance parallel computer architectures. A taxonomy is presented to show computer architecture from the user programmer's point-of-view. The effects of the taxonomy upon the programming model are described. Some current architectures are described with respect to the taxonomy. Finally, some predictions about future systems are presented. 5 refs., 1 fig.

  8. Parallel fast gauss transform

    SciTech Connect

    Sampath, Rahul S; Sundar, Hari; Veerapaneni, Shravan

    2010-01-01

    We present fast adaptive parallel algorithms to compute the sum of N Gaussians at N points. Direct sequential computation of this sum would take O(N{sup 2}) time. The parallel time complexity estimates for our algorithms are O(N/n{sub p}) for uniform point distributions and O( (N/n{sub p}) log (N/n{sub p}) + n{sub p}log n{sub p}) for non-uniform distributions using n{sub p} CPUs. We incorporate a plane-wave representation of the Gaussian kernel which permits 'diagonal translation'. We use parallel octrees and a new scheme for translating the plane-waves to efficiently handle non-uniform distributions. Computing the transform to six-digit accuracy at 120 billion points took approximately 140 seconds using 4096 cores on the Jaguar supercomputer. Our implementation is 'kernel-independent' and can handle other 'Gaussian-type' kernels even when explicit analytic expression for the kernel is not known. These algorithms form a new class of core computational machinery for solving parabolic PDEs on massively parallel architectures.

  9. Parallel hierarchical radiosity rendering

    SciTech Connect

    Carter, M.

    1993-07-01

    In this dissertation, the step-by-step development of a scalable parallel hierarchical radiosity renderer is documented. First, a new look is taken at the traditional radiosity equation, and a new form is presented in which the matrix of linear system coefficients is transformed into a symmetric matrix, thereby simplifying the problem and enabling a new solution technique to be applied. Next, the state-of-the-art hierarchical radiosity methods are examined for their suitability to parallel implementation, and scalability. Significant enhancements are also discovered which both improve their theoretical foundations and improve the images they generate. The resultant hierarchical radiosity algorithm is then examined for sources of parallelism, and for an architectural mapping. Several architectural mappings are discussed. A few key algorithmic changes are suggested during the process of making the algorithm parallel. Next, the performance, efficiency, and scalability of the algorithm are analyzed. The dissertation closes with a discussion of several ideas which have the potential to further enhance the hierarchical radiosity method, or provide an entirely new forum for the application of hierarchical methods.

  10. Parallel hierarchical global illumination

    SciTech Connect

    Snell, Quinn O.

    1997-10-08

    Solving the global illumination problem is equivalent to determining the intensity of every wavelength of light in all directions at every point in a given scene. The complexity of the problem has led researchers to use approximation methods for solving the problem on serial computers. Rather than using an approximation method, such as backward ray tracing or radiosity, the authors have chosen to solve the Rendering Equation by direct simulation of light transport from the light sources. This paper presents an algorithm that solves the Rendering Equation to any desired accuracy, and can be run in parallel on distributed memory or shared memory computer systems with excellent scaling properties. It appears superior in both speed and physical correctness to recent published methods involving bidirectional ray tracing or hybrid treatments of diffuse and specular surfaces. Like progressive radiosity methods, it dynamically refines the geometry decomposition where required, but does so without the excessive storage requirements for ray histories. The algorithm, called Photon, produces a scene which converges to the global illumination solution. This amounts to a huge task for a 1997-vintage serial computer, but using the power of a parallel supercomputer significantly reduces the time required to generate a solution. Currently, Photon can be run on most parallel environments from a shared memory multiprocessor to a parallel supercomputer, as well as on clusters of heterogeneous workstations.

  11. Parallel Multigrid Equation Solver

    SciTech Connect

    Adams, Mark

    2001-09-07

    Prometheus is a fully parallel multigrid equation solver for matrices that arise in unstructured grid finite element applications. It includes a geometric and an algebraic multigrid method and has solved problems of up to 76 mullion degrees of feedom, problems in linear elasticity on the ASCI blue pacific and ASCI red machines.

  12. Clonal distribution of pneumococcal serotype 19F isolates from Ghana.

    PubMed

    Sparding, Nadja; Dayie, Nicholas T K D; Mills, Richael O; Newman, Mercy J; Dalsgaard, Anders; Frimodt-Møller, Niels; Slotved, Hans-Christian

    2015-04-01

    Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal strains are classified according to their capsular polysaccharide and more than 90 different serotypes are currently known. In this project, three distinct groups of pneumococcal carriage isolates from Ghana were investigated; isolates from healthy children in Tamale and isolates from both healthy and children attending the outpatient department at a hospital in Accra. The isolates were previously identified and characterized by Gram staining, serotyping and susceptibility to penicillin. In this study, isolates of the common serotype 19F were further investigated by Multi-Locus Sequence Typing (MLST). Overall, 14 different Sequence Types (STs) were identified by MLST, of which nine were novel based on the international MLST database. Two clones within serotype 19F seem to circulate in Ghana, a known ST (ST 4194) and a novel ST (ST 9090). ST 9090 was only found in healthy children in Accra, whereas ST 4194 was found equally in all children studied. In the MLST database, other isolates of ST 4194 were also associated with serotype 19F, and these isolates came from other West African countries. The majority of isolates were penicillin intermediate resistant. In conclusion, two clones within serotype 19F were found to be dominating in pneumococcal carriage in Accra and Tamale in Ghana. Furthermore, it seems as though the clonal distribution of serotype 19F may be different from what is currently known in Ghana in that many new clones were identified. This supports the importance of continued monitoring of pneumococcal carriage in Ghana and elsewhere when vaccines, e.g., PCV-13, have been introduced to monitor the possible future spread of antimicrobial resistant clones.

  13. FREQUENT CLONALITY IN FUCOIDS (FUCUS RADICANS AND FUCUS VESICULOSUS; FUCALES, PHAEOPHYCEAE) IN THE BALTIC SEA(1).

    PubMed

    Johannesson, Kerstin; Johansson, Daniel; Larsson, Karl H; Huenchuñir, Cecilia J; Perus, Jens; Forslund, Helena; Kautsky, Lena; Pereyra, Ricardo T

    2011-10-01

    Asexual reproduction by cloning may affect the genetic structure of populations, their potential to evolve, and, among foundation species, contributions to ecosystem functions. Macroalgae of the genus Fucus are known to produce attached plants only by sexual recruitment. Recently, however, clones of attached plants recruited by asexual reproduction were observed in a few populations of Fucus radicans Bergström et L. Kautsky and F. vesiculosus L. inside the Baltic Sea. Herein we assess the distribution and prevalence of clonality in Baltic fucoids using nine polymorphic microsatellite loci and samples of F. radicans and F. vesiculosus from 13 Baltic sites. Clonality was more common in F. radicans than in F. vesiculosus, and in both species it tended to be most common in northern Baltic sites, although variation among close populations was sometimes extensive. Individual clonal lineages were mostly restricted to single or nearby locations, but one clonal lineage of F. radicans dominated five of 10 populations and was widely distributed over 550 × 100 km of coast. Populations dominated by a few clonal lineages were common in F. radicans, and these were less genetically variable than in other populations. As thalli recruited by cloning produced gametes, a possible explanation for this reduced genetic variation is that dominance of one or a few clonal lineages biases the gamete pool resulting in a decreased effective population size and thereby loss of genetic variation by genetic drift. Baltic fucoids are important habitat-forming species, and genetic structure and presence of clonality have implications for conservation strategies.

  14. Stochastic simulation of clonal growth in the tall goldenrod, Solidago altissima.

    PubMed

    Cain, M L; Pacala, S W; Silander, J A

    1991-12-01

    As clonal plants grow they move through space. The movement patterns that result can be complex and difficult to interpret without the aid of models. We developed a stochastic simulation model of clonal growth in the tall goldenrod, Solidago altissima. Our model was calibrated with field data on the clonal expansion of both seedlings and established clones, and model assumptions were verified by statistical analyses.When simulations were based on empirical distributions with long rhizome lengths, there was greater dispersal, less leaf overlap, and less spatial aggregation than when simulations were based on distributions with comparatively short rhizome lengths. For the field data that we utilized, variation in rhizome lengths had a greater effect than variation for either branching angles or "rhizome initiation points" (see text). We also found that observed patterns of clonal growth in S. altissima did not cause the formation of "fairy rings". However, simulations with an artificial distribution of branching angles demonstrate that "fairy rings" can result solely from a plant's clonal morphology.Stochastic simulation models that incorporated variation in rhizome lengths, branching angles, and rhizome initiation points produced greater dispersal and less leaf overlap than deterministic models. Thus, variation for clonal growth parameters may increase the efficiency of substrate exploration by increasing the area covered and by decreasing the potential for intraclonal competition. We also demonstrated that ramet displacements were slightly, but consistently lower in stochastic simulation models than in random-walk models. This difference was due to the incorporation of details on rhizome bud initiation into stochastic simulation models, but not random-walk models. We discuss the advantages and disadvantages of deterministic, stochastic simulation, and random-walk models of clonal growth.

  15. Clonal Patch Size and Ramet Position of Leymus chinensis Affected Reproductive Allocation

    PubMed Central

    Zhang, Zhuo; Yang, Yunfei

    2015-01-01

    Reproductive allocation is critically important for population maintenance and usually varies with not only environmental factors but also biotic ones. As a typical rhizome clonal plant in China's northern grasslands, Leymus chinensis usually dominates the steppe communities and grows in clonal patches. In order to clarify the sexual reproductive allocation of L. chinensis in the process of the growth and expansion, we selected L. chinensis clonal patches of a range of sizes to examine the reproductive allocation and allometric growth of the plants. Moreover, the effects of position of L. chinensis ramets within the patch on their reproductive allocation were also examined. Clonal patch size and position both significantly affected spike biomass, reproductive tiller biomass and SPIKE/TILLER biomass ratio. From the central to the marginal zone, both the spike biomass and reproductive tiller biomass displayed an increasing trend in all the five patch size categories except for reproductive tiller biomass in 15–40m2 category. L. chinensis had significantly larger SPIKE/TILLER biomass ratio in marginal zone than in central zone of clonal patches that are larger than 15 m2 in area. Regression analysis showed that the spike biomass and SPIKE/TILLER biomass ratio were negatively correlated with clonal patch size while patch size showed significantly positive effect on SEED/SPIKE biomass ratio, but the reproductive tiller biomass and SEED/TILLER biomass ratio were not dependent on clonal patch size. The relationships between biomass of spike and reproductive tiller, between mature seed biomass and spike biomass and between mature seed biomass and reproductive tiller biomass were significant allometric for all or some of patch size categories, respectively. The slopes of all these allometric relationships were significantly different from 1. The allometric growth of L. chinensis is patch size-dependent. This finding will be helpful for developing appropriate practices for

  16. Phylogenetic meta-analysis of the functional traits of clonal plants foraging in changing environments.

    PubMed

    Xie, Xiu-Fang; Song, Yao-Bin; Zhang, Ya-Lin; Pan, Xu; Dong, Ming

    2014-01-01

    Foraging behavior, one of the adaptive strategies of clonal plants, has stimulated a tremendous amount of research. However, it is a matter of debate whether there is any general pattern in the foraging traits (functional traits related to foraging behavior) of clonal plants in response to diverse environments. We collected data from 97 published papers concerning the relationships between foraging traits (e.g., spacer length, specific spacer length, branch intensity and branch angle) of clonal plants and essential resources (e.g., light, nutrients and water) for plant growth and reproduction. We incorporated the phylogenetic information of 85 plant species to examine the universality of foraging hypotheses using phylogenetic meta-analysis. The trends toward forming longer spacers and fewer branches in shaded environments were detected in clonal plants, but no evidence for a relation between foraging traits and nutrient availability was detected, except that there was a positive correlation between branch intensity and nutrient availability in stoloniferous plants. The response of the foraging traits of clonal plants to water availability was also not obvious. Additionally, our results indicated that the foraging traits of stoloniferous plants were more sensitive to resource availability than those of rhizomatous plants. In consideration of plant phylogeny, these results implied that the foraging traits of clonal plants (notably stoloniferous plants) only responded to light intensity in a general pattern but did not respond to nutrient or water availability. In conclusion, our findings on the effects of the environment on the foraging traits of clonal plants avoided the confounding effects of phylogeny because we incorporated phylogeny into the meta-analysis.

  17. Analysis of non-clonal chromosome abnormalities observed in hematologic malignancies among Southwest Oncology Group patients

    SciTech Connect

    McConnell, T.S.; Dobin, S.M.

    1994-09-01

    From 1987-1994, the Southwest Oncology Group Cytogenetics Committee reviewed 1571 studies in 590 adult patient cases with ALL, AML, CML or CLL. These were analyzed for the presence of clinically important non-clonal abnormalities (NCA). Abnormalities were defined as non-clonal if one metaphase had a structural abnormality or an extra chromosome. Chromosome loss was not analyzed due to the possibility of random loss. In 72 cases (12%) comprising 136 studies, at least one NCA was observed. In 21 of these cases (29%), NCAs consisted of obvious clonal evolution or instability, and thus were not included in the analysis. At least one structural NCA was observed in which the abnormality differed from the mainline in 36 (50%) patients. Seventeen of the 36 cases had a normal mode. Nineteen of the 36 patients had an abnormal or normal/abnormal mode. At least one numerical NCA was found in 15 cases (21%). Fifteen cases (21%) contained at least one marker chromosome. Several cases involved NCA in more than one of the above divisions. NCAs could be classified into several categories: (1){open_quotes}the clone to come{close_quotes}, (2) evolving clones which then disappeared, (3) NCAs with putative clinical importance that never became clonal, (4) NCAs during remission identical to the preceding clonal abnormality, (5) NCAs which indicated clonal evolution or instability. Examples include one metaphase with t(9;22) or del(20q) or inv(16) or +8 which either preceded or followed clonal findings of the same aberration. Such findings should be communicated to the clinician.

  18. Clonal growth and fine-scale genetic structure in tanoak (Notholithocarpus densiflorus: Fagaceae).

    PubMed

    Dodd, Richard S; Mayer, Wasima; Nettel, Alejandro; Afzal-Rafii, Zara

    2013-01-01

    The combination of sprouting and reproduction by seed can have important consequences on fine-scale spatial distribution of genetic structure (SGS). SGS is an important consideration for species' restoration because it determines the minimum distance among seed trees to maximize genetic diversity while not prejudicing locally adapted genotypes. Local environmental conditions can be expected to influence levels of clonal spread and SGS, particularly in the case of disturbance regimes such as fire. Here, we characterize fine-scale genetic structure and clonal spread in tanoak from drier upland sites and more mesic lowland woodlands. Clonal spread was a significant mode of stand development, but spread was limited on average to about 5-6 m. Gene dispersal was decomposed into clonal and sexual components. The latter varied according to whether it was estimated from all ramets with the clonal component removed or for a single ramet per genet. We used the difference in these 2 estimates of gene dispersal as a measure of the effect of clonality on effective population size in this species. Although upland sites had a greater number of ramets per genet, most of the other indices computed were not significantly different. However, they tended to show greater heterozygote excess and shorter gene dispersal distances than the lowland sites. The average distance among inferred sibships on upland sites was approximately at the scale of maximum clonal range. This was not the case on lowland sites, where sibs were more dispersed. We recommend minimum distances among seed trees to avoid selecting clones and to maximize genetic diversity for restoration.

  19. Parallel grid population

    DOEpatents

    Wald, Ingo; Ize, Santiago

    2015-07-28

    Parallel population of a grid with a plurality of objects using a plurality of processors. One example embodiment is a method for parallel population of a grid with a plurality of objects using a plurality of processors. The method includes a first act of dividing a grid into n distinct grid portions, where n is the number of processors available for populating the grid. The method also includes acts of dividing a plurality of objects into n distinct sets of objects, assigning a distinct set of objects to each processor such that each processor determines by which distinct grid portion(s) each object in its distinct set of objects is at least partially bounded, and assigning a distinct grid portion to each processor such that each processor populates its distinct grid portion with any objects that were previously determined to be at least partially bounded by its distinct grid portion.

  20. Parallel Anisotropic Tetrahedral Adaptation

    NASA Technical Reports Server (NTRS)

    Park, Michael A.; Darmofal, David L.

    2008-01-01

    An adaptive method that robustly produces high aspect ratio tetrahedra to a general 3D metric specification without introducing hybrid semi-structured regions is presented. The elemental operators and higher-level logic is described with their respective domain-decomposed parallelizations. An anisotropic tetrahedral grid adaptation scheme is demonstrated for 1000-1 stretching for a simple cube geometry. This form of adaptation is applicable to more complex domain boundaries via a cut-cell approach as demonstrated by a parallel 3D supersonic simulation of a complex fighter aircraft. To avoid the assumptions and approximations required to form a metric to specify adaptation, an approach is introduced that directly evaluates interpolation error. The grid is adapted to reduce and equidistribute this interpolation error calculation without the use of an intervening anisotropic metric. Direct interpolation error adaptation is illustrated for 1D and 3D domains.

  1. Parallel Subconvolution Filtering Architectures

    NASA Technical Reports Server (NTRS)

    Gray, Andrew A.

    2003-01-01

    These architectures are based on methods of vector processing and the discrete-Fourier-transform/inverse-discrete- Fourier-transform (DFT-IDFT) overlap-and-save method, combined with time-block separation of digital filters into frequency-domain subfilters implemented by use of sub-convolutions. The parallel-processing method implemented in these architectures enables the use of relatively small DFT-IDFT pairs, while filter tap lengths are theoretically unlimited. The size of a DFT-IDFT pair is determined by the desired reduction in processing rate, rather than on the order of the filter that one seeks to implement. The emphasis in this report is on those aspects of the underlying theory and design rules that promote computational efficiency, parallel processing at reduced data rates, and simplification of the designs of very-large-scale integrated (VLSI) circuits needed to implement high-order filters and correlators.

  2. Parallel multilevel preconditioners

    SciTech Connect

    Bramble, J.H.; Pasciak, J.E.; Xu, Jinchao.

    1989-01-01

    In this paper, we shall report on some techniques for the development of preconditioners for the discrete systems which arise in the approximation of solutions to elliptic boundary value problems. Here we shall only state the resulting theorems. It has been demonstrated that preconditioned iteration techniques often lead to the most computationally effective algorithms for the solution of the large algebraic systems corresponding to boundary value problems in two and three dimensional Euclidean space. The use of preconditioned iteration will become even more important on computers with parallel architecture. This paper discusses an approach for developing completely parallel multilevel preconditioners. In order to illustrate the resulting algorithms, we shall describe the simplest application of the technique to a model elliptic problem.

  3. Ultrascalable petaflop parallel supercomputer

    DOEpatents

    Blumrich, Matthias A.; Chen, Dong; Chiu, George; Cipolla, Thomas M.; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Hall, Shawn; Haring, Rudolf A.; Heidelberger, Philip; Kopcsay, Gerard V.; Ohmacht, Martin; Salapura, Valentina; Sugavanam, Krishnan; Takken, Todd

    2010-07-20

    A massively parallel supercomputer of petaOPS-scale includes node architectures based upon System-On-a-Chip technology, where each processing node comprises a single Application Specific Integrated Circuit (ASIC) having up to four processing elements. The ASIC nodes are interconnected by multiple independent networks that optimally maximize the throughput of packet communications between nodes with minimal latency. The multiple networks may include three high-speed networks for parallel algorithm message passing including a Torus, collective network, and a Global Asynchronous network that provides global barrier and notification functions. These multiple independent networks may be collaboratively or independently utilized according to the needs or phases of an algorithm for optimizing algorithm processing performance. The use of a DMA engine is provided to facilitate message passing among the nodes without the expenditure of processing resources at the node.

  4. Homology, convergence and parallelism

    PubMed Central

    Ghiselin, Michael T.

    2016-01-01

    Homology is a relation of correspondence between parts of parts of larger wholes. It is used when tracking objects of interest through space and time and in the context of explanatory historical narratives. Homologues can be traced through a genealogical nexus back to a common ancestral precursor. Homology being a transitive relation, homologues remain homologous however much they may come to differ. Analogy is a relationship of correspondence between parts of members of classes having no relationship of common ancestry. Although homology is often treated as an alternative to convergence, the latter is not a kind of correspondence: rather, it is one of a class of processes that also includes divergence and parallelism. These often give rise to misleading appearances (homoplasies). Parallelism can be particularly hard to detect, especially when not accompanied by divergences in some parts of the body. PMID:26598721

  5. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

    PubMed Central

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C.; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W.; Böttcher, Sebastian; van Dongen, Jacques J.M.

    2015-01-01

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56low NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56low NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94hi/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality. PMID:26556869

  6. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality.

    PubMed

    Bárcena, Paloma; Jara-Acevedo, María; Tabernero, María Dolores; López, Antonio; Sánchez, María Luz; García-Montero, Andrés C; Muñoz-García, Noemí; Vidriales, María Belén; Paiva, Artur; Lecrevisse, Quentin; Lima, Margarida; Langerak, Anton W; Böttcher, Sebastian; van Dongen, Jacques J M; Orfao, Alberto; Almeida, Julia

    2015-12-15

    Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

  7. Parallel unstructured grid generation

    NASA Technical Reports Server (NTRS)

    Loehner, Rainald; Camberos, Jose; Merriam, Marshal

    1991-01-01

    A parallel unstructured grid generation algorithm is presented and implemented on the Hypercube. Different processor hierarchies are discussed, and the appropraite hierarchies for mesh generation and mesh smoothing are selected. A domain-splitting algorithm for unstructured grids which tries to minimize the surface-to-volume ratio of each subdomain is described. This splitting algorithm is employed both for grid generation and grid smoothing. Results obtained on the Hypercube demonstrate the effectiveness of the algorithms developed.

  8. Development of Parallel GSSHA

    DTIC Science & Technology

    2013-09-01

    C en te r Paul R. Eller , Jing-Ru C. Cheng, Aaron R. Byrd, Charles W. Downer, and Nawa Pradhan September 2013 Approved for public release...Program ERDC TR-13-8 September 2013 Development of Parallel GSSHA Paul R. Eller and Jing-Ru C. Cheng Information Technology Laboratory US Army Engineer...5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Paul Eller , Ruth Cheng, Aaron Byrd, Chuck Downer, and Nawa Pradhan 5d. PROJECT NUMBER

  9. Xyce parallel electronic simulator.

    SciTech Connect

    Keiter, Eric R; Mei, Ting; Russo, Thomas V.; Rankin, Eric Lamont; Schiek, Richard Louis; Thornquist, Heidi K.; Fixel, Deborah A.; Coffey, Todd S; Pawlowski, Roger P; Santarelli, Keith R.

    2010-05-01

    This document is a reference guide to the Xyce Parallel Electronic Simulator, and is a companion document to the Xyce Users Guide. The focus of this document is (to the extent possible) exhaustively list device parameters, solver options, parser options, and other usage details of Xyce. This document is not intended to be a tutorial. Users who are new to circuit simulation are better served by the Xyce Users Guide.

  10. Massively Parallel Genetics.

    PubMed

    Shendure, Jay; Fields, Stanley

    2016-06-01

    Human genetics has historically depended on the identification of individuals whose natural genetic variation underlies an observable trait or disease risk. Here we argue that new technologies now augment this historical approach by allowing the use of massively parallel assays in model systems to measure the functional effects of genetic variation in many human genes. These studies will help establish the disease risk of both observed and potential genetic variants and to overcome the problem of "variants of uncertain significance."

  11. Parallel sphere rendering

    SciTech Connect

    Krogh, M.; Painter, J.; Hansen, C.

    1996-10-01

    Sphere rendering is an important method for visualizing molecular dynamics data. This paper presents a parallel algorithm that is almost 90 times faster than current graphics workstations. To render extremely large data sets and large images, the algorithm uses the MIMD features of the supercomputers to divide up the data, render independent partial images, and then finally composite the multiple partial images using an optimal method. The algorithm and performance results are presented for the CM-5 and the M.

  12. Implementation of Parallel Algorithms

    DTIC Science & Technology

    1993-06-30

    their socia ’ relations or to achieve some goals. For example, we define a pair-wise force law of i epulsion and attraction for a group of identical...quantization based compression schemes. Photo-refractive crystals, which provide high density recording in real time, are used as our holographic media . The...of Parallel Algorithms (J. Reif, ed.). Kluwer Academic Pu’ ishers, 1993. (4) "A Dynamic Separator Algorithm", D. Armon and J. Reif. To appear in

  13. GeneScanning analysis of Ig/TCR gene rearrangements to detect clonality in canine lymphomas.

    PubMed

    Gentilini, Fabio; Calzolari, Claudia; Turba, Maria E; Bettini, Giuliano; Famigli-Bergamini, Paolo

    2009-01-15

    The diagnosis of canine lymphoma is achieved using morphological and immunological methods. In a certain percentage of cases, difficulties in making a definitive diagnosis of lymphoproliferative disorders may occur despite extensive immunophenotyping. Therefore, additional diagnostics, such as molecular assessment of Ig/TCR gene rearrangements clonality, may confirm the final diagnosis. Polyacrylamide gel electrophoresis and heteroduplex analysis have already been proven to be suitable for detecting clonality but are cumbersome and labor-intensive. In the present study, GeneScanning analysis of PCR products originating from different primer sets targeting different regions of Ig and TCR was validated in improving sensitivity as well as in reducing the turnaround time of gene rearrangement assays. GeneScanning exploits 5' fluorescently labelled primers for the automated and fast analysis of PCR products either as singleplex or multiplex runs. Initially, the assay was set up using DNA purified from normal tissues (n=6), hyperplastic/reactive tissues (n=10) and a small set of immunophenotyped lymphoma samples (n=12). The optimized methods were then used in a large set of 96 canine lymphoma samples. Normal and hyperplastic/reactive lymphoid tissues showed typically polyclonal or, occasionally, oligoclonal PCR products. Lymphoma samples showed monoclonal peaks arranged as a single or, occasionally, a double narrow base peak sometimes embedded in a polyclonal background. In all immunophenotyped cases, an Ig or TCR clonal finding corresponded to B- and T-cell lymphomas, respectively. Overall, 94/96 (97.9%) samples showed clonal Ig/TCR clonal rearrangements among which clonal Ig was found in 61/96 (63.5%) of samples and clonal TCR in 33/35 Ig negative samples (34.4% of all cases). In one out of ten randomly chosen cases, both Ig and TCR clonal gene rearrangements were found. Among the factors affecting assay accuracy, DNA quality has been shown to be critical and the

  14. Mutational Profiling Can Establish Clonal or Independent Origin in Synchronous Bilateral Breast and Other Tumors

    PubMed Central

    Schwab, Richard; Harismendy, Olivier; Pu, Minya; Crain, Brian; Yost, Shawn; Frazer, Kelly A.; Rana, Brinda; Hasteh, Farnaz; Wallace, Anne; Parker, Barbara A.

    2015-01-01

    Background Synchronous tumors can be independent primary tumors or a primary-metastatic (clonal) pair, which may have clinical implications. Mutational profiling of tumor DNA is increasingly common in the clinic. We investigated whether mutational profiling can distinguish independent from clonal tumors in breast and other cancers, using a carefully defined test based on the Clonal Likelihood Score (CLS = 100 x # shared high confidence (HC) mutations/ # total HC mutations). Methods Statistical properties of a formal test using the CLS were investigated. A high CLS is evidence in favor of clonality; the test is implemented as a one-sided binomial test of proportions. Test parameters were empirically determined using 16,422 independent breast tumor pairs and 15 primary-metastatic tumor pairs from 10 cancer types using The Cancer Genome Atlas. Results We validated performance of the test with its established parameters, using five published data sets comprising 15,758 known independent tumor pairs (maximum CLS = 4.1%, minimum p-value = 0.48) and 283 known tumor clonal pairs (minimum CLS 13%, maximum p-value <0.01), across renal cell, testicular, and colorectal cancer. The CLS test correctly classified all validation samples but one, which it appears may have been incorrectly classified in the published data. As proof-of-concept we then applied the CLS test to two new cases of invasive synchronous bilateral breast cancer at our institution, each with one hormone receptor positive (ER+/PR+/HER2-) lobular and one triple negative ductal carcinoma. High confidence mutations were identified by exome sequencing and results were validated using deep targeted sequencing. The first tumor pair had CLS of 81% (p-value < 10–15), supporting clonality. In the second pair, no common mutations of 184 variants were validated (p-value >0.99), supporting independence. A plausible molecular mechanism for the shift from hormone receptor positive to triple negative was identified in the

  15. Spatial Genetic Structure and Clonal Diversity in an Alpine Population of Salix herbacea (Salicaceae)

    PubMed Central

    Reisch, Christoph; Schurm, Sophia; Poschlod, Peter

    2007-01-01

    Background and Aims Many alpine plant species combine clonal and sexual reproduction to minimize the risks of flowering and seed production in high mountain regions. The spatial genetic structure and diversity of these alpine species is strongly affected by different clonal strategies (phalanx or guerrilla) and the proportion of generative and vegetative reproduction. Methods The clonal structure of the alpine plant species Salix herbacea was investigated in a 3 × 3 m plot of an alpine meadow using microsatellite (simple sequence repeat; SSR) analysis. The data obtained were compared with the results of a random amplified polymorphic DNA (RAPD) analysis. Key Results SSR analysis, based on three loci and 16 alleles, revealed 24 different genotypes and a proportion of distinguishable genotypes of 0·18. Six SSR clones were found consisting of at least five samples, 17 clones consisting of more than two samples and seven single genotypes. Mean clone size comprising at least five samples was 0·96 m2, and spatial autocorrelation analysis showed strong similarity of samples up to 130 cm. RAPD analysis revealed a higher level of clonal diversity but a comparable number of larger clones and a similar spatial structure. Conclusions The spatial genetic structure as well as the occurrence of single genotypes revealed in this study suggests both clonal and sexual propagation and repeated seedling recruitment in established populations of S. herbacea and is thus suggestive of a relaxed phalanx strategy. PMID:17242040

  16. SNP/RD typing of Mycobacterium tuberculosis Beijing strains reveals local and worldwide disseminated clonal complexes.

    PubMed

    Schürch, Anita C; Kremer, Kristin; Hendriks, Amber C A; Freyee, Benthe; McEvoy, Christopher R E; van Crevel, Reinout; Boeree, Martin J; van Helden, Paul; Warren, Robin M; Siezen, Roland J; van Soolingen, Dick

    2011-01-01

    The Beijing strain is one of the most successful genotypes of Mycobacterium tuberculosis worldwide and appears to be highly homogenous according to existing genotyping methods. To type Beijing strains reliably we developed a robust typing scheme using single nucleotide polymorphisms (SNPs) and regions of difference (RDs) derived from whole-genome sequencing data of eight Beijing strains. SNP/RD typing of 259 M. tuberculosis isolates originating from 45 countries worldwide discriminated 27 clonal complexes within the Beijing genotype family. A total of 16 Beijing clonal complexes contained more than one isolate of known origin, of which two clonal complexes were strongly associated with South African origin. The remaining 14 clonal complexes encompassed isolates from different countries. Even highly resolved clonal complexes comprised isolates from distinct geographical sites. Our results suggest that Beijing strains spread globally on multiple occasions and that the tuberculosis epidemic caused by the Beijing genotype is at least partially driven by modern migration patterns. The SNPs and RDs presented in this study will facilitate future molecular epidemiological and phylogenetic studies on Beijing strains.

  17. The association between polyploidy and clonal reproduction in diploid and tetraploid Chamerion angustifolium.

    PubMed

    Baldwin, Sarah J; Husband, Brian C

    2013-04-01

    Clonal reproduction is associated with the incidence of polyploidy in flowering plants. This pattern may arise through selection for increased clonality in polyploids compared to diploids to reduce mixed-ploidy mating. Here, we test whether clonal reproduction is greater in tetraploid than diploid populations of the mixed-ploidy plant, Chamerion angustifolium, through an analysis of the size and spatial distribution of clones in natural populations using AFLP genotyping and a comparison of root bud production in a greenhouse study. Natural tetraploid populations (N = 5) had significantly more AFLP genotypes (x¯ = 10.8) than diploid populations (x¯ = 6.0). Tetraploid populations tended to have fewer ramets per genotype and fewer genotypes with >1 ramet. In a spatial autocorrelation analysis, ramets within genotypes were more spatially aggregated in diploid populations than in tetraploid populations. In the greenhouse, tetraploids allocated 90.4% more dry mass to root buds than diploids, but tetraploids produced no more root buds and 44% fewer root buds per unit root mass than diploids. Our results indicate that clonal reproduction is significant in most populations, but tetraploid populations are not more clonal than diploids, nor are their clones more spatially aggregated. As a result, tetraploids may be less sheltered from mixed-ploidy mating and diploids more exposed to inbreeding, the balance of which could influence the establishment of tetraploids in diploid populations.

  18. TNFα facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms

    PubMed Central

    Aichberger, Karl J.; Luty, Samuel B.; Bumm, Thomas G.; Petersen, Curtis L.; Doratotaj, Shirin; Vasudevan, Kavin B.; LaTocha, Dorian H.; Yang, Fei; Press, Richard D.; Loriaux, Marc M.; Pahl, Heike L.; Silver, Richard T.; Agarwal, Anupriya; O'Hare, Thomas; Druker, Brian J.; Bagby, Grover C.

    2011-01-01

    Proinflammatory cytokines such as TNFα are elevated in patients with myeloproliferative neoplasms (MPN), but their contribution to disease pathogenesis is unknown. Here we reveal a central role for TNFα in promoting clonal dominance of JAK2V617F expressing cells in MPN. We show that JAK2V617F kinase regulates TNFα expression in cell lines and primary MPN cells and TNFα expression is correlated with JAK2V617F allele burden. In clonogenic assays, normal controls show reduced colony formation in the presence of TNFα while colony formation by JAK2V617F-positive progenitor cells is resistant or stimulated by exposure to TNFα. Ectopic JAK2V617F expression confers TNFα resistance to normal murine progenitor cells and overcomes inherent TNFα hypersensitivity of Fanconi anemia complementation group C deficient progenitors. Lastly, absence of TNFα limits clonal expansion and attenuates disease in a murine model of JAK2V617F-positive MPN. Altogether our data are consistent with a model where JAK2V617F promotes clonal selection by conferring TNFα resistance to a preneoplastic TNFα sensitive cell, while simultaneously generating a TNFα-rich environment. Mutations that confer resistance to environmental stem cell stressors are a recognized mechanism of clonal selection and leukemogenesis in bone marrow failure syndromes and our data suggest that this mechanism is also critical to clonal selection in MPN. PMID:21860020

  19. Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults

    PubMed Central

    Young, Andrew L.; Challen, Grant A.; Birmann, Brenda M.; Druley, Todd E.

    2016-01-01

    Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones—>0.02 variant allele fraction (VAF)—due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50–60-year-old participants in the Nurses' Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin. PMID:27546487

  20. Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants.

    PubMed

    Koelle, Samson J; Espinoza, Diego A; Wu, Chuanfeng; Xu, Jason; Lu, Rong; Li, Brian; Donahue, Robert E; Dunbar, Cynthia E

    2017-03-16

    Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells, and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in 4 macaques observed for up to 49 months posttransplantation. A broad range of clonal behaviors characterized by contribution level and biases toward certain cell types were extremely stable over time. Correlations between granulocyte and monocyte clonalities were greatest, followed by correlations between these cell types and B cells. We also detected quantitative expansion of T cell-biased clones consistent with an adaptive immune response. In contrast to recent data from a nonquantitative murine model, there was little evidence for clonal succession after initial hematopoietic reconstitution. These findings have important implications for human hematopoiesis, given the similarities between macaque and human physiologies.

  1. Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing

    PubMed Central

    Hughes, Andrew E. O.; Magrini, Vincent; Demeter, Ryan; Miller, Christopher A.; Fulton, Robert; Fulton, Lucinda L.; Eades, William C.; Elliott, Kevin; Heath, Sharon; Westervelt, Peter; Ding, Li; Conrad, Donald F.; White, Brian S.; Shao, Jin; Link, Daniel C.; DiPersio, John F.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.; Walter, Matthew J.; Graubert, Timothy A.

    2014-01-01

    Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples. These analyses yield specific predictions—the population frequency of individual clones, their genetic composition, and their evolutionary relationships—which we set out to test by sequencing individual cells from three subjects diagnosed with secondary acute myeloid leukemia, each of whom had been previously characterized by whole genome sequencing of unfractionated tumor samples. Single-cell mutation profiling strongly supported the clonal architecture implied by the analysis of bulk material. In addition, it resolved the clonal assignment of single nucleotide variants that had been initially ambiguous and identified areas of previously unappreciated complexity. Accordingly, we find that many of the key assumptions underlying the analysis of tumor clonality by deep sequencing of unfractionated material are valid. Furthermore, we illustrate a single-cell sequencing strategy for interrogating the clonal relationships among known variants that is cost-effective, scalable, and adaptable to the analysis of both hematopoietic and solid tumors, or any heterogeneous population of cells. PMID:25010716

  2. Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing.

    PubMed

    Hughes, Andrew E O; Magrini, Vincent; Demeter, Ryan; Miller, Christopher A; Fulton, Robert; Fulton, Lucinda L; Eades, William C; Elliott, Kevin; Heath, Sharon; Westervelt, Peter; Ding, Li; Conrad, Donald F; White, Brian S; Shao, Jin; Link, Daniel C; DiPersio, John F; Mardis, Elaine R; Wilson, Richard K; Ley, Timothy J; Walter, Matthew J; Graubert, Timothy A

    2014-07-01

    Next-generation sequencing has been used to infer the clonality of heterogeneous tumor samples. These analyses yield specific predictions-the population frequency of individual clones, their genetic composition, and their evolutionary relationships-which we set out to test by sequencing individual cells from three subjects diagnosed with secondary acute myeloid leukemia, each of whom had been previously characterized by whole genome sequencing of unfractionated tumor samples. Single-cell mutation profiling strongly supported the clonal architecture implied by the analysis of bulk material. In addition, it resolved the clonal assignment of single nucleotide variants that had been initially ambiguous and identified areas of previously unappreciated complexity. Accordingly, we find that many of the key assumptions underlying the analysis of tumor clonality by deep sequencing of unfractionated material are valid. Furthermore, we illustrate a single-cell sequencing strategy for interrogating the clonal relationships among known variants that is cost-effective, scalable, and adaptable to the analysis of both hematopoietic and solid tumors, or any heterogeneous population of cells.

  3. Properties of calcium and potassium currents of clonal adrenocortical cells

    PubMed Central

    1989-01-01

    The ionic currents of clonal Y-1 adrenocortical cells were studied using the whole-cell variant of the patch-clamp technique. These cells had two major current components: a large outward current carried by K ions, and a small inward Ca current. The Ca current depended on the activity of two populations of Ca channels, slow (SD) and fast (FD) deactivating, that could be separated by their different closing time constants (at -80 mV, SD, 3.8 ms, and FD, 0.13 ms). These two kinds of channels also differed in (a) activation threshold (SD, approximately - 50 mV; FD, approximately -20 mV), (b) half-maximal activation (SD, between -15 and -10 mV; FD between +10 and +15 mV), and (c) inactivation time course (SD, fast; FD, slow). The total amplitude of the Ca current and the proportion of SD and FD channels varied from cell to cell. The amplitude of the K current was strongly dependent on the internal [Ca2+] and was almost abolished when internal [Ca2+] was less than 0.001 microM. The K current appeared to be independent, or only slightly dependent, of Ca influx. With an internal [Ca2+] of 0.1 microM, the activation threshold was -20 mV, and at +40 mV the half- time of activation was 9 ms. With 73 mM external K the closing time constant at -70 mV was approximately 3 ms. The outward current was also modulated by internal pH and Mg. At a constant pCa gamma a decrease of pH reduced the current amplitude, whereas the activation kinetics were not much altered. Removal of internal Mg produced a drastic decrease in the amplitude of the Ca-activated K current. It was also found that with internal [Ca2+] over 0.1 microM the K current underwent a time- dependent transformation characterized by a large increase in amplitude and in activation kinetics. PMID:2539432

  4. Trajectory optimization using parallel shooting method on parallel computer

    SciTech Connect

    Wirthman, D.J.; Park, S.Y.; Vadali, S.R.

    1995-03-01

    The efficiency of a parallel shooting method on a parallel computer for solving a variety of optimal control guidance problems is studied. Several examples are considered to demonstrate that a speedup of nearly 7 to 1 is achieved with the use of 16 processors. It is suggested that further improvements in performance can be achieved by parallelizing in the state domain. 10 refs.

  5. The Galley Parallel File System

    NASA Technical Reports Server (NTRS)

    Nieuwejaar, Nils; Kotz, David

    1996-01-01

    As the I/O needs of parallel scientific applications increase, file systems for multiprocessors are being designed to provide applications with parallel access to multiple disks. Many parallel file systems present applications with a conventional Unix-like interface that allows the application to access multiple disks transparently. The interface conceals the parallelism within the file system, which increases the ease of programmability, but makes it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. Furthermore, most current parallel file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic parallel workloads. We discuss Galley's file structure and application interface, as well as an application that has been implemented using that interface.

  6. Asynchronous interpretation of parallel microprograms

    SciTech Connect

    Bandman, O.L.

    1984-03-01

    In this article, the authors demonstrate how to pass from a given synchronous interpretation of a parallel microprogram to an equivalent asynchronous interpretation, and investigate the cost associated with the rejection of external synchronization in parallel microprogram structures.

  7. Status of TRANSP Parallel Services

    NASA Astrophysics Data System (ADS)

    Indireshkumar, K.; Andre, Robert; McCune, Douglas; Randerson, Lewis

    2006-10-01

    The PPPL TRANSP code suite has been used successfully over many years to carry out time dependent simulations of tokamak plasmas. However, accurately modeling certain phenomena such as RF heating and fast ion behavior using TRANSP requires extensive computational power and will benefit from parallelization. Parallelizing all of TRANSP is not required and parts will run sequentially while other parts run parallelized. To efficiently use a site's parallel services, the parallelized TRANSP modules are deployed to a shared ``parallel service'' on a separate cluster. The PPPL Monte Carlo fast ion module NUBEAM and the MIT RF module TORIC are the first TRANSP modules to be so deployed. This poster will show the performance scaling of these modules within the parallel server. Communications between the serial client and the parallel server will be described in detail, and measurements of startup and communications overhead will be shown. Physics modeling benefits for TRANSP users will be assessed.

  8. Resistor Combinations for Parallel Circuits.

    ERIC Educational Resources Information Center

    McTernan, James P.

    1978-01-01

    To help simplify both teaching and learning of parallel circuits, a high school electricity/electronics teacher presents and illustrates the use of tables of values for parallel resistive circuits in which total resistances are whole numbers. (MF)

  9. Sexual recombination punctuated by outbreaks and clonal expansions predicts Toxoplasma gondii population genetics

    PubMed Central

    Grigg, Michael E.; Sundar, Natarajan

    2009-01-01

    The cosmopolitan parasitic pathogen Toxoplasma gondii is capable of infecting essentially any warm-blooded vertebrate worldwide, including most birds and mammals, and establishes chronic infections in one-third of the globe’s human population. The success of this highly prevalent zoonosis is largely the result of its ability to propagate both sexually and clonally. Frequent genetic exchanges via sexual recombination among extant parasite lineages that mix in the definitive felid host produces new lines that emerge to expand the parasite’s host range and cause outbreaks. Highly successful lines spread clonally via carnivorism and in some cases sweep to pandemic levels. The extent to which sexual reproduction versus clonal expansion shapes Toxoplasma’s current, global population genetic structure is the central question this review will attempt to answer. PMID:19217909

  10. Clonal reproduction with androgenesis and somatic recombination: the case of the ant Cardiocondyla kagutsuchi.

    PubMed

    Okita, Ichiro; Tsuchida, Koji

    2016-04-01

    In haplodiploid insects such as ants, male sexuals develop from unfertilised haploid eggs, while female sexuals and workers develop from fertilized diploid eggs. However, some ant species do not exchange their gene pool between sexes; both male and female sexuals are clonally produced, while workers are sexually produced. To date, three ant species, Wasmannia auropunctata, Vollenhovia emeryi, and Paratrechina longicornis, have been reported to reproduce using such reproductive systems. In this study, we reveal that in one lineage of the ant Cardiocondyla kagutsuchi, male and female sexuals are also clonally produced. In contrast to the abovementioned three species, the workers were not only sexually produced but had recombinant sequences in their nuclear internal transcribed spacer regions, although the recombinant sequences were not detected in male or female sexuals. These results suggest that the lineage likely possesses a mechanism to compensate for the reduction in genetic variation due to clonal reproduction with somatic recombination that occurs within the workers.

  11. Different Growth Promoting Effects of Endophytic Bacteria on Invasive and Native Clonal Plants

    PubMed Central

    Dai, Zhi-Cong; Fu, Wei; Wan, Ling-Yun; Cai, Hong-Hong; Wang, Ning; Qi, Shan-Shan; Du, Dao-Lin

    2016-01-01

    The role of the interactions between endophytes and alien plants has been unclear yet in plant invasion. We used a completely germ-free culture system to quantify the plant growth-promoting (PGP) effects of endophytic bacteria Bacillus sp. on aseptic seedlings of Wedelia trilobata and of its native clonal congener W. chinensis. The endophytic bacteria did not affect the growth of W. chinensis, but they significantly promoted the growth of W. trilobata. With the PGP effects of endophytic bacteria, relative change ratios of the clonal traits and the ramets’ growth traits of W. trilobata were significantly greater than those of W. chinensis. Our results indicate that the growth-promoting effects of endophytes may differ between invasive and native clonal plants, and the endophytes of invasive plant may be host-specific to facilitate plant invasion. PMID:27252722

  12. ClonalFrameML: Efficient Inference of Recombination in Whole Bacterial Genomes

    PubMed Central

    Didelot, Xavier; Wilson, Daniel J.

    2015-01-01

    Recombination is an important evolutionary force in bacteria, but it remains challenging to reconstruct the imports that occurred in the ancestry of a genomic sample. Here we present ClonalFrameML, which uses maximum likelihood inference to simultaneously detect recombination in bacterial genomes and account for it in phylogenetic reconstruction. ClonalFrameML can analyse hundreds of genomes in a matter of hours, and we demonstrate its usefulness on simulated and real datasets. We find evidence for recombination hotspots associated with mobile elements in Clostridium difficile ST6 and a previously undescribed 310kb chromosomal replacement in Staphylococcus aureus ST582. ClonalFrameML is freely available at http://clonalframeml.googlecode.com/. PMID:25675341

  13. Clonal structure affects the assembling behavior in the Japanese queenless ant Pristomyrmex punctatus

    NASA Astrophysics Data System (ADS)

    Nishide, Yudai; Satoh, Toshiyuki; Hiraoka, Tuyosi; Obara, Yoshiaki; Iwabuchi, Kikuo

    2007-10-01

    The queenless ant Pristomyrmex punctatus (Hymenoptera: Myrmicinae) has a unique society that differs from those of other typical ants. This species does not have a queen, and the workers lay eggs and produce their clones parthenogenetically. However, a colony of these ants does not always comprise members derived from a single clonal line. In this study, we examined whether P. punctatus changes its “assembling behavior” based on colony genetic structure. We prepared two subcolonies—a larger one comprising 200 individuals and a smaller one comprising 100 individuals; these subcolonies were established from a single stock colony. We investigated whether these subcolonies assemble into a single nest. The genetically monomorphic subcolonies (single clonal line) always fused into a single nest; however, the genetically polymorphic subcolonies (multiple clonal lines) did not tend to form a single colony. The present study is the first to demonstrate that the colony genetic structure significantly affects social viscosity in social insects.

  14. Punctuated Copy Number Evolution and Clonal Stasis in Triple-Negative Breast Cancer

    PubMed Central

    Gao, Ruli; Davis, Alexander; McDonald, Thomas O.; Sei, Emi; Shi, Xiuqing; Wang, Yong; Tsai, Pei-Ching; Casasent, Anna; Waters, Jill; Zhang, Hong; Meric-Bernstam, Funda; Michor, Franziska; Navin, Nicholas E.

    2016-01-01

    Aneuploidy is a hallmark of breast cancer; however, our knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study we developed a highly multiplexed single-nucleus-sequencing method to investigate copy number evolution in triple-negative breast cancer patients. We sequenced 1000 single cells from 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. We also identified a minor subpopulation of non-clonal cells that were classified as: 1) metastable, 2) pseudo-diploid, or 3) chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass. PMID:27526321

  15. Clonal reproduction with androgenesis and somatic recombination: the case of the ant Cardiocondyla kagutsuchi

    NASA Astrophysics Data System (ADS)

    Okita, Ichiro; Tsuchida, Koji

    2016-04-01

    In haplodiploid insects such as ants, male sexuals develop from unfertilised haploid eggs, while female sexuals and workers develop from fertilized diploid eggs. However, some ant species do not exchange their gene pool between sexes; both male and female sexuals are clonally produced, while workers are sexually produced. To date, three ant species, Wasmannia auropunctata, Vollenhovia emeryi, and Paratrechina longicornis, have been reported to reproduce using such reproductive systems. In this study, we reveal that in one lineage of the ant Cardiocondyla kagutsuchi, male and female sexuals are also clonally produced. In contrast to the abovementioned three species, the workers were not only sexually produced but had recombinant sequences in their nuclear internal transcribed spacer regions, although the recombinant sequences were not detected in male or female sexuals. These results suggest that the lineage likely possesses a mechanism to compensate for the reduction in genetic variation due to clonal reproduction with somatic recombination that occurs within the workers.

  16. Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

    PubMed

    Simonetti, Francesco R; Sobolewski, Michele D; Fyne, Elizabeth; Shao, Wei; Spindler, Jonathan; Hattori, Junko; Anderson, Elizabeth M; Watters, Sarah A; Hill, Shawn; Wu, Xiaolin; Wells, David; Su, Li; Luke, Brian T; Halvas, Elias K; Besson, Guillaume; Penrose, Kerri J; Yang, Zhiming; Kwan, Richard W; Van Waes, Carter; Uldrick, Thomas; Citrin, Deborah E; Kovacs, Joseph; Polis, Michael A; Rehm, Catherine A; Gorelick, Robert; Piatak, Michael; Keele, Brandon F; Kearney, Mary F; Coffin, John M; Hughes, Stephen H; Mellors, John W; Maldarelli, Frank

    2016-02-16

    Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.

  17. Intraspecific competition and light effect on reproduction of Ligularia virgaurea, an invasive native alpine grassland clonal herb.

    PubMed

    Xie, Tian-Peng; Zhang, Ge-Fei; Zhao, Zhi-Gang; Du, Guo-Zhen; He, Gui-Yong

    2014-03-01

    The relationship between sexual reproduction and clonal growth in clonal plants often shows up at the ramet level. However, only a few studies focus on the relationship at the genet level, which could finally account for evolution. The sexual reproduction and clonal growth of Ligularia virgaurea, a perennial herb widely distributed in the alpine grasslands of the Qinghai-Tibetan Plateau of China, were studied under different competition intensities and light conditions at the genet level through a potted experiment. The results showed that: (1) sexual reproduction did not depend on density or light, and increasing clonal growth with decreasing density and increasing light intensity indicated that intraspecific competition and light intensity may affect the clonal life history of L. virgaurea; (2) both sexual reproduction and clonal growth show a positive linear relationship with genet size under different densities and light conditions; (3) a threshold size is required for sexual reproduction and no evidence of a threshold size for clonal growth under different densities and light conditions; (4) light level affected the allocation of total biomass to clonal and sexual structures, with less allocation to clonal structures and more allocation to sexual structures in full sunlight than in shade; (5) light determined the onset of sexual reproduction, and the genets in the shade required a smaller threshold size for sexual reproduction to occur than the plants in full sunlight; and (6) no evidence was found of trade-offs between clonal growth and sexual reproduction under different densities and light conditions at the genet level, and the positive correlation between two reproductive modes indicated that these are two integrated processes. Clonal growth in this species may be viewed as a growth strategy that tends to maximize genet fitness.

  18. Parallel Debugging Using Graphical Views

    DTIC Science & Technology

    1988-03-01

    Voyeur , a prototype system for creating graphical views of parallel programs, provid(s a cost-effective way to construct such views for any parallel...programming system. We illustrate Voyeur by discussing four views created for debugging Poker programs. One is a vteneral trace facility for any Poker...Graphical views are essential for debugging parallel programs because of the large quan- tity of state information contained in parallel programs. Voyeur

  19. Parallel Pascal - An extended Pascal for parallel computers

    NASA Technical Reports Server (NTRS)

    Reeves, A. P.

    1984-01-01

    Parallel Pascal is an extended version of the conventional serial Pascal programming language which includes a convenient syntax for specifying array operations. It is upward compatible with standard Pascal and involves only a small number of carefully chosen new features. Parallel Pascal was developed to reduce the semantic gap between standard Pascal and a large range of highly parallel computers. Two important design goals of Parallel Pascal were efficiency and portability. Portability is particularly difficult to achieve since different parallel computers frequently have very different capabilities.

  20. Model Based Analysis of Clonal Developments Allows for Early Detection of Monoclonal Conversion and Leukemia

    PubMed Central

    Thielecke, Lars; Glauche, Ingmar

    2016-01-01

    The availability of several methods to unambiguously mark individual cells has strongly fostered the understanding of clonal developments in hematopoiesis and other stem cell driven regenerative tissues. While cellular barcoding is the method of choice for experimental studies, patients that underwent gene therapy carry a unique insertional mark within the transplanted cells originating from the integration of the retroviral vector. Close monitoring of such patients allows accessing their clonal dynamics, however, the early detection of events that predict monoclonal conversion and potentially the onset of leukemia are beneficial for treatment. We developed a simple mathematical model of a self-stabilizing hematopoietic stem cell population to generate a wide range of possible clonal developments, reproducing typical, experimentally and clinically observed scenarios. We use the resulting model scenarios to suggest and test a set of statistical measures that should allow for an interpretation and classification of relevant clonal dynamics. Apart from the assessment of several established diversity indices we suggest a measure that quantifies the extension to which the increase in the size of one clone is attributed to the total loss in the size of all other clones. By evaluating the change in relative clone sizes between consecutive measurements, the suggested measure, referred to as maximum relative clonal expansion (mRCE), proves to be highly sensitive in the detection of rapidly expanding cell clones prior to their dominant manifestation. This predictive potential places the mRCE as a suitable means for the early recognition of leukemogenesis especially in gene therapy patients that are closely monitored. Our model based approach illustrates how simulation studies can actively support the design and evaluation of preclinical strategies for the analysis and risk evaluation of clonal developments. PMID:27764218

  1. CSM parallel structural methods research

    NASA Technical Reports Server (NTRS)

    Storaasli, Olaf O.

    1989-01-01

    Parallel structural methods, research team activities, advanced architecture computers for parallel computational structural mechanics (CSM) research, the FLEX/32 multicomputer, a parallel structural analyses testbed, blade-stiffened aluminum panel with a circular cutout and the dynamic characteristics of a 60 meter, 54-bay, 3-longeron deployable truss beam are among the topics discussed.

  2. Roo: A parallel theorem prover

    SciTech Connect

    Lusk, E.L.; McCune, W.W.; Slaney, J.K.

    1991-11-01

    We describe a parallel theorem prover based on the Argonne theorem-proving system OTTER. The parallel system, called Roo, runs on shared-memory multiprocessors such as the Sequent Symmetry. We explain the parallel algorithm used and give performance results that demonstrate near-linear speedups on large problems.

  3. Parallel Eclipse Project Checkout

    NASA Technical Reports Server (NTRS)

    Crockett, Thomas M.; Joswig, Joseph C.; Shams, Khawaja S.; Powell, Mark W.; Bachmann, Andrew G.

    2011-01-01

    Parallel Eclipse Project Checkout (PEPC) is a program written to leverage parallelism and to automate the checkout process of plug-ins created in Eclipse RCP (Rich Client Platform). Eclipse plug-ins can be aggregated in a feature project. This innovation digests a feature description (xml file) and automatically checks out all of the plug-ins listed in the feature. This resolves the issue of manually checking out each plug-in required to work on the project. To minimize the amount of time necessary to checkout the plug-ins, this program makes the plug-in checkouts parallel. After parsing the feature, a request to checkout for each plug-in in the feature has been inserted. These requests are handled by a thread pool with a configurable number of threads. By checking out the plug-ins in parallel, the checkout process is streamlined before getting started on the project. For instance, projects that took 30 minutes to checkout now take less than 5 minutes. The effect is especially clear on a Mac, which has a network monitor displaying the bandwidth use. When running the client from a developer s home, the checkout process now saturates the bandwidth in order to get all the plug-ins checked out as fast as possible. For comparison, a checkout process that ranged from 8-200 Kbps from a developer s home is now able to saturate a pipe of 1.3 Mbps, resulting in significantly faster checkouts. Eclipse IDE (integrated development environment) tries to build a project as soon as it is downloaded. As part of another optimization, this innovation programmatically tells Eclipse to stop building while checkouts are happening, which dramatically reduces lock contention and enables plug-ins to continue downloading until all of them finish. Furthermore, the software re-enables automatic building, and forces Eclipse to do a clean build once it finishes checking out all of the plug-ins. This software is fully generic and does not contain any NASA-specific code. It can be applied to any

  4. Parallel sphere rendering

    SciTech Connect

    Krogh, M.; Hansen, C.; Painter, J.; de Verdiere, G.C.

    1995-05-01

    Sphere rendering is an important method for visualizing molecular dynamics data. This paper presents a parallel divide-and-conquer algorithm that is almost 90 times faster than current graphics workstations. To render extremely large data sets and large images, the algorithm uses the MIMD features of the supercomputers to divide up the data, render independent partial images, and then finally composite the multiple partial images using an optimal method. The algorithm and performance results are presented for the CM-5 and the T3D.

  5. Parallelized direct execution simulation of message-passing parallel programs

    NASA Technical Reports Server (NTRS)

    Dickens, Phillip M.; Heidelberger, Philip; Nicol, David M.

    1994-01-01

    As massively parallel computers proliferate, there is growing interest in findings ways by which performance of massively parallel codes can be efficiently predicted. This problem arises in diverse contexts such as parallelizing computers, parallel performance monitoring, and parallel algorithm development. In this paper we describe one solution where one directly executes the application code, but uses a discrete-event simulator to model details of the presumed parallel machine such as operating system and communication network behavior. Because this approach is computationally expensive, we are interested in its own parallelization specifically the parallelization of the discrete-event simulator. We describe methods suitable for parallelized direct execution simulation of message-passing parallel programs, and report on the performance of such a system, Large Application Parallel Simulation Environment (LAPSE), we have built on the Intel Paragon. On all codes measured to date, LAPSE predicts performance well typically within 10 percent relative error. Depending on the nature of the application code, we have observed low slowdowns (relative to natively executing code) and high relative speedups using up to 64 processors.

  6. Tc1 clonal T cell expansion during chronic graft-versus-host disease-associated hypereosinophilia.

    PubMed

    Clave, Emmanuel; Xhaard, Aliénor; Douay, Corrine; Adès, Lionel; Cayuela, Jean Michel; Peffault de Latour, Régis; Robin, Marie; Toubert, Antoine; Socié, Gérard

    2014-05-01

    Although hypereosinophilia (HE) associated with chronic graft-versus-host disease (GVHD) has long been recognized, biological data on this phenomenon are scarce. Here we compare patients with chronic GVHD with HE together with a clonal T cell expansion and control patients with acute or chronic GVHD but without HE. These clonal expansions share a CD8(+) TC1 phenotype rather than a CD4(+) Th2 profile. In contrast to the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, these allogeneic CD8(+) clones do not recognize the epitopes of herpesviruses. Furthermore, these TC1 clones do not produce IL-17 as described in the DRESS syndrome.

  7. The two-mutant problem: clonal interference in evolutionary graph theory.

    PubMed

    Paley, Chris; Taraskin, Sergei; Elliott, Stephen

    2010-10-01

    In large asexual populations, clonal interference, whereby different beneficial mutations compete to fix in the population simultaneously, may be the norm. Results extrapolated from the spread of individual mutations in homogeneous backgrounds are found to be misleading in such situations: clonal interference severely inhibits the spread of beneficial mutations. In contrast with results gained in systems with just one mutation striving for fixation at any one time, the spatial structure of the population is found to be an important factor in determining the fixation probability when there are two beneficial mutations.

  8. Preponderance of clonality triggers loss of sex in Bulbophyllum bicolor, an obligately outcrossing epiphytic orchid.

    PubMed

    Hu, Ai-Qun; Gale, Stephan W; Kumar, Pankaj; Saunders, Richard M K; Sun, Mei; Fischer, Gunter A

    2017-04-08

    Vegetative propagation (clonal growth) conveys several evolutionary advantages that positively affect life history fitness and is a widespread phenomenon among angiosperms that also reproduce sexually. However, a bias towards clonality can interfere with sexual reproduction and lead to sexual extinction, although a dearth of effective genetic tools and mathematical models for clonal plants has hampered assessment of these impacts. Using the endangered tropical epiphytic or lithophytic orchid Bulbophyllum bicolor as a model, we integrated an examination of breeding system with 12 microsatellite loci and models valid for clonal species to test for the 'loss of sex' and infer likely consequences for long-term reproductive dynamics. Bagging experiments and field observations revealed B. bicolor to be self-incompatible and pollinator-dependent, with an absence of fruit-set over four years. Challenging the assumptions that clonal populations can be as genotypically diverse as sexually reproducing ones and that clonality does not greatly influence genetic structure, just 22 multilocus genotypes were confirmed among all 15 extant natural populations, 12 of the populations were found to be monoclonal and all three multiclonal ones exhibited a distinct phalanx clonal architecture. Our results suggest that all B. bicolor populations depend overwhelmingly on clonal growth for persistence, with a concomitant loss of sex due to an absence of pollinators and a lack of mating opportunities at virtually all sites, both of which are further entrenched by habitat fragmentation. Such cryptic life history impacts, potentially contributing to extinction debt, could be widespread among similarly fragmented, outcrossing tropical epiphytes, demanding urgent conservation attention. This article is protected by copyright. All rights reserved.

  9. 20q- clonality in a case of oral sweet syndrome and myelodysplasia.

    PubMed

    Van Loon, Katherine; Gill, Ryan M; McMahon, Patrick; Chigurupati, Radhika; Siddiqi, Imran; Fox, Lindy; Damon, Lloyd; McCalmont, Timothy H; Jordan, Richard; Wolf, Jeffrey

    2012-02-01

    We report the case of a patient with myelodysplasia who had Sweet syndrome of the oral cavity. An atypical myeloid immunophenotype was present in the gingival biopsy specimen and in a concurrent bone marrow specimen. Fluorescence in situ hybridization performed on the gingival biopsy specimen demonstrated the same del(20q) cytogenetic abnormality present in the bone marrow, confirming the presence of a clonally related myeloid proliferation in both tissues. This is the first reported case of Sweet syndrome and myelodysplasia in which the chromosomal abnormality was identified in the neutrophilic infiltrate, confirming the neutrophilic infiltrate to be clonally related to the underlying myeloid neoplasm.

  10. Age-related EBV positive clonal B-cell Lymphoid proliferation (EBV+-DLBCL)

    PubMed Central

    Doukas-Alexiou, Marina; Stoufi, Eleana; Kittas, Christos; Pangalis, Gerasimos; Laskaris, George

    2017-01-01

    The Ebstein Barr virus(EBV), herpes virus 5 has been associated with lymphoproliferative disordrers. Age-related EBV+ B-LPD is defined as an EBV+ clonal B-cell lymphoid proliferation or EBV+-DLBCL developing in patients over the age of 40 years in the absence of any known immunodeficiency and without an underlying T-cell lymphoma1. We present a case of EBV+ clonal B-cell lymphoid proliferation. Key words:Oral mucosa ulcer, EBV+-DLBCL, age related. PMID:28149483

  11. Synchrony of clonal cell proliferation and contiguity of clonally related cells: production of mosaicism in the ventricular zone of developing mouse neocortex

    NASA Technical Reports Server (NTRS)

    Cai, L.; Hayes, N. L.; Nowakowski, R. S.

    1997-01-01

    We have analyzed clonal cell proliferation in the ventricular zone (VZ) of the early developing mouse neocortex with a replication-incompetent retrovirus encoding human placental alkaline phosphatase (AP). The retrovirus was injected into the lateral ventricles on embryonic day 11 (E11), i.e., at the onset of neuronogenesis. Three days postinjection, on E14, a total of 259 AP-labeled clones of various sizes were found in 7 fetal brains. There are approximately 7 cell cycles between E11 and E14 (), and there is a 1-2 cell cycle delay between retroviral injection and the production of a retrovirally labeled "founder" cell; thus, we estimate that the "age" of the clones was about 5-6 cell cycles. Almost one-half of the clones (48.3%) identified were pure proliferating clones containing cells only in the VZ. Another 18.5% contained both proliferating and postproliferative cells, and 33.2% contained only postproliferative cells. It was striking that over 90% of the clonally related proliferating cells occurred in clusters of two or more apparently contiguous cells, and about 73% of the proliferating cells occurred in clusters of three or more cells. Regardless of the number of cells in the clone, these clusters were tightly packed and confined to a single level of the VZ. This clustering of proliferating cells indicates that clonally related cells maintain neighbor-neighbor relationships as they undergo interkinetic nuclear migration and progress through several cell cycles, and, as a result, the ventricular zone is a mosaic of small clusters of clonally related and synchronously cycling cells. In addition, cells in the intermediate zone and the cortical plate were also frequently clustered, indicating that they became postproliferative at a similar time and that the output of the VZ is influenced by its mosaic structure.

  12. Parallelizing quantum circuit synthesis

    NASA Astrophysics Data System (ADS)

    Di Matteo, Olivia; Mosca, Michele

    2016-03-01

    Quantum circuit synthesis is the process in which an arbitrary unitary operation is decomposed into a sequence of gates from a universal set, typically one which a quantum computer can implement both efficiently and fault-tolerantly. As physical implementations of quantum computers improve, the need is growing for tools that can effectively synthesize components of the circuits and algorithms they will run. Existing algorithms for exact, multi-qubit circuit synthesis scale exponentially in the number of qubits and circuit depth, leaving synthesis intractable for circuits on more than a handful of qubits. Even modest improvements in circuit synthesis procedures may lead to significant advances, pushing forward the boundaries of not only the size of solvable circuit synthesis problems, but also in what can be realized physically as a result of having more efficient circuits. We present a method for quantum circuit synthesis using deterministic walks. Also termed pseudorandom walks, these are walks in which once a starting point is chosen, its path is completely determined. We apply our method to construct a parallel framework for circuit synthesis, and implement one such version performing optimal T-count synthesis over the Clifford+T gate set. We use our software to present examples where parallelization offers a significant speedup on the runtime, as well as directly confirm that the 4-qubit 1-bit full adder has optimal T-count 7 and T-depth 3.

  13. Parallel ptychographic reconstruction

    PubMed Central

    Nashed, Youssef S. G.; Vine, David J.; Peterka, Tom; Deng, Junjing; Ross, Rob; Jacobsen, Chris

    2014-01-01

    Ptychography is an imaging method whereby a coherent beam is scanned across an object, and an image is obtained by iterative phasing of the set of diffraction patterns. It is able to be used to image extended objects at a resolution limited by scattering strength of the object and detector geometry, rather than at an optics-imposed limit. As technical advances allow larger fields to be imaged, computational challenges arise for reconstructing the correspondingly larger data volumes, yet at the same time there is also a need to deliver reconstructed images immediately so that one can evaluate the next steps to take in an experiment. Here we present a parallel method for real-time ptychographic phase retrieval. It uses a hybrid parallel strategy to divide the computation between multiple graphics processing units (GPUs) and then employs novel techniques to merge sub-datasets into a single complex phase and amplitude image. Results are shown on a simulated specimen and a real dataset from an X-ray experiment conducted at a synchrotron light source. PMID:25607174

  14. Tolerant (parallel) Programming

    NASA Technical Reports Server (NTRS)

    DiNucci, David C.; Bailey, David H. (Technical Monitor)

    1997-01-01

    In order to be truly portable, a program must be tolerant of a wide range of development and execution environments, and a parallel program is just one which must be tolerant of a very wide range. This paper first defines the term "tolerant programming", then describes many layers of tools to accomplish it. The primary focus is on F-Nets, a formal model for expressing computation as a folded partial-ordering of operations, thereby providing an architecture-independent expression of tolerant parallel algorithms. For implementing F-Nets, Cooperative Data Sharing (CDS) is a subroutine package for implementing communication efficiently in a large number of environments (e.g. shared memory and message passing). Software Cabling (SC), a very-high-level graphical programming language for building large F-Nets, possesses many of the features normally expected from today's computer languages (e.g. data abstraction, array operations). Finally, L2(sup 3) is a CASE tool which facilitates the construction, compilation, execution, and debugging of SC programs.

  15. Applied Parallel Metadata Indexing

    SciTech Connect

    Jacobi, Michael R

    2012-08-01

    The GPFS Archive is parallel archive is a parallel archive used by hundreds of users in the Turquoise collaboration network. It houses 4+ petabytes of data in more than 170 million files. Currently, users must navigate the file system to retrieve their data, requiring them to remember file paths and names. A better solution might allow users to tag data with meaningful labels and searach the archive using standard and user-defined metadata, while maintaining security. last summer, I developed the backend to a tool that adheres to these design goals. The backend works by importing GPFS metadata into a MongoDB cluster, which is then indexed on each attribute. This summer, the author implemented security and developed the user interfae for the search tool. To meet security requirements, each database table is associated with a single user, which only stores records that the user may read, and requires a set of credentials to access. The interface to the search tool is implemented using FUSE (Filesystem in USErspace). FUSE is an intermediate layer that intercepts file system calls and allows the developer to redefine how those calls behave. In the case of this tool, FUSE interfaces with MongoDB to issue queries and populate output. A FUSE implementation is desirable because it allows users to interact with the search tool using commands they are already familiar with. These security and interface additions are essential for a usable product.

  16. A systolic array parallelizing compiler

    SciTech Connect

    Tseng, P.S. )

    1990-01-01

    This book presents a completely new approach to the problem of systolic array parallelizing compiler. It describes the AL parallelizing compiler for the Warp systolic array, the first working systolic array parallelizing compiler which can generate efficient parallel code for complete LINPACK routines. This book begins by analyzing the architectural strength of the Warp systolic array. It proposes a model for mapping programs onto the machine and introduces the notion of data relations for optimizing the program mapping. Also presented are successful applications of the AL compiler in matrix computation and image processing. A complete listing of the source program and compiler-generated parallel code are given to clarify the overall picture of the compiler. The book concludes that systolic array parallelizing compiler can produce efficient parallel code, almost identical to what the user would have written by hand.

  17. Systematic Survey of Clonal Complexity in Tuberculosis at a Populational Level and Detailed Characterization of the Isolates Involved ▿

    PubMed Central

    Navarro, Yurena; Herranz, Marta; Pérez-Lago, Laura; Martínez Lirola, Miguel; Ruiz-Serrano, Maria Jesús; Bouza, Emilio; García de Viedma, Darío

    2011-01-01

    Clonally complex infections by Mycobacterium tuberculosis are progressively more accepted. Studies of their dimension in epidemiological scenarios where the infective pressure is not high are scarce. Our study systematically searched for clonally complex infections (mixed infections by more than one strain and simultaneous presence of clonal variants) by applying mycobacterial interspersed repetitive-unit (MIRU)–variable-number tandem-repeat (VNTR) analysis to M. tuberculosis isolates from two population-based samples of respiratory (703 cases) and respiratory-extrapulmonary (R+E) tuberculosis (TB) cases (71 cases) in a context of moderate TB incidence. Clonally complex infections were found in 11 (1.6%) of the respiratory TB cases and in 10 (14.1%) of those with R+E TB. Among the 21 cases with clonally complex TB, 9 were infected by 2 independent strains and the remaining 12 showed the simultaneous presence of 2 to 3 clonal variants. For the 10 R+E TB cases with clonally complex infections, compartmentalization (different compositions of strains/clonal variants in independent infected sites) was found in 9 of them. All the strains/clonal variants were also genotyped by IS6110-based restriction fragment length polymorphism analysis, which split two MIRU-defined clonal variants, although in general, it showed a lower discriminatory power to identify the clonal heterogeneity revealed by MIRU-VNTR analysis. The comparative analysis of IS6110 insertion sites between coinfecting clonal variants showed differences in the genes coding for a cutinase, a PPE family protein, and two conserved hypothetical proteins. Diagnostic delay, existence of previous TB, risk for overexposure, and clustered/orphan status of the involved strains were analyzed to propose possible explanations for the cases with clonally complex infections. Our study characterizes in detail all the clonally complex infections by M. tuberculosis found in a systematic survey and contributes to the

  18. Parallel Computing in SCALE

    SciTech Connect

    DeHart, Mark D; Williams, Mark L; Bowman, Stephen M

    2010-01-01

    The SCALE computational architecture has remained basically the same since its inception 30 years ago, although constituent modules and capabilities have changed significantly. This SCALE concept was intended to provide a framework whereby independent codes can be linked to provide a more comprehensive capability than possible with the individual programs - allowing flexibility to address a wide variety of applications. However, the current system was designed originally for mainframe computers with a single CPU and with significantly less memory than today's personal computers. It has been recognized that the present SCALE computation system could be restructured to take advantage of modern hardware and software capabilities, while retaining many of the modular features of the present system. Preliminary work is being done to define specifications and capabilities for a more advanced computational architecture. This paper describes the state of current SCALE development activities and plans for future development. With the release of SCALE 6.1 in 2010, a new phase of evolutionary development will be available to SCALE users within the TRITON and NEWT modules. The SCALE (Standardized Computer Analyses for Licensing Evaluation) code system developed by Oak Ridge National Laboratory (ORNL) provides a comprehensive and integrated package of codes and nuclear data for a wide range of applications in criticality safety, reactor physics, shielding, isotopic depletion and decay, and sensitivity/uncertainty (S/U) analysis. Over the last three years, since the release of version 5.1 in 2006, several important new codes have been introduced within SCALE, and significant advances applied to existing codes. Many of these new features became available with the release of SCALE 6.0 in early 2009. However, beginning with SCALE 6.1, a first generation of parallel computing is being introduced. In addition to near-term improvements, a plan for longer term SCALE enhancement

  19. Toward Parallel Document Clustering

    SciTech Connect

    Mogill, Jace A.; Haglin, David J.

    2011-09-01

    A key challenge to automated clustering of documents in large text corpora is the high cost of comparing documents in a multimillion dimensional document space. The Anchors Hierarchy is a fast data structure and algorithm for localizing data based on a triangle inequality obeying distance metric, the algorithm strives to minimize the number of distance calculations needed to cluster the documents into “anchors” around reference documents called “pivots”. We extend the original algorithm to increase the amount of available parallelism and consider two implementations: a complex data structure which affords efficient searching, and a simple data structure which requires repeated sorting. The sorting implementation is integrated with a text corpora “Bag of Words” program and initial performance results of end-to-end a document processing workflow are reported.

  20. Parallel Polarization State Generation

    NASA Astrophysics Data System (ADS)

    She, Alan; Capasso, Federico

    2016-05-01

    The control of polarization, an essential property of light, is of wide scientific and technological interest. The general problem of generating arbitrary time-varying states of polarization (SOP) has always been mathematically formulated by a series of linear transformations, i.e. a product of matrices, imposing a serial architecture. Here we show a parallel architecture described by a sum of matrices. The theory is experimentally demonstrated by modulating spatially-separated polarization components of a laser using a digital micromirror device that are subsequently beam combined. This method greatly expands the parameter space for engineering devices that control polarization. Consequently, performance characteristics, such as speed, stability, and spectral range, are entirely dictated by the technologies of optical intensity modulation, including absorption, reflection, emission, and scattering. This opens up important prospects for polarization state generation (PSG) with unique performance characteristics with applications in spectroscopic ellipsometry, spectropolarimetry, communications, imaging, and security.

  1. Parallel Polarization State Generation

    PubMed Central

    She, Alan; Capasso, Federico

    2016-01-01

    The control of polarization, an essential property of light, is of wide scientific and technological interest. The general problem of generating arbitrary time-varying states of polarization (SOP) has always been mathematically formulated by a series of linear transformations, i.e. a product of matrices, imposing a serial architecture. Here we show a parallel architecture described by a sum of matrices. The theory is experimentally demonstrated by modulating spatially-separated polarization components of a laser using a digital micromirror device that are subsequently beam combined. This method greatly expands the parameter space for engineering devices that control polarization. Consequently, performance characteristics, such as speed, stability, and spectral range, are entirely dictated by the technologies of optical intensity modulation, including absorption, reflection, emission, and scattering. This opens up important prospects for polarization state generation (PSG) with unique performance characteristics with applications in spectroscopic ellipsometry, spectropolarimetry, communications, imaging, and security. PMID:27184813

  2. A parallel programming environment supporting multiple data-parallel modules

    SciTech Connect

    Seevers, B.K.; Quinn, M.J. ); Hatcher, P.J. )

    1992-10-01

    We describe a system that allows programmers to take advantage of both control and data parallelism through multiple intercommunicating data-parallel modules. This programming environment extends C-type stream I/O to include intermodule communication channels. The progammer writes each module as a separate data-parallel program, then develops a channel linker specification describing how to connect the modules together. A channel linker we have developed loads the separate modules on the parallel machine and binds the communication channels together as specified. We present performance data that demonstrates a mixed control- and data-parallel solution can yield better performance than a strictly data-parallel solution. The system described currently runs on the Intel iWarp multicomputer.

  3. Parallel imaging microfluidic cytometer.

    PubMed

    Ehrlich, Daniel J; McKenna, Brian K; Evans, James G; Belkina, Anna C; Denis, Gerald V; Sherr, David H; Cheung, Man Ching

    2011-01-01

    By adding an additional degree of freedom from multichannel flow, the parallel microfluidic cytometer (PMC) combines some of the best features of fluorescence-activated flow cytometry (FCM) and microscope-based high-content screening (HCS). The PMC (i) lends itself to fast processing of large numbers of samples, (ii) adds a 1D imaging capability for intracellular localization assays (HCS), (iii) has a high rare-cell sensitivity, and (iv) has an unusual capability for time-synchronized sampling. An inability to practically handle large sample numbers has restricted applications of conventional flow cytometers and microscopes in combinatorial cell assays, network biology, and drug discovery. The PMC promises to relieve a bottleneck in these previously constrained applications. The PMC may also be a powerful tool for finding rare primary cells in the clinic. The multichannel architecture of current PMC prototypes allows 384 unique samples for a cell-based screen to be read out in ∼6-10 min, about 30 times the speed of most current FCM systems. In 1D intracellular imaging, the PMC can obtain protein localization using HCS marker strategies at many times for the sample throughput of charge-coupled device (CCD)-based microscopes or CCD-based single-channel flow cytometers. The PMC also permits the signal integration time to be varied over a larger range than is practical in conventional flow cytometers. The signal-to-noise advantages are useful, for example, in counting rare positive cells in the most difficult early stages of genome-wide screening. We review the status of parallel microfluidic cytometry and discuss some of the directions the new technology may take.

  4. Intratumor diversity and clonal evolution in cancer--a skeptical standpoint.

    PubMed

    Gisselsson, David

    2011-01-01

    Clonal evolution in cancer is intimately linked to the concept of intratumor cellular diversity, as the latter is a prerequisite for Darwinian selection at the micro-level. It has been frequently suggested in the literature that clonal evolution can be promoted by an elevated rate of mutation in tumor cells, so-called genomic instability, the mechanisms of which are now becoming increasingly well characterized. However, several issues need clarification before the presumably complex relationship between mutation rate, intratumor diversity, and clonal evolution can be understood sufficiently well to translate into models that predict the course of tumor disease. In particular, it has to be clarified which of the proposed mechanisms for genomic instability that are able to generate daughter cells with sufficient viability to form novel clones, how clones with different genomic changes differ phenotypically from each other, and what the selective forces are that guide competition among diverse clones in different microenvironments. Furthermore, standardized measurements of mutation rates at the chromosome level, as well as genotypic and phenotypic diversity, are essential to compare data from different studies. Finally, the relationship between clonal variation brought about by genomic instability, on the one hand, and cellular differentiation hierarchies, on the other hand, should be explored to put genomic instability in the context of the tumor stem cell hypothesis.

  5. OCCURRENCE OF ANTIBIOTIC-RESISTANT UROPATHOGENIC ESCHERICHIA COLI CLONAL GROUP A IN WASTEWATER EFFLUENTS

    EPA Science Inventory

    Isolates of Escherichia coli belonging to clonal group A (CGA), a recently described disseminated cause of drug-resistant urinary tract infections in humans, were present in four of seven sewage effluents collected from geographically dispersed areas of the United States. ...

  6. Measuring genetic diversity and purity of cranberry clonal cultivars using microsatellite markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cranberries (Vaccinium macrocarpon Ait.) are an economically important fruit crop in North America, which are grown from clonally preserved and propagated cultivars. Growers usually select cultivars for their operation based on the know attributes of each cultivar in order to best fit their particul...

  7. Analyzing clonal fidelity of micropropagated Psidium guajava L. plants using simple sequence repeat markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Micropropagation of Psidium guajava L. (guava) is a viable alternative to currently adopted techniques for large-scale plant propagation of commercial cultivars. Assessment of clonal fidelity in micropropagated plants is the first step towards ensuring genetic uniformity in mass production of planti...

  8. Current Approaches and Future Perspectives for In Vivo Clonal Tracking of Hematopoietic Cells.

    PubMed

    Scala, Serena; Leonardelli, Lorena; Biasco, Luca

    2016-01-01

    Over the past years, clonal tracking has gained the center stage as a unique technology capable to unveil population dynamics and hierarchical relationships in vivo. We here highlighted the main open questions related to the in vivo clonal behavior of hematopoietic cells with a particular focus on hematopoietic stem and progenitor cells and T cells as main targets of cell- and gene-therapies. We walked through the current methods applied for tracing in vivo dynamics and functions of hematopoietic cells in animal models and we described the results of early studies conducted on humans. We specifically focused our attention on the recent use of retroviral/lentiviral vector Integration Site (IS) analyses to follow stably marked clones and their progeny in vivo. We showed how this molecular tracking method can be successfully employed in human studies to unveil the clonal behavior of hematopoietic cells, describing pioneering works conducted on samples from gene therapy treated patients. Clonal tracking through IS identification still comes with a complex wet-experimental protocol and technical/analytical constraints. In this regard, we reviewed the features of the available computational tools for the identification and quantification of ISs and we highlighted the potential future improvements of IS-based tracking, as this technology is becoming a major source of information on in vivo fate and survival of engineered cells in humans.

  9. A simple model for the influence of habitat resource availability on lateral clonal spread

    PubMed Central

    Weiser, Martin; Smyčka, Jan

    2015-01-01

    Plant clonal spread is ubiquitous and of great interest, owing both to its key role in plant community assembly and its suitability for plant behaviour research. However, mechanisms that govern spreading distance are not well known. Here we link spacer costs and below-ground competition in a simple model of growth in a homogeneous below-ground environment, in which optimal distance between ramets is based on minimizing the sum of these costs. Using this model, we predict a high prevalence of clonal growth that does not employ spacers in resource-poor environments and a nonlinear increase in spreading distance in response to increasing below-ground resource availability. Analysis of database data on clonal growth in relationship to below-ground resource availability revealed that patterns of the spread based on stolons is compatible with the model's predictions. As expected, model prediction failed for rhizomatous species, where spacer sizes are likely to be selected mainly to play roles other than spread. The model's simplicity makes it useful as a null model in testing hypotheses about the effects of environmental heterogeneity on clonal spread. PMID:25833862

  10. Clonality and micro-diversity of a nationwide spreading genotype of Mycobacterium tuberculosis in Japan.

    PubMed

    Wada, Takayuki; Iwamoto, Tomotada; Tamaru, Aki; Seto, Junji; Ahiko, Tadayuki; Yamamoto, Kaori; Hase, Atushi; Maeda, Shinji; Yamamoto, Taro

    2015-01-01

    Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as 'M-strain' has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypic markers will be an efficient strategy for the big data in various settings for public health actions against TB.

  11. Clonal population structures are derived from various population processes in the protistan oyster parasite Perkinsus marinus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Population genetic analysis of genotypes comprised of seven microsatellite loci revealed clonal genetic patterns in each of four populations of the protistan estuarine parasite Perkinsus marinus. Each locus was amplified directly from DNA extracted from infected oysters collected from four geographi...

  12. Vigor rating and brix for first clonal selection stage of the Canal Point Cultivar Development Program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A better understanding of sugarcane (Saccharum spp.) genetic variability in agronomic performance will help optimize breeding and selection strategies. Vigor ratings and Brix data were collected from the 2009 and 2010 clones in the first clonal selection stage (Stage I) of the Canal Point (CP) sugar...

  13. Identification of genomic clonal types of Actinobacillus actinomycetemcomitans by restriction endonuclease analysis.

    PubMed Central

    Han, N; Hoover, C I; Winkler, J R; Ng, C Y; Armitage, G C

    1991-01-01

    To evaluate its utility in discriminating different strains, restriction endonuclease analysis was applied to 12 strains of Actinobacillus actinomycetemcomitans (3 serotype a, 5 serotype b, and 4 serotype c strains). DNA isolated from each strain was digested by 12 different restriction endonucleases, and the electrophoretic banding patterns of the resulting DNA fragments were compared. The DNA fragment patterns produced by SalI, XhoI, and XbaI for the 12 A. actinomycetemcomitans strains were simple (less than 30 bands) and allowed us to recognize easily 10 distinct genomic clonal types. The three serotype a strains exhibited distinctly different clonal types from one another, the five serotype b strains exhibited an additional four distinct clonal types, and the four serotype c strains showed another three different clonal types. The other endonucleases tested were less useful in typing A. actinomycetemcomitans. We conclude that restriction endonuclease analysis is a powerful tool for typing and discerning genetic heterogeneity and homogeneity among A. actinomycetemcomitans strains. It should, therefore, be very useful for epidemiologic studies. Images PMID:1761677

  14. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    PubMed

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  15. Detectable clonal mosaicism from birth to old age and its relationship to cancer

    PubMed Central

    Laurie, Cathy C.; Laurie, Cecelia A.; Rice, Kenneth; Doheny, Kimberly F.; Zelnick, Leila R.; McHugh, Caitlin P.; Ling, Hua; Hetrick, Kurt N.; Pugh, Elizabeth W.; Amos, Chris; Wei, Qingyi; Wang, Li-e; Lee, Jeffrey E.; Barnes, Kathleen C.; Hansel, Nadia N.; Mathias, Rasika; Daley, Denise; Beaty, Terri H.; Scott, Alan F.; Ruczinski, Ingo; Scharpf, Rob B.; Bierut, Laura J.; Hartz, Sarah M.; Landi, Maria Teresa; Freedman, Neal D.; Goldin, Lynn R.; Ginsburg, David; Li, Jun; Desch, Karl C.; Strom, Sara S.; Blot, William J.; Signorello, Lisa B.; Ingles, Sue A.; Chanock, Stephen J.; Berndt, Sonja I.; Le Marchand, Loic; Henderson, Brian E.; Monroe, Kristine R; Heit, John A.; de Andrade, Mariza; Armasu, Sebastian M.; Regnier, Cynthia; Lowe, William L.; Hayes, M. Geoffrey; Marazita, Mary L.; Feingold, Eleanor; Murray, Jeffrey C.; Melbye, Mads; Feenstra, Bjarke; Kang, Jae H.; Wiggs, Janey L.; Jarvik, Gail P.; McDavid, Andrew N.; Seshan, Venkatraman E.; Mirel, Daniel B.; Crenshaw, Andrew; Sharopova, Nataliya; Wise, Anastasia; Shen, Jess; Crosslin, David R.; Levine, David M.; Zheng, Xiuwen; Udren, Jenna I; Bennett, Siiri; Nelson, Sarah C.; Gogarten, Stephanie M.; Conomos, Matthew P.; Heagerty, Patrick; Manolio, Teri; Pasquale, Louis R.; Haiman, Christopher A.; Caporaso, Neil; Weir, Bruce S.

    2012-01-01

    Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rises rapidly to 2–3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions that pinpoint the locations of genes previously associated with hematological cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer prior to DNA sampling, those without a prior diagnosis have an estimated 10-fold higher risk of a subsequent hematological cancer (95% confidence interval = 6–18). PMID:22561516

  16. Clonality and serotypes of Streptococcus mutans among children by multilocus sequence typing

    PubMed Central

    Momeni, Stephanie S.; Whiddon, Jennifer; Cheon, Kyounga; Moser, Stephen A.; Childers, Noel K.

    2015-01-01

    Studies using multilocus sequence typing (MLST) have demonstrated that Streptococcus mutans isolates are genetically diverse. Our laboratory previously demonstrated clonality of S. mutans using MLST but could not discount the possibility of sampling bias. In this study, the clonality of randomly selected S. mutans plaque isolates from African American children was examined using MLST. Serotype and presence of collagen-binding proteins (CBP) cnm/cbm were also assessed. One hundred S. mutans isolates were randomly selected for MLST analysis. Sequence analysis was performed and phylogenetic trees were generated using START2 and MEGA. Thirty-four sequence types (ST) were identified of which 27 were unique to this population. Seventy-five percent of the isolates clustered into 16 clonal groups. Serotypes observed were c (n=84), e (n=3), and k (n=11). The prevalence of S. mutans isolates serotype k was notably high at 17.5%. All isolates were cnm/cbm negative. The clonality of S. mutans demonstrated in this study illustrates the importance of localized populations studies and are consistent with transmission. The prevalence of serotype k, a recently proposed systemic pathogen, observed in this study is higher than reported in most populations and is the first report of S. mutans serotype k in a US population. PMID:26443288

  17. Clonal and spatial genetic structure within populations of a coastal plant, Carex kobomugi (Cyperaceae).

    PubMed

    Ohsako, Takanori

    2010-03-01

    Clarification of clonal growth pattern is critical for understanding the population dynamics and reproductive system evolution of clonal plant species. The contribution of clonality to the spatial genetic structure (SGS) within populations is also an important issue. I examined the spatial distribution of genetic variability within two populations of the coastal plant Carex kobomugi using seven microsatellite loci. Genotyping of 226 and 140 ramets within 14 × 40 m and 14 × 34 m plots on two populations revealed 36 and 33 multilocus genotypes, respectively. To quantify the extent of intermingling among clones, for each genet, I calculated the dominance of ramets belonging to a particular genet within a spatial range of the genet. Furthermore, I analyzed spatial distribution of genotypes within 2 × 2 m and 1 × 2 m quadrats using second-order spatial statistics. These analyses indicated that clones are highly intermingled, suggesting a low level of spatial interaction among clones. Spatial autocorrelation analysis of kinship coefficient including all pairs of ramets showed significantly stronger SGS than analysis considering only pairs between different genets. I conclude that clonal propagation largely contributes to SGS at a fine scale.

  18. Clonally Expanding Thymocytes Having Lineage Capability in Gamma-Ray-Induced Mouse Atrophic Thymus

    SciTech Connect

    Yamamoto, Takashi; Morita, Shin-ichi; Go, Rieka; Obata, Miki; Katsuragi, Yoshinori; Fujita, Yukari; Maeda, Yoshitaka; Yokoyama, Minesuke; Aoyagi, Yutaka; Ichikawa, Hitoshi; Mishima, Yukio; Kominami, Ryo

    2010-05-01

    Purpose: To characterize, in the setting of gamma-ray-induced atrophic thymus, probable prelymphoma cells showing clonal growth and changes in signaling, including DNA damage checkpoint. Methods and Materials: A total of 111 and 45 mouse atrophic thymuses at 40 and 80 days, respectively, after gamma-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRbeta locus, flow cytometry for cell cycle, and Western blotting for the activation of DNA damage checkpoints. Results: Limited D-J rearrangement patterns distinct from normal thymus were detected at high frequencies (43 of 111 for 40-day thymus and 21 of 45 for 80-day thymus). Those clonally expanded thymocytes mostly consisted of CD4{sup +}CD8{sup +} double-positive cells, indicating the retention of lineage capability. They exhibited pausing at a late G1 phase of cell cycle progression but did not show the activation of DNA damage checkpoints such as gammaH2AX, Chk1/2, or p53. Of interest is that 17 of the 52 thymuses showing normal D-J rearrangement patterns at 40 days after irradiation showed allelic loss at the Bcl11b tumor suppressor locus, also indicating clonal expansion. Conclusion: The thymocytes of clonal growth detected resemble human chronic myeloid leukemia in possessing self-renewal and lineage capability, and therefore they can be a candidate of the lymphoma-initiating cells.

  19. Genetic variation in fitness within a clonal population of a plant RNA virus.

    PubMed

    Cervera, Héctor; Elena, Santiago F

    2016-01-01

    A long-standing observation in evolutionary virology is that RNA virus populations are highly polymorphic, composed by a mixture of genotypes whose abundances in the population depend on complex interaction between fitness differences, mutational coupling and genetic drift. It was shown long ago, though in cell cultures, that most of these genotypes had lower fitness than the population they belong, an observation that explained why single-virion passages turned on Muller's ratchet while very large population passages resulted in fitness increases in novel environments. Here we report the results of an experiment specifically designed to evaluate in vivo the fitness differences among the subclonal components of a clonal population of the plant RNA virus tobacco etch potyvirus (TEV). Over 100 individual biological subclones from a TEV clonal population well adapted to the natural tobacco host were obtained by infectivity assays on a local lesion host. The replicative fitness of these subclones was then evaluated during infection of tobacco relative to the fitness of large random samples taken from the starting clonal population. Fitness was evaluated at increasing number of days post-inoculation. We found that at early days, the average fitness of subclones was significantly lower than the fitness of the clonal population, thus confirming previous observations that most subclones contained deleterious mutations. However, as the number of days of viral replication increases, population size expands exponentially, more beneficial and compensatory mutations are produced, and selection becomes more effective in optimizing fitness, the differences between subclones and the population disappeared.

  20. Comparison of stem morphology and anatomy of two alfalfa clonal lines exhibiting divergent cell wall composition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In previous research, two alfalfa clonal lines (252, 1283) were identified that exhibited environmentally stable differences in stem cell walls. Compared to stems of 1283, stems of 252 have a higher cell wall concentration and greater amounts of lignin and cellulose but reduced levels of pectic suga...

  1. Reduced Inhomogeneity of Angelica acutiloba Plants Propagated Clonally Through Somatic Embryoids.

    PubMed

    Miura, Y; Fukui, H; Tabata, M

    1988-02-01

    Clonal plants propagated from a single plant of a commercial variety of ANGELICA ACUTILOBA (Umbelliferae) through somatic embryoids induced in cell suspension cultures proved to be significantly more uniform with respect to the contents of medicinally important chemical constituents (ligustilide and choline) of the root when compared with seed-propagated plants.

  2. Prevalence, serotype, virulence characteristics, clonality and antibiotic susceptibility of pathogenic Yersinia enterocolitica from swine feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Swine are the only known animal reservoir of Yersinia enterocolitica (YE), a human pathogen. Since YE is a fecal organism of swine, the primary goal of this study was to evaluate the prevalence, serotype, virulence plasmid (pYV)-associated characteristics, clonality, and antibiotic su...

  3. Clonal genetic structure and diversity in populations of an aquatic plant with combined vs. separate sexes.

    PubMed

    Yakimowski, Sarah B; Barrett, Spencer C H

    2014-06-01

    Clonality is often implicated in models of the evolution of dioecy, but few studies have explicitly compared clonal structure between plant sexual systems, or between the sexes in dioecious populations. Here, we exploit the occurrence of monoecy and dioecy in clonal Sagittaria latifola (Alismataceae) to evaluate two main hypotheses: (i) clone sizes are smaller in monoecious than dioecious populations, because of constraints imposed on clone size by costs associated with geitonogamy; (ii) in dioecious populations, male clones are larger and flower more often than female clones because of sex-differential reproductive costs. Differences in clone size and flowering could result in discordance between ramet- and genet-based sex ratios. We used spatially explicit sampling to address these hypotheses in 10 monoecious and 11 dioecious populations of S. latifolia at the northern range limit in Eastern North America. In contrast to our predictions, monoecious clones were significantly larger than dioecious clones, probably due to their higher rates of vegetative growth and corm production, and in dioecious populations, there was no difference in clone size between females and males; ramet- and genet-based sex ratios were therefore highly correlated. Genotypic diversity declined with latitude for both sexual systems, but monoecious populations exhibited lower genotypic richness. Differences in life history between the sexual systems of S. latifolia appear to be the most important determinants of clonal structure and diversity.

  4. Poppr: an R package for genetic analysis of populations with mixed (clonal/sexual) reproduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poppr is an R package for analysis of population genetic data. It extends the adegenet package and provides several novel tools, particularly with regard to analysis of data from admixed, clonal, and/or sexual populations. Currently, poppr can be used for dominant/codominant and haploid/diploid gene...

  5. Background and initial evaluations of recently introduced cultivars distributed by the Citrus Clonal Protection Program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Each year the Citrus Clonal Protection Program (CCPP) distributes budwood of new, potentially important commercial citrus cultivars as they are re- leased from quarantine after completing a thorough “Variety Introduction (VI)” disease testing and therapy program. This article is the second in a seri...

  6. Descriptions of new varieties recently distributed from the Citrus Clonal Protection Program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Citrus Clonal Protection Program (CCPP) is operated through the Department of Plant Pathology and Microbiology at University of California (UC) Riverside and is funded in large part by The California Citrus Research Board (CRB). The CCPP processes citrus propagative material in two phases. First...

  7. Serogroup and Clonal Characterization of Czech Invasive Neisseria meningitidis Strains Isolated from 1971 to 2015

    PubMed Central

    Jandova, Zuzana; Musilek, Martin; Vackova, Zuzana; Kozakova, Jana; Krizova, Pavla

    2016-01-01

    Background This study presents antigenic and genetic characteristics of Neisseria meningitidis strains recovered from invasive meningococcal disease (IMD) in the Czech Republic in 1971–2015. Material and Methods A total of 1970 isolates from IMD, referred to the National Reference Laboratory for Meningococcal Infections in 1971–2015, were studied. All isolates were identified and characterized by conventional biochemical and serological tests. Most isolates (82.5%) were characterized by multilocus sequence typing method. Results In the study period 1971–2015, the leading serogroup was B (52.4%), most often assigned to clonal complexes cc32, cc41/44, cc18, and cc269. A significant percentage of strains were of serogroup C (41.4%), with high clonal homogeneity due to hyperinvasive complex cc11, which played an important role in IMD in the Czech Republic in the mid-1990s. Serogroup Y isolates, mostly assigned to cc23, and isolates of clonally homogeneous serogroup W have also been recovered more often over the last years. Conclusion The incidence of IMD and distribution of serogroups and clonal complexes of N. meningitidis in the Czech Republic varied over time, as can be seen from the long-term monitoring, including molecular surveillance data. Data from the conventional and molecular IMD surveillance are helpful in refining the antimeningococcal vaccination strategy in the Czech Republic. PMID:27936105

  8. Ephemeral clonal integration in Calathea marantifolia (Marantaceae): Evidence of diminished integration over time.

    PubMed

    Matlaga, David P; da S L Sternberg, Leonel

    2009-02-01

    A major advantage of clonal growth forms is the intergenerational transfer of resources through vascular connections (clonal integration). Connections linking ramets can be persistent or ephemeral. For species with ephemeral connections, whether the extent of clonal integration changes over time is unclear. To address this issue, we tracked water movement using an isotopic label and assessed the demographic performance of parent and offspring ramets over time in a severing experiment. Our study system was the understory herb Calathea marantifolia, which has parent ramets that produce vegetative bulbils (clonal offspring) that pass through distinct pre- and post-rooting stages. Little water was transported between parents and offspring, and the direction of movement was primarily from parent to pre-rooting offspring. Anatomical observations of inter-ramet connections showed that vascular bundles were twice as abundant in parent stems compared to inter-ramet connections. Severing inter-ramet connections reduced the growth of offspring ramets but not parents. Survival of pre-rooting offspring was reduced by 10% due to severing, but post-rooting offspring were not affected. Our results suggest that offspring ramets of C. marantifolia are weaned from their parent as they progress from pre- to post-rooting stages.

  9. Floral variation and environmental heterogeneity in a tristylous clonal aquatic of the Pantanal wetlands of Brazil

    PubMed Central

    Leme da Cunha, Nicolay; Fischer, Erich; Lorenz-Lemke, Aline P.; Barrett, Spencer C. H.

    2014-01-01

    Background and Aims The balance between stochastic forces and frequency-dependent mating largely governs style morph frequencies in heterostylous populations. In clonal species, deviations from equal morph ratios often result from founder events and unfavourable conditions for sexual reproduction. The aim of this study was to investigate whether different flooding regimes, because of their influence on sexual vs. clonal reproduction, are associated with regional variation in morph frequencies and floral trait differentiation in populations of the clonal, tristylous, aquatic Eichhornia azurea (Pontederiaceae) in the Pantanal wetlands of Brazil. Methods Style morph frequencies were sampled from 73 populations distributed across four flooding regimes differing in depth and duration. Measurements of flower size, sex-organ dimension, pollen size and pollen production were made in selected populations, and pollinator assemblages and their functional traits were recorded. Key Results Most populations of E. azurea were tristylous (78 %), but the majority exhibited uneven morph ratios. The frequency of the mid-styled morph was significantly lower than that of the long- and short-styled morphs. Morph evenness was positively associated with population size but not with flooding regime. There were significant phenotypic differences among flooding regimes for all floral traits, including populations with reduced flower size, sex-organ length and smaller pollen. Pollinator assemblages varied with flood duration. Conclusions The similar morph structure and evenness of populations, regardless of flooding regime, suggest that sexual reproduction and clonal dispersal are sufficiently common to prevent the signature of founder events from dominating in a region. However, the pervasive occurrence of biased morph ratios in most populations suggests that many are in a non-equilibrium state. The reduced frequency of the mid-styled morph in trimorphic and dimorphic populations may be

  10. Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection.

    PubMed

    Tchesnokova, Veronika; Avagyan, Hovhannes; Rechkina, Elena; Chan, Diana; Muradova, Mariya; Haile, Helen Ghirmai; Radey, Matthew; Weissman, Scott; Riddell, Kim; Scholes, Delia; Johnson, James R; Sokurenko, Evgeni V

    2017-01-01

    Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients' urine within 25-35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care.

  11. Bacterial clonal diagnostics as a tool for evidence-based empiric antibiotic selection

    PubMed Central

    Tchesnokova, Veronika; Avagyan, Hovhannes; Rechkina, Elena; Chan, Diana; Muradova, Mariya; Haile, Helen Ghirmai; Radey, Matthew; Weissman, Scott; Riddell, Kim; Scholes, Delia; Johnson, James R.

    2017-01-01

    Despite the known clonal distribution of antibiotic resistance in many bacteria, empiric (pre-culture) antibiotic selection still relies heavily on species-level cumulative antibiograms, resulting in overuse of broad-spectrum agents and excessive antibiotic/pathogen mismatch. Urinary tract infections (UTIs), which account for a large share of antibiotic use, are caused predominantly by Escherichia coli, a highly clonal pathogen. In an observational clinical cohort study of urgent care patients with suspected UTI, we assessed the potential for E. coli clonal-level antibiograms to improve empiric antibiotic selection. A novel PCR-based clonotyping assay was applied to fresh urine samples to rapidly detect E. coli and the urine strain's clonotype. Based on a database of clonotype-specific antibiograms, the acceptability of various antibiotics for empiric therapy was inferred using a 20%, 10%, and 30% allowed resistance threshold. The test's performance characteristics and possible effects on prescribing were assessed. The rapid test identified E. coli clonotypes directly in patients’ urine within 25–35 minutes, with high specificity and sensitivity compared to culture. Antibiotic selection based on a clonotype-specific antibiogram could reduce the relative likelihood of antibiotic/pathogen mismatch by ≥ 60%. Compared to observed prescribing patterns, clonal diagnostics-guided antibiotic selection could safely double the use of trimethoprim/sulfamethoxazole and minimize fluoroquinolone use. In summary, a rapid clonotyping test showed promise for improving empiric antibiotic prescribing for E. coli UTI, including reversing preferential use of fluoroquinolones over trimethoprim/sulfamethoxazole. The clonal diagnostics approach merges epidemiologic surveillance, antimicrobial stewardship, and molecular diagnostics to bring evidence-based medicine directly to the point of care. PMID:28350870

  12. [Effects of light intensity contrast on clonal integration of Spartina anglica].

    PubMed

    Jiang, Xing-Xing; Dong, Bi-Cheng; Luo, Fang-Li; Zhu, Rui; Xu, Xi-Yi; Li, Hong-Li; Yu, Fei-Hai

    2014-10-01

    We conducted a greenhouse experiment to test how clonal integration affected the growth responses of Spartina anglica to light intensity heterogeneity in light availability and whether such effects depended on contrast light intensity. The experiment had three homogeneous treatments and two heterogeneous treatments. In the homogeneous treatments, both ramets of a connected ramet pair were unshaded (high light intensity), moderately shaded (medium light intensity, 70% of the high light intensity) and deeply shaded (low light intensity, 30% of the high light intensity). In the heterogeneous treatments, one ramet of a pair was unshaded, but its connected ramet was either moderately shaded (low light intensity contrast) or deeply shaded (high light intensity contrast). In the homogeneous treatments, biomass of S. anglica was significantly higher in the high light intensity treatment than in the medium and low light intensity treatments. Number of leaves, root length, and total biomass were significantly higher in the shaded ramet in the heterogeneous treatment with low light intensity contrast than in the ramet in the homogeneous treatment with medium light intensity. Final size and mass were not significantly different between the unshaded ramet in the heterogeneous treatment with low light intensity contrast and the ramets in the homogeneous high light intensity treatment. These results suggested that clonal integration benefitted a shaded ramet with little cost to an unshaded ramet when contrast in light intensity was low. However, effects of clonal integration were not significant when contrast was high. It therefore appeared that effects of clonal integration on the growth of S. anglica did not increase with increasing light intensity contrast. In natural habitats, clonal integration might improve growth of S. anglica when its ramets are moderately shaded by other plants but not when they are deeply shaded.

  13. Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

    PubMed Central

    Campbell, F; Williams, G T; Appleton, M A; Dixon, M F; Harris, M; Williams, E D

    1996-01-01

    BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems. PMID:8944567

  14. Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension.

    PubMed

    Kwon, Young-In I; Vattem, Dhiraj A; Shetty, Kalidas

    2006-01-01

    In the current study, we screened 7 clonal lines from single seed phenotypes of Lamiaceae family for the inhibition of alpha-amylase, alpha-glucosidase and angiotensin converting enzyme (ACE) inhibitory activity. Water extracts of oregano had the highest alpha-glucosidase inhibition activity (93.7%), followed by chocolate mint (85.9%) and lemon balm (83.9%). Sage (78.4 %), and three different clonal lines of rosemary: rosemary LA (71.4%), rosemary 6 (68.4%) and rosemary K-2 (67.8%) also showed significant alpha-glucosidase inhibitory activity. The alpha-glucosidase inhibitory activity of the extracts was compared to selected specific phenolics detected in the extracts using HPLC. Catechin had the highest alpha-glucosidase inhibitiory activity (99.6 %) followed by caffeic acid (91.3 %), rosmarinic acid (85.1%) and resveratrol (71.1 %). Catechol (64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity. Results suggested that alpha-glucosidase inhibitory activity of the clonal extracts correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. The clonal extracts of the herbs and standard phenolics tested in this study did not have any effect on the alpha-amylase activity. We also investigated the ability of the clonal extracts to inhibit rabbit lung angiotensin I-converting enzyme (ACE). The water extracts of rosemary, rosemary LA had the highest ACE inhibitory activity (90.5%), followed by lemon balm (81.9%) and oregano (37.4 %). Lower levels of ACE inhibition were observed with ethanol extracts of oregano (18.5 %) and lemon balm (0.5 %). Among the standard phenolics only resveratrol (24.1 %), hydroxybenzoic acid (19.3 %) and coumaric acid (2.3 %) had ACE inhibitory activity.

  15. Clonal multipotency of skeletal muscle-derived stem cells between mesodermal and ectodermal lineage.

    PubMed

    Tamaki, Tetsuro; Okada, Yoshinori; Uchiyama, Yoshiyasu; Tono, Kayoko; Masuda, Maki; Wada, Mika; Hoshi, Akio; Ishikawa, Tetsuya; Akatsuka, Akira

    2007-09-01

    The differentiation potential of skeletal muscle-derived stem cells (MDSCs) after in vitro culture and in vivo transplantation has been extensively studied. However, the clonal multipotency of MDSCs has yet to be fully determined. Here, we show that single skeletal muscle-derived CD34-/CD45- (skeletal muscle-derived double negative [Sk-DN]) cells exhibit clonal multipotency that can give rise to myogenic, vasculogenic, and neural cell lineages after in vivo single cell-derived single sphere implantation and in vitro clonal single cell culture. Muscles from green fluorescent protein (GFP) transgenic mice were enzymatically dissociated and sorted based on CD34 and CD45. Sk-DN cells were clone-sorted into a 96-well plate and were cultured in collagen-based medium with basic fibroblast growth factor and epidermal growth factor for 14 days. Individual colony-forming units (CFUs) were then transplanted directly into severely damaged muscle together with 1 x 10(5) competitive carrier Sk-DN cells obtained from wild-type mice muscle expanded for 5 days under the same culture conditions using 35-mm culture dishes. Four weeks after transplantation, implanted GFP+ cells demonstrated differentiation into endothelial, vascular smooth muscle, skeletal muscle, and neural cell (Schwann cell) lineages. This multipotency was also confirmed by expression of mRNA markers for myogenic (MyoD, myf5), neural (Musashi-1, Nestin, neural cell adhesion molecule-1, peripheral myelin protein-22, Nucleostemin), and vascular (alpha-smooth muscle actin, smoothelin, vascular endothelial-cadherin, tyrosine kinase-endothelial) stem cells by clonal (single-cell derived) single-sphere reverse transcription-polymerase chain reaction. Approximately 70% of clonal CFUs exhibited expression of all three cell lineages. These findings support the notion that Sk-DN cells are a useful tool for damaged muscle-related tissue reconstitution by synchronized vasculogenesis, myogenesis, and neurogenesis.

  16. Perception of neighboring plants by rhizomes and roots: morphological manifestations of a clonal plant

    USGS Publications Warehouse

    Huber-Sannwald, Elisabeth; Pyke, David A.; Caldwell, M.M.

    1997-01-01

    A previous study showed that clonal morphology of the rhizomatous grass Elymus lanceolatus ssp. lanceolatus (Scibner & J.G. Smith Gould) was influenced more by neighbouring root systems than by the local distribution of nutrients. In this study we determine whether individual rhizomes or roots of E. lanceolatus perceive neighbouring root systems and how this is manifested in morphological responses of E. lanceolatus clones. Elymus lanceolatus was grown in the same bin with Pseudoroegneria spicata (Pursh) A. Love or Agropyron desertorum (Fisch. ex Link) Schult. plants. Elymus lanceolatus was separated from its neighbours by different barriers. The barriers allowed either only E. lanceolatus roots; only a single E. lanceolatus primary rhizome; or both roots and rhizomes to contact the neighbour root system. When only a single E. lanceolatus primary rhizome with potentially developing branching rhizomes made contact with the neighbour, the clonal structure of E. lanceolatus was modified more with P. spicata as the neighbour than with A. desertorum. With root contact of E. lanceolatus alone there was a similar effect with the neighbouring plants, but there was a more marked inhibitory effect on E. lanceolatus clonal growth with P. spicata than with A. desertorum, compared with the treatment with only a single rhizome in contact with the neighbour. Root resource competition in the unconstrained treatment (roots and rhizomes) between neighbouring plant and E. lanceolatus was more apparent with A. desertorum than with P. spicata. This study is one of the first to document that rhizome and root contact of a clonal plant with its neighbours may induce different clonal responses depending on the species of neighbour.

  17. Effects of nutrient patches and root systems on the clonal plasticity of a rhizomatous grass

    USGS Publications Warehouse

    Huber-Sannwald, Elisabeth; Pyke, David A.; Caldwell, M.M.; Durham, S.

    1998-01-01

    Clonal plant foraging has been examined primarily on individual clones exposed to resource-poor and resource-rich environments. We designed an experiment to examine the clonal foraging behavior of the rhizomatous grass Elymus lanceolatus ssp. lanceolatus under the influence of neighboring plant root systems in a heterogeneous nutrient environment. Individual Elymus clones were planted in large bins together with one of three neighboring grass species, Agropyron desertorum, Pseudoroegneria spicata, or Bromus tectorum, which differ in rooting density and growth activity. The position of Elymus clones was manipulated so rhizomes encountered a short-duration nutrient patch and subsequently root systems of the neighboring plants. Unexpectedly, the morphological plasticity of the perennial grass Elymus lanceolatus ssp. lanceolatus was influenced by the presence of the neighboring species much more than by the local nutrient enrichments, although nutrient patches did amplify some of the foraging responses. Elymus rhizomes branched readily and initiated large daughter plants as they encountered the low-density root systems of Pseudoroegneria. When Elymus encountered the fine, dense root systems of the annual Bromus, clonal expansion was initially reduced. Yet, after the short growing season of Bromus, Elymus resumed clonal expansion and produced several daughter plants. Elymus clones were most constrained by the fine, dense root systems of Agropyron desertorum. In this case, a few, long rhizomes avoided the densely rooted soil environment by growing aboveground as stolons crossing over the Agropyron tussocks. Elymus clonal biomass was largest in neighborhoods of Pseudoroegneria, intermediate in neighborhoods with Bromus, and smallest in neighborhoods with Agropyron. The latter were approximately half the size of those in the Pseudoroegneria environments. Elymus growth could not be explained by simple resource competition alone; other mechanisms must have been involved in

  18. Parallel processor engine model program

    NASA Technical Reports Server (NTRS)

    Mclaughlin, P.

    1984-01-01

    The Parallel Processor Engine Model Program is a generalized engineering tool intended to aid in the design of parallel processing real-time simulations of turbofan engines. It is written in the FORTRAN programming language and executes as a subset of the SOAPP simulation system. Input/output and execution control are provided by SOAPP; however, the analysis, emulation and simulation functions are completely self-contained. A framework in which a wide variety of parallel processing architectures could be evaluated and tools with which the parallel implementation of a real-time simulation technique could be assessed are provided.

  19. Parallel processing and expert systems

    NASA Technical Reports Server (NTRS)

    Yan, Jerry C.; Lau, Sonie

    1991-01-01

    Whether it be monitoring the thermal subsystem of Space Station Freedom, or controlling the navigation of the autonomous rover on Mars, NASA missions in the 90's cannot enjoy an increased level of autonomy without the efficient use of expert systems. Merely increasing the computational speed of uniprocessors may not be able to guarantee that real time demands are met for large expert systems. Speed-up via parallel processing must be pursued alongside the optimization of sequential implementations. Prototypes of parallel expert systems have been built at universities and industrial labs in the U.S. and Japan. The state-of-the-art research in progress related to parallel execution of expert systems was surveyed. The survey is divided into three major sections: (1) multiprocessors for parallel expert systems; (2) parallel languages for symbolic computations; and (3) measurements of parallelism of expert system. Results to date indicate that the parallelism achieved for these systems is small. In order to obtain greater speed-ups, data parallelism and application parallelism must be exploited.

  20. Parallel Programming in the Age of Ubiquitous Parallelism

    NASA Astrophysics Data System (ADS)

    Pingali, Keshav

    2014-04-01

    Multicore and manycore processors are now ubiquitous, but parallel programming remains as difficult as it was 30-40 years ago. During this time, our community has explored many promising approaches including functional and dataflow languages, logic programming, and automatic parallelization using program analysis and restructuring, but none of these approaches has succeeded except in a few niche application areas. In this talk, I will argue that these problems arise largely from the computation-centric foundations and abstractions that we currently use to think about parallelism. In their place, I will propose a novel data-centric foundation for parallel programming called the operator formulation in which algorithms are described in terms of actions on data. The operator formulation shows that a generalized form of data-parallelism called amorphous data-parallelism is ubiquitous even in complex, irregular graph applications such as mesh generation/refinement/partitioning and SAT solvers. Regular algorithms emerge as a special case of irregular ones, and many application-specific optimization techniques can be generalized to a broader context. The operator formulation also leads to a structural analysis of algorithms called TAO-analysis that provides implementation guidelines for exploiting parallelism efficiently. Finally, I will describe a system called Galois based on these ideas for exploiting amorphous data-parallelism on multicores and GPUs

  1. Trajectories in parallel optics.

    PubMed

    Klapp, Iftach; Sochen, Nir; Mendlovic, David

    2011-10-01

    In our previous work we showed the ability to improve the optical system's matrix condition by optical design, thereby improving its robustness to noise. It was shown that by using singular value decomposition, a target point-spread function (PSF) matrix can be defined for an auxiliary optical system, which works parallel to the original system to achieve such an improvement. In this paper, after briefly introducing the all optics implementation of the auxiliary system, we show a method to decompose the target PSF matrix. This is done through a series of shifted responses of auxiliary optics (named trajectories), where a complicated hardware filter is replaced by postprocessing. This process manipulates the pixel confined PSF response of simple auxiliary optics, which in turn creates an auxiliary system with the required PSF matrix. This method is simulated on two space variant systems and reduces their system condition number from 18,598 to 197 and from 87,640 to 5.75, respectively. We perform a study of the latter result and show significant improvement in image restoration performance, in comparison to a system without auxiliary optics and to other previously suggested hybrid solutions. Image restoration results show that in a range of low signal-to-noise ratio values, the trajectories method gives a significant advantage over alternative approaches. A third space invariant study case is explored only briefly, and we present a significant improvement in the matrix condition number from 1.9160e+013 to 34,526.

  2. High Performance Parallel Architectures

    NASA Technical Reports Server (NTRS)

    El-Ghazawi, Tarek; Kaewpijit, Sinthop

    1998-01-01

    Traditional remote sensing instruments are multispectral, where observations are collected at a few different spectral bands. Recently, many hyperspectral instruments, that can collect observations at hundreds of bands, have been operational. Furthermore, there have been ongoing research efforts on ultraspectral instruments that can produce observations at thousands of spectral bands. While these remote sensing technology developments hold great promise for new findings in the area of Earth and space science, they present many challenges. These include the need for faster processing of such increased data volumes, and methods for data reduction. Dimension Reduction is a spectral transformation, aimed at concentrating the vital information and discarding redundant data. One such transformation, which is widely used in remote sensing, is the Principal Components Analysis (PCA). This report summarizes our progress on the development of a parallel PCA and its implementation on two Beowulf cluster configuration; one with fast Ethernet switch and the other with a Myrinet interconnection. Details of the implementation and performance results, for typical sets of multispectral and hyperspectral NASA remote sensing data, are presented and analyzed based on the algorithm requirements and the underlying machine configuration. It will be shown that the PCA application is quite challenging and hard to scale on Ethernet-based clusters. However, the measurements also show that a high- performance interconnection network, such as Myrinet, better matches the high communication demand of PCA and can lead to a more efficient PCA execution.

  3. Heterogeneous water supply affects growth and benefits of clonal integration between co-existing invasive and native Hydrocotyle species

    PubMed Central

    Wang, Yong-Jian; Bai, Yun-Fei; Zeng, Shi-Qi; Yao, Bin; Wang, Wen; Luo, Fang-Li

    2016-01-01

    Spatial patchiness and temporal variability in water availability are common in nature under global climate change, which can remarkably influence adaptive responses of clonal plants, i.e. clonal integration (translocating resources between connected ramets). However, little is known about the effects of spatial patchiness and temporal heterogeneity in water on growth and clonal integration between congeneric invasive and native Hydrocotyle species. In a greenhouse experiment, we subjected severed or no severed (intact) fragments of Hydrocotyle vulgaris, a highly invasive species in China, and its co-existing, native congener H. sibthorpioides to different spatial patchiness (homogeneous and patchy) and temporal interval (low and high interval) in water supply. Clonal integration had significant positive effects on growth of both species. In the homogeneous water conditions, clonal integration greatly improved the growth in fragments of both species under low interval in water. However, in the patchy water conditions, clonal integration significantly increased growth in both ramets and fragments of H. vulgaris under high interval in water. Therefore, spatial patchiness and temporal interval in water altered the effects of clonal integration of both species, especially for H. vulgaris. The adaptation of H. vulgaris might lead to invasive growth and potential spread under the global water variability. PMID:27439691

  4. Computer Simulation (Microcultures): An Effective Model for Multicultural Education.

    ERIC Educational Resources Information Center

    Nelson, Jorge O.

    This paper presents a rationale for using high-fidelity computer simulation in planning for and implementing effective multicultural education strategies. Using computer simulation, educators can begin to understand and plan for the concept of cultural sensitivity in delivering instruction. The model promises to emphasize teachers' understanding…

  5. How Clonal Is Clonal? Genome Plasticity across Multicellular Segments of a "Candidatus Marithrix sp." Filament from Sulfidic, Briny Seafloor Sediments in the Gulf of Mexico.

    PubMed

    Salman-Carvalho, Verena; Fadeev, Eduard; Joye, Samantha B; Teske, Andreas

    2016-01-01

    "Candidatus Marithrix" is a recently described lineage within the group of large sulfur bacteria (Beggiatoaceae, Gammaproteobacteria). This genus of bacteria comprises vacuolated, attached-living filaments that inhabit the sediment surface around vent and seep sites in the marine environment. A single filament is ca. 100 μm in diameter, several millimeters long, and consists of hundreds of clonal cells, which are considered highly polyploid. Based on these characteristics, "Candidatus Marithrix" was used as a model organism for the assessment of genomic plasticity along segments of a single filament using next generation sequencing to possibly identify hotspots of microevolution. Using six consecutive segments of a single filament sampled from a mud volcano in the Gulf of Mexico, we recovered ca. 90% of the "Candidatus Marithrix" genome in each segment. There was a high level of genome conservation along the filament with average nucleotide identities between 99.98 and 100%. Different approaches to assemble all reads into a complete consensus genome could not fill the gaps. Each of the six segment datasets encoded merely a few hundred unique nucleotides and 5 or less unique genes-the residual content was redundant in all datasets. Besides the overall high genomic identity, we identified a similar number of single nucleotide polymorphisms (SNPs) between the clonal segments, which are comparable to numbers reported for other clonal organisms. An increase of SNPs with greater distance of filament segments was not observed. The polyploidy of the cells was apparent when analyzing the heterogeneity of reads within a segment. Here, a strong increase in single nucleotide variants, or "intrasegmental sequence heterogeneity" (ISH) events, was observed. These sites may represent hotspots for genome plasticity, and possibly microevolution, since two thirds of these variants were not co-localized across the genome copies of the multicellular filament.

  6. Core Genome Multilocus Sequence Typing for Identification of Globally Distributed Clonal Groups and Differentiation of Outbreak Strains of Listeria monocytogenes

    PubMed Central

    Gonzalez-Escalona, Narjol; Hammack, Thomas S.; Allard, Marc W.; Strain, Errol A.; Brown, Eric W.

    2016-01-01

    ABSTRACT Many listeriosis outbreaks are caused by a few globally distributed clonal groups, designated clonal complexes or epidemic clones, of Listeria monocytogenes, several of which have been defined by classic multilocus sequence typing (MLST) schemes targeting 6 to 8 housekeeping or virulence genes. We have developed and evaluated core genome MLST (cgMLST) schemes and applied them to isolates from multiple clonal groups, including those associated with 39 listeriosis outbreaks. The cgMLST clusters were congruent with MLST-defined clonal groups, which had various degrees of diversity at the whole-genome level. Notably, cgMLST could distinguish among outbreak strains and epidemiologically unrelated strains of the same clonal group, which could not be achieved using classic MLST schemes. The precise selection of cgMLST gene targets may not be critical for the general identification of clonal groups and outbreak strains. cgMLST analyses further identified outbreak strains, including those associated with recent outbreaks linked to contaminated French-style cheese, Hispanic-style cheese, stone fruit, caramel apple, ice cream, and packaged leafy green salad, as belonging to major clonal groups. We further developed lineage-specific cgMLST schemes, which can include accessory genes when core genomes do not possess sufficient diversity, and this provided additional resolution over species-specific cgMLST. Analyses of isolates from different common-source listeriosis outbreaks revealed various degrees of diversity, indicating that the numbers of allelic differences should always be combined with cgMLST clustering and epidemiological evidence to define a listeriosis outbreak. IMPORTANCE Classic multilocus sequence typing (MLST) schemes targeting internal fragments of 6 to 8 genes that define clonal complexes or epidemic clones have been widely employed to study L. monocytogenes biodiversity and its relation to pathogenicity potential and epidemiology. We demonstrated

  7. Parallel Computational Protein Design

    PubMed Central

    Zhou, Yichao; Donald, Bruce R.; Zeng, Jianyang

    2016-01-01

    Computational structure-based protein design (CSPD) is an important problem in computational biology, which aims to design or improve a prescribed protein function based on a protein structure template. It provides a practical tool for real-world protein engineering applications. A popular CSPD method that guarantees to find the global minimum energy solution (GMEC) is to combine both dead-end elimination (DEE) and A* tree search algorithms. However, in this framework, the A* search algorithm can run in exponential time in the worst case, which may become the computation bottleneck of large-scale computational protein design process. To address this issue, we extend and add a new module to the OSPREY program that was previously developed in the Donald lab [1] to implement a GPU-based massively parallel A* algorithm for improving protein design pipeline. By exploiting the modern GPU computational framework and optimizing the computation of the heuristic function for A* search, our new program, called gOSPREY, can provide up to four orders of magnitude speedups in large protein design cases with a small memory overhead comparing to the traditional A* search algorithm implementation, while still guaranteeing the optimality. In addition, gOSPREY can be configured to run in a bounded-memory mode to tackle the problems in which the conformation space is too large and the global optimal solution cannot be computed previously. Furthermore, the GPU-based A* algorithm implemented in the gOSPREY program can be combined with the state-of-the-art rotamer pruning algorithms such as iMinDEE [2] and DEEPer [3] to also consider continuous backbone and side-chain flexibility. PMID:27914056

  8. Parallel Adaptive Mesh Refinement

    SciTech Connect

    Diachin, L; Hornung, R; Plassmann, P; WIssink, A

    2005-03-04

    As large-scale, parallel computers have become more widely available and numerical models and algorithms have advanced, the range of physical phenomena that can be simulated has expanded dramatically. Many important science and engineering problems exhibit solutions with localized behavior where highly-detailed salient features or large gradients appear in certain regions which are separated by much larger regions where the solution is smooth. Examples include chemically-reacting flows with radiative heat transfer, high Reynolds number flows interacting with solid objects, and combustion problems where the flame front is essentially a two-dimensional sheet occupying a small part of a three-dimensional domain. Modeling such problems numerically requires approximating the governing partial differential equations on a discrete domain, or grid. Grid spacing is an important factor in determining the accuracy and cost of a computation. A fine grid may be needed to resolve key local features while a much coarser grid may suffice elsewhere. Employing a fine grid everywhere may be inefficient at best and, at worst, may make an adequately resolved simulation impractical. Moreover, the location and resolution of fine grid required for an accurate solution is a dynamic property of a problem's transient features and may not be known a priori. Adaptive mesh refinement (AMR) is a technique that can be used with both structured and unstructured meshes to adjust local grid spacing dynamically to capture solution features with an appropriate degree of resolution. Thus, computational resources can be focused where and when they are needed most to efficiently achieve an accurate solution without incurring the cost of a globally-fine grid. Figure 1.1 shows two example computations using AMR; on the left is a structured mesh calculation of a impulsively-sheared contact surface and on the right is the fuselage and volume discretization of an RAH-66 Comanche helicopter [35]. Note the

  9. A Parallel Particle Swarm Optimizer

    DTIC Science & Technology

    2003-01-01

    by a computationally demanding biomechanical system identification problem, we introduce a parallel implementation of a stochastic population based...concurrent computation. The parallelization of the Particle Swarm Optimization (PSO) algorithm is detailed and its performance and characteristics demonstrated for the biomechanical system identification problem as example.

  10. Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy: comparison with clinical and biologic factors.

    PubMed

    Goldstein, Neal S; Vicini, Frank A; Hunter, Susan; Odish, Eva; Forbes, Suzy; Kraus, Daniel; Kestin, Larry L

    2005-05-01

    We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

  11. Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study

    PubMed Central

    Mottok, Anja; Boyle, Merrill; Tan, King; Meissner, Barbara; Bashashati, Ali; Roth, Andrew; Shumansky, Karey; Nielsen, Cydney; Giné, Eva; Moore, Richard; Morin, Ryan D.; Sehn, Laurie H.; Tousseyn, Thomas; Dogan, Ahmet; Scott, David W.; Steidl, Christian; Gascoyne, Randy D.; Shah, Sohrab P.

    2016-01-01

    Background Follicular lymphoma (FL) is an indolent, yet incurable B cell malignancy. A subset of patients experience an increased mortality rate driven by two distinct clinical end points: histological transformation and early progression after immunochemotherapy. The nature of tumor clonal dynamics leading to these clinical end points is poorly understood, and previously determined genetic alterations do not explain the majority of transformed cases or accurately predict early progressive disease. We contend that detailed knowledge of the expansion patterns of specific cell populations plus their associated mutations would provide insight into therapeutic strategies and disease biology over the time course of FL clinical histories. Methods and Findings Using a combination of whole genome sequencing, targeted deep sequencing, and digital droplet PCR on matched diagnostic and relapse specimens, we deciphered the constituent clonal populations in 15 transformation cases and 6 progression cases, and measured the change in clonal population abundance over time. We observed widely divergent patterns of clonal dynamics in transformed cases relative to progressed cases. Transformation specimens were generally composed of clones that were rare or absent in diagnostic specimens, consistent with dramatic clonal expansions that came to dominate the transformation specimens. This pattern was independent of time to transformation and treatment modality. By contrast, early progression specimens were composed of clones that were already present in the diagnostic specimens and exhibited only moderate clonal dynamics, even in the presence of immunochemotherapy. Analysis of somatic mutations impacting 94 genes was undertaken in an extension cohort consisting of 395 samples from 277 patients in order to decipher disrupted biology in the two clinical end points. We found 12 genes that were more commonly mutated in transformed samples than in the preceding FL tumors, including TP53, B2

  12. Effects of Spatial Patch Arrangement and Scale of Covarying Resources on Growth and Intraspecific Competition of a Clonal Plant

    PubMed Central

    Wang, Yong-Jian; Shi, Xue-Ping; Meng, Xue-Feng; Wu, Xiao-Jing; Luo, Fang-Li; Yu, Fei-Hai

    2016-01-01

    Spatial heterogeneity in two co-variable resources such as light and water availability is common and can affect the growth of clonal plants. Several studies have tested effects of spatial heterogeneity in the supply of a single resource on competitive interactions of plants, but none has examined those of heterogeneous distribution of two co-variable resources. In a greenhouse experiment, we grew one (without intraspecific competition) or nine isolated ramets (with competition) of a rhizomatous herb Iris japonica under a homogeneous environment and four heterogeneous environments differing in patch arrangement (reciprocal and parallel patchiness of light and soil water) and patch scale (large and small patches of light and water). Intraspecific competition significantly decreased the growth of I. japonica, but at the whole container level there were no significant interaction effects of competition by spatial heterogeneity or significant effect of heterogeneity on competitive intensity. Irrespective of competition, the growth of I. japonica in the high and the low water patches did not differ significantly in the homogeneous treatments, but it was significantly larger in the high than in the low water patches in the heterogeneous treatments with large patches. For the heterogeneous treatments with small patches, the growth of I. japonica was significantly larger in the high than in the low water patches in the presence of competition, but such an effect was not significant in the absence of competition. Furthermore, patch arrangement and patch scale significantly affected competitive intensity at the patch level. Therefore, spatial heterogeneity in light and water supply can alter intraspecific competition at the patch level and such effects depend on patch arrangement and patch scale. PMID:27375630

  13. Effects of Spatial Patch Arrangement and Scale of Covarying Resources on Growth and Intraspecific Competition of a Clonal Plant.

    PubMed

    Wang, Yong-Jian; Shi, Xue-Ping; Meng, Xue-Feng; Wu, Xiao-Jing; Luo, Fang-Li; Yu, Fei-Hai

    2016-01-01

    Spatial heterogeneity in two co-variable resources such as light and water availability is common and can affect the growth of clonal plants. Several studies have tested effects of spatial heterogeneity in the supply of a single resource on competitive interactions of plants, but none has examined those of heterogeneous distribution of two co-variable resources. In a greenhouse experiment, we grew one (without intraspecific competition) or nine isolated ramets (with competition) of a rhizomatous herb Iris japonica under a homogeneous environment and four heterogeneous environments differing in patch arrangement (reciprocal and parallel patchiness of light and soil water) and patch scale (large and small patches of light and water). Intraspecific competition significantly decreased the growth of I. japonica, but at the whole container level there were no significant interaction effects of competition by spatial heterogeneity or significant effect of heterogeneity on competitive intensity. Irrespective of competition, the growth of I. japonica in the high and the low water patches did not differ significantly in the homogeneous treatments, but it was significantly larger in the high than in the low water patches in the heterogeneous treatments with large patches. For the heterogeneous treatments with small patches, the growth of I. japonica was significantly larger in the high than in the low water patches in the presence of competition, but such an effect was not significant in the absence of competition. Furthermore, patch arrangement and patch scale significantly affected competitive intensity at the patch level. Therefore, spatial heterogeneity in light and water supply can alter intraspecific competition at the patch level and such effects depend on patch arrangement and patch scale.

  14. The Galley Parallel File System

    NASA Technical Reports Server (NTRS)

    Nieuwejaar, Nils; Kotz, David

    1996-01-01

    Most current multiprocessor file systems are designed to use multiple disks in parallel, using the high aggregate bandwidth to meet the growing I/0 requirements of parallel scientific applications. Many multiprocessor file systems provide applications with a conventional Unix-like interface, allowing the application to access multiple disks transparently. This interface conceals the parallelism within the file system, increasing the ease of programmability, but making it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. In addition to providing an insufficient interface, most current multiprocessor file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic scientific multiprocessor workloads. We discuss Galley's file structure and application interface, as well as the performance advantages offered by that interface.

  15. Parallel contingency statistics with Titan.

    SciTech Connect

    Thompson, David C.; Pebay, Philippe Pierre

    2009-09-01

    This report summarizes existing statistical engines in VTK/Titan and presents the recently parallelized contingency statistics engine. It is a sequel to [PT08] and [BPRT09] which studied the parallel descriptive, correlative, multi-correlative, and principal component analysis engines. The ease of use of this new parallel engines is illustrated by the means of C++ code snippets. Furthermore, this report justifies the design of these engines with parallel scalability in mind; however, the very nature of contingency tables prevent this new engine from exhibiting optimal parallel speed-up as the aforementioned engines do. This report therefore discusses the design trade-offs we made and study performance with up to 200 processors.

  16. Fusion of remote sensing images based on pyramid decomposition with Baldwinian Clonal Selection Optimization

    NASA Astrophysics Data System (ADS)

    Jin, Haiyan; Xing, Bei; Wang, Lei; Wang, Yanyan

    2015-11-01

    In this paper, we put forward a novel fusion method for remote sensing images based on the contrast pyramid (CP) using the Baldwinian Clonal Selection Algorithm (BCSA), referred to as CPBCSA. Compared with classical methods based on the transform domain, the method proposed in this paper adopts an improved heuristic evolutionary algorithm, wherein the clonal selection algorithm includes Baldwinian learning. In the process of image fusion, BCSA automatically adjusts the fusion coefficients of different sub-bands decomposed by CP according to the value of the fitness function. BCSA also adaptively controls the optimal search direction of the coefficients and accelerates the convergence rate of the algorithm. Finally, the fusion images are obtained via weighted integration of the optimal fusion coefficients and CP reconstruction. Our experiments show that the proposed method outperforms existing methods in terms of both visual effect and objective evaluation criteria, and the fused images are more suitable for human visual or machine perception.

  17. The cellular and molecular toxicity of lead in primary and clonal osteoblastic bone cells

    SciTech Connect

    Long, G.J.

    1989-01-01

    First, steady state kinetic models of lead metabolism and calcium homeostasis were developed in both primary and clonal osteoblastic bone cells. Secondly, the effect of lead on cellular calcium homeostasis was determined. Finally, the effect of lead on 1,25 (OH){sub 2}D{sub 3} induced production of osteocalcin, a protein synthesized and secreted by osteoblasts, was investigated. Lead metabolism in osteoblastic bone cells was characterized by three intracellular pools. The largest of these, S{sub 3}, included mitochondrial lead and accounted for 70 percent of total cell lead in primary osteoblastic bone cells and 85 percent of total lead in clonal osteoblastic bone cells. None of the kinetic pools were saturated at lead concentrations up to 100 {mu}M lead. Calcium homeostasis in osteoblastic bone cells was also described by a three compartment, intracellular kinetic model.

  18. Interaction between clonal plasma cells and the immune system in plasma cell dyscrasias.

    PubMed

    Perez-Andres, M; Almeida, J; Martin-Ayuso, M; Moro, M J; Garcia-Marcos, M A; Moreno, I; Dominguez, M; Galende, J; Heras, N; Gonzalez, M I; San Miguel, J F; Orfao, A

    2004-01-01

    The term "monoclonal gammopathy" (MG) includes a group of clonal plasma cell disorders, which show heterogeneous clinical behavior. While multiple myeloma (MM) and plasma cell leukemia (PCL) are incurable malignant diseases, most patients with MG of undetermined significance (MGUS) show an indolent/benign clinical course. Evidence has accumulated which supports the role of the bone marrow microenvironment in MG. Accordingly, the survival, drug-resistance and proliferation of MM cells have been shown to be largely dependent on a supportive microenvironment. Among the different environment-associated parameters, those related to the status/activity of the immune system are particularly relevant. This review focuses on the different ways clonal plasma cells (PC) interact with the immune system in different models of MG, to characterize crucial events in the development and progression of MG. These advances may support the design of novel therapeutic approaches in patients with MG.

  19. Identification of high-risk enterococcal clonal complexes: global dispersion and antibiotic resistance.

    PubMed

    Leavis, Helen L; Bonten, Marc J M; Willems, Rob J L

    2006-10-01

    Vancomycin-resistant Enterococcus faecium spread dramatically in hospital settings in the USA in the 1990s and reached endemicity at the turn of the century. Similarly, rising prevalence rates are currently observed in several European countries, with prevalence rates of greater than 10% reported in seven of these. On the basis of multilocus sequence typing (MLST), the population structure of E. faecium was elucidated and the existence of a distinct high-risk enterococcal clonal complex, designated clonal complex-17 (CC17), which is associated with the majority of hospital outbreaks and clinical infections in five continents, was revealed. This complex is correlated with ampicillin and quinolone resistance and with the presence of a putative pathogenicity island. Preliminary MLST data suggest that similar hospital-adapted complexes might also exist in E. faecalis.

  20. Assessing T cell clonal size distribution: a non-parametric approach.

    PubMed

    Bolkhovskaya, Olesya V; Zorin, Daniil Yu; Ivanchenko, Mikhail V

    2014-01-01

    Clonal structure of the human peripheral T-cell repertoire is shaped by a number of homeostatic mechanisms, including antigen presentation, cytokine and cell regulation. Its accurate tuning leads to a remarkable ability to combat pathogens in all their variety, while systemic failures may lead to severe consequences like autoimmune diseases. Here we develop and make use of a non-parametric statistical approach to assess T cell clonal size distributions from recent next generation sequencing data. For 41 healthy individuals and a patient with ankylosing spondylitis, who undergone treatment, we invariably find power law scaling over several decades and for the first time calculate quantitatively meaningful values of decay exponent. It has proved to be much the same among healthy donors, significantly different for an autoimmune patient before the therapy, and converging towards a typical value afterwards. We discuss implications of the findings for theoretical understanding and mathematical modeling of adaptive immunity.

  1. The impact of clonal mixing on the evolution of social behaviour in aphids.

    PubMed

    Bryden, John; Jansen, Vincent A A

    2010-06-07

    Reports of substantial clonal mixing measured in social aphid colonies seem, on the face of it, to rule out population structure as an explanation of this enigmatic insect's social behaviour. To clarify how selection operates in aphids, and to disentangle direct and indirect fitness components, we present a model of the life cycle of a typical colony-dwelling aphid. The model incorporates ecological factors and includes a trade-off between investing in social behaviour and investing in reproduction. Our focus on inclusive fitness contrasts with previous approaches that optimize colony output. Through deriving a variant of Hamilton's rule, we show that a simple relationship can be established between the patch-carrying capacity and immigration rates into patches. Our results indicate that the levels of clonal mixing reported are not inconsistent with social behaviour. We discuss our model in terms of the evolutionary origins of social behaviour in aphids.

  2. Automated tissue m-FISH analysis workstation for identification of clonally related cells

    NASA Astrophysics Data System (ADS)

    Dubrowski, Piotr; Lam, Wan; Ling, Victor; Lam, Stephen; MacAulay, Calum

    2008-02-01

    We have developed an automated multicolour high-throughput multi-colour Fluorescence in-situ Hybridization (FISH) scanning system for examining Non-Small Cell Lung Cancer (NSCLC) 5-10μm thick tissue specimens and analyzing their FISH spot signals at the individual cell level and then as clonal populations using cell-cell architecture (spatial distributions). Using FISH probes targeting genomic areas deemed significant to chemotherapy resistance, we aim to identify clonal subpopulations of cells in tissue samples likely to be resistant to cis-platinum/vinorelbine chemotherapy. The scanning system consists of automatic image acquisition, cell nuclei segmentation, spot counting and measuring the spatial distribution and connectivity of cells with specific genetic profiles across the entire section using architectural tools to provide the scoring system.

  3. Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis

    PubMed Central

    Inoue, Daichi; Bradley, Robert K.; Abdel-Wahab, Omar

    2016-01-01

    Genomic analyses of the myeloid malignancies and clonal disorders of hematopoiesis that may give rise to these disorders have identified that mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are among the most common targets of somatic mutations. These spliceosomal mutations often occur in a mutually exclusive manner with one another and, in aggregate, account for the most frequent class of mutations in patients with myelodysplastic syndromes (MDSs) in particular. Although substantial progress has been made in understanding the effects of several of these mutations on splicing and splice site recognition, functional connections linking the mechanistic changes in splicing induced by these mutations to the phenotypic consequences of clonal and aberrant hematopoiesis are not yet well defined. This review describes our current understanding of the mechanistic and biological effects of spliceosomal gene mutations in MDSs as well as the regulation of splicing throughout normal hematopoiesis. PMID:27151974

  4. Clonal analysis of childhood acute lymphoblastic leukemia with "cytogenetically independent" cell populations.

    PubMed Central

    Pui, C H; Raskind, W H; Kitchingman, G R; Raimondi, S C; Behm, F G; Murphy, S B; Crist, W M; Fialkow, P J; Williams, D L

    1989-01-01

    Acute lymphoblastic leukemia (ALL) is generally regarded as a clonal disease in which a single abnormal progenitor cell gives rise to neoplastic progeny. Five of 463 cases of childhood ALL with adequately banded leukemic cells were found to have two cytogenetically independent cell populations. In addition, two of the four cases tested had more than two rearranged immunoglobulin genes and (or) T cell receptor genes. To investigate the clonality of these unusual leukemias, we examined the neoplastic cells for X-linked markers extrinsic to the disease. Leukemic cells from each of the three patients heterozygous for an X-linked, restriction fragment length polymorphism showed a single active parental allele, suggesting that both apparently independent cell populations developed from a common progenitor. These cases provide evidence that leukemogenesis involves a multistep process of mutation and suggest that karyotypic abnormalities may be a late event of malignant transformation. Images PMID:2566623

  5. Asymmetric division of clonal muscle stem cells coordinates muscle regeneration in vivo.

    PubMed

    Gurevich, David B; Nguyen, Phong Dang; Siegel, Ashley L; Ehrlich, Ophelia V; Sonntag, Carmen; Phan, Jennifer M N; Berger, Silke; Ratnayake, Dhanushika; Hersey, Lucy; Berger, Joachim; Verkade, Heather; Hall, Thomas E; Currie, Peter D

    2016-07-08

    Skeletal muscle is an example of a tissue that deploys a self-renewing stem cell, the satellite cell, to effect regeneration. Recent in vitro studies have highlighted a role for asymmetric divisions in renewing rare "immortal" stem cells and generating a clonal population of differentiation-competent myoblasts. However, this model currently lacks in vivo validation. We define a zebrafish muscle stem cell population analogous to the mammalian satellite cell and image the entire process of muscle regeneration from injury to fiber replacement in vivo. This analysis reveals complex interactions between satellite cells and both injured and uninjured fibers and provides in vivo evidence for the asymmetric division of satellite cells driving both self-renewal and regeneration via a clonally restricted progenitor pool.

  6. Multi-jet propulsion organized by clonal development in a colonial siphonophore.

    PubMed

    Costello, John H; Colin, Sean P; Gemmell, Brad J; Dabiri, John O; Sutherland, Kelly R

    2015-09-01

    Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labour in thrust and torque production that controls direction and magnitude of whole-colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning, whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but, more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater-distributed propulsion vehicle design.

  7. Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries.

    PubMed

    Mayer, Christian; Jaglin, Xavier H; Cobbs, Lucy V; Bandler, Rachel C; Streicher, Carmen; Cepko, Constance L; Hippenmeyer, Simon; Fishell, Gord

    2015-09-02

    The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.

  8. Multi-jet propulsion organized by clonal development in a colonial siphonophore

    PubMed Central

    Costello, John H.; Colin, Sean P.; Gemmell, Brad J.; Dabiri, John O.; Sutherland, Kelly R.

    2015-01-01

    Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labour in thrust and torque production that controls direction and magnitude of whole-colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning, whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but, more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater-distributed propulsion vehicle design. PMID:26327286

  9. The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer.

    PubMed

    Murchison, Elizabeth P; Tovar, Cesar; Hsu, Arthur; Bender, Hannah S; Kheradpour, Pouya; Rebbeck, Clare A; Obendorf, David; Conlan, Carly; Bahlo, Melanie; Blizzard, Catherine A; Pyecroft, Stephen; Kreiss, Alexandre; Kellis, Manolis; Stark, Alexander; Harkins, Timothy T; Marshall Graves, Jennifer A; Woods, Gregory M; Hannon, Gregory J; Papenfuss, Anthony T

    2010-01-01

    The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.

  10. Development of microsatellite markers for the clonal shrub Orixa japonica (Rutaceae) using 454 sequencing1

    PubMed Central

    Tamaki, Ichiro; Setsuko, Suzuki; Sugai, Kyoko; Yanagisawa, Nao

    2016-01-01

    Premise of the study: Microsatellite markers were developed for a dioecious shrub, Orixa japonica (Rutaceae). Because O. japonica vigorously propagates by vegetative growth, microsatellite markers can be used to identify clonal relationships among its ramets. Methods and Results: Sixteen polymorphic microsatellite markers were identified by 454 next-generation sequencing. The number of alleles and expected heterozygosity for each locus among four populations ranged from two to 10 and from 0.140 to 0.875, respectively. Five of the 16 loci showed a low null allele frequency. Because Orixa is a monotypic genus, cross-amplification in a consubfamilial species, Skimmia japonica, was tested, and only one locus showed polymorphism. Conclusions: These microsatellite markers developed for O. japonica contribute to clone identification for studies examining the clonal structure and true sex ratio in the wild. Moreover, five markers that have a low null allele frequency can also be used for estimating mating systems or performing parentage analysis. PMID:27785383

  11. Multi-jet propulsion organized by clonal development in a colonial siphonophore

    NASA Astrophysics Data System (ADS)

    Costello, John; Colin, Sean; Gemmell, Brad; Dabiri, John; Sutherland, Kelly

    2015-11-01

    Physonect siphonophores are colonial cnidarians that are pervasive predators in many neritic and oceanic ecosystems. Physonects employ multiple, clonal medusan individuals, termed nectophores, to propel an aggregate colony. Here we show that developmental differences between clonal nectophores of the physonect Nanomia bijuga produce a division of labor in thrust and torque production that controls direction and magnitude of whole colony swimming. Although smaller and less powerful, the position of young nectophores near the apex of the nectosome allows them to dominate torque production for turning whereas older, larger and more powerful individuals near the base of the nectosome contribute predominantly to forward thrust production. The patterns we describe offer insight into the biomechanical success of an ecologically important and widespread colonial animal group, but more broadly, provide basic physical understanding of a natural solution to multi-engine organization that may contribute to the expanding field of underwater distributed propulsion vehicle design.

  12. Characterization of Clonality of Epstein-Barr Virus-Induced Human B Lymphoproliferative Disease in Mice with Severe Combined Immunodeficiency

    PubMed Central

    Nakamine, Hirokazu; Masih, Aneal S.; Okano, Motohiko; Taguchi, Yuichi; Pirruccello, Samuel J.; Davis, Jack R.; Mahloch, Mark L.; Beisel, Kirk W.; Kleveland, Kimberly; Sanger, Warren G.; Purtilo, David T.

    1993-01-01

    To improve the diagnostic accuracy and understanding of the pathogenesis of lymphoproliferative diseases (LPDs) occurring in immunosuppressed transplant recipients (post-transplantation LPD), clonality of Epstein-Barr virus-induced human LPDs in mice with severe combined immunodeficiency was examined by analyzing: 1) human immunoglobulin genes and their products, 2) the clonality of Epstein-Barr virus DNA, and 3) genetic alteration of c-myc or bcl-2 genes. A spectrum of clonality was found in the LPDs comparable with that reported for post-transplantation LPDs, although rearrangements of c-myc or bcl-2 genes were not detected. It is confirmed that this system is useful in terms of clonality for understanding the early phases in the pathogenesis of post-transplantation LPD or LPD in immune deficient patients. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:8380952

  13. Parallel NPARC: Implementation and Performance

    NASA Technical Reports Server (NTRS)

    Townsend, S. E.

    1996-01-01

    Version 3 of the NPARC Navier-Stokes code includes support for large-grain (block level) parallelism using explicit message passing between a heterogeneous collection of computers. This capability has the potential for significant performance gains, depending upon the block data distribution. The parallel implementation uses a master/worker arrangement of processes. The master process assigns blocks to workers, controls worker actions, and provides remote file access for the workers. The processes communicate via explicit message passing using an interface library which provides portability to a number of message passing libraries, such as PVM (Parallel Virtual Machine). A Bourne shell script is used to simplify the task of selecting hosts, starting processes, retrieving remote files, and terminating a computation. This script also provides a simple form of fault tolerance. An analysis of the computational performance of NPARC is presented, using data sets from an F/A-18 inlet study and a Rocket Based Combined Cycle Engine analysis. Parallel speedup and overall computational efficiency were obtained for various NPARC run parameters on a cluster of IBM RS6000 workstations. The data show that although NPARC performance compares favorably with the estimated potential parallelism, typical data sets used with previous versions of NPARC will often need to be reblocked for optimum parallel performance. In one of the cases studied, reblocking increased peak parallel speedup from 3.2 to 11.8.

  14. Parallel processing and expert systems

    NASA Technical Reports Server (NTRS)

    Lau, Sonie; Yan, Jerry C.

    1991-01-01

    Whether it be monitoring the thermal subsystem of Space Station Freedom, or controlling the navigation of the autonomous rover on Mars, NASA missions in the 1990s cannot enjoy an increased level of autonomy without the efficient implementation of expert systems. Merely increasing the computational speed of uniprocessors may not be able to guarantee that real-time demands are met for larger systems. Speedup via parallel processing must be pursued alongside the optimization of sequential implementations. Prototypes of parallel expert systems have been built at universities and industrial laboratories in the U.S. and Japan. The state-of-the-art research in progress related to parallel execution of expert systems is surveyed. The survey discusses multiprocessors for expert systems, parallel languages for symbolic computations, and mapping expert systems to multiprocessors. Results to date indicate that the parallelism achieved for these systems is small. The main reasons are (1) the body of knowledge applicable in any given situation and the amount of computation executed by each rule firing are small, (2) dividing the problem solving process into relatively independent partitions is difficult, and (3) implementation decisions that enable expert systems to be incrementally refined hamper compile-time optimization. In order to obtain greater speedups, data parallelism and application parallelism must be exploited.

  15. Parallel integer sorting with medium and fine-scale parallelism

    NASA Technical Reports Server (NTRS)

    Dagum, Leonardo

    1993-01-01

    Two new parallel integer sorting algorithms, queue-sort and barrel-sort, are presented and analyzed in detail. These algorithms do not have optimal parallel complexity, yet they show very good performance in practice. Queue-sort designed for fine-scale parallel architectures which allow the queueing of multiple messages to the same destination. Barrel-sort is designed for medium-scale parallel architectures with a high message passing overhead. The performance results from the implementation of queue-sort on a Connection Machine CM-2 and barrel-sort on a 128 processor iPSC/860 are given. The two implementations are found to be comparable in performance but not as good as a fully vectorized bucket sort on the Cray YMP.

  16. EFFICIENT SCHEDULING OF PARALLEL JOBS ON MASSIVELY PARALLEL SYSTEMS

    SciTech Connect

    F. PETRINI; W. FENG

    1999-09-01

    We present buffered coscheduling, a new methodology to multitask parallel jobs in a message-passing environment and to develop parallel programs that can pave the way to the efficient implementation of a distributed operating system. Buffered coscheduling is based on three innovative techniques: communication buffering, strobing, and non-blocking communication. By leveraging these techniques, we can perform effective optimizations based on the global status of the parallel machine rather than on the limited knowledge available locally to each processor. The advantages of buffered coscheduling include higher resource utilization, reduced communication overhead, efficient implementation of low-control strategies and fault-tolerant protocols, accurate performance modeling, and a simplified yet still expressive parallel programming model. Preliminary experimental results show that buffered coscheduling is very effective in increasing the overall performance in the presence of load imbalance and communication-intensive workloads.

  17. Template based parallel checkpointing in a massively parallel computer system

    DOEpatents

    Archer, Charles Jens; Inglett, Todd Alan

    2009-01-13

    A method and apparatus for a template based parallel checkpoint save for a massively parallel super computer system using a parallel variation of the rsync protocol, and network broadcast. In preferred embodiments, the checkpoint data for each node is compared to a template checkpoint file that resides in the storage and that was previously produced. Embodiments herein greatly decrease the amount of data that must be transmitted and stored for faster checkpointing and increased efficiency of the computer system. Embodiments are directed to a parallel computer system with nodes arranged in a cluster with a high speed interconnect that can perform broadcast communication. The checkpoint contains a set of actual small data blocks with their corresponding checksums from all nodes in the system. The data blocks may be compressed using conventional non-lossy data compression algorithms to further reduce the overall checkpoint size.

  18. Remediation of blowouts by clonal plants in Maqu degraded alpine grasslands of northwest China.

    PubMed

    Kang, JianJun; Zhao, WenZhi; Zhao, Ming

    2017-03-01

    The sand-fixation of plants is considered to be the most effective and fundamental measure in desertification control in many arid and semi-arid regions. Carex brunnescens (Carex spp) and Leymus secalinus (Leymus), two perennial clonal herbs native to the Maqu degraded alpine areas of northwest China, are dominant and constructive species in active sand dunes that have excellent adaptability to fix sand dunes found to date. In order to study the ability and mechanism of sandland blowout remediation by two clone plants C. brunnescens and L. secalinus, the artificially emulated blowouts were set up in the populations of two clonal plants in the field. The results showed that both C. brunnescens and L. secalinus produced more new ramets in the artificially emulated blowouts than in the natural conditions, suggesting that the two clonal plants had strong ability in blowouts remediation; while the biomass, number of leaves and height of new ramets in the artificially emulated blowouts were less than in the natural conditions due to the restriction of poor nutrients in the artificially emulated blowouts. The ability of blowouts remediation by C. brunnescens was stronger than L. secalinus, as it generated more new ramets than L. secalinus in the process of blowouts remediation. The new ramets of L. secalinus in the blowouts remediation were mainly generated by the buds in the rhizomes which spread from outside of the blowouts; while those of C. brunnescens were generated both by the buds in the rhizomes which spread from outside, and by the buds in the rhizomes inside which were freed from dormancy in the deeper soil under wind erosion conditions. These findings suggest that through rapid clonal expansion capability, C. brunnescens and L. secalinus exhibited strong ability in blowouts remediation which can be one of the most effective strategies to restore and reconstruct degraded vegetations in Maqu alpine areas of northwest China.

  19. Geographic and habitat origin influence biomass production and storage translocation in the clonal plant Aegopodium podagraria.

    PubMed

    D'Hertefeldt, Tina; Eneström, Johanna M; Pettersson, Lars B

    2014-01-01

    Through physiological integration, clonal plants can support ramets in unfavourable patches, exploit heterogeneously distributed resources and distribute resources that are taken up over large areas. Physiological integration generally increases in adverse conditions, but it is not well known which factors determine the evolution of physiological integration. The aim of this study was to investigate if clonal plants from Southern and Northern populations of the clonal herb Aegopodium podagraria differed in physiological integration in terms of translocation of carbon to the rhizomes, and in biomass production using a reciprocal transplant experiment. Aegopodium podagraria from shaded conditions have been suggested to share more resources than clones from open conditions and therefore, plants from forest and open populations within the Southern and Northern regions were included. The regional growing conditions greatly affected biomass production. Plants grown in North Sweden produced more biomass and allocated more biomass to shoots, while plants grown in South Sweden allocated more biomass to rhizomes. There was a regional origin effect as plants originating from North Sweden produced more biomass in both regions. Within the Northern region, plants from shaded habitats translocated more (14)C to the rhizomes, suggesting more storage there than in plants from open habitats. In addition to genetic differentiation in biomass production between Northern and Southern populations, probably as a response to a shorter growing season in the North, there appeared to be genetic differentiation in physiological integration within the Northern region. This shows that both regional and local conditions need to be taken into account in future studies of genetic differentiation of physiological integration in clonal plants.

  20. B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

    PubMed Central

    Ferraccioli, G F; Sorrentino, D; De Vita, S; Casatta, L; Labombarda, A; Avellini, C; Dolcetti, R; Di Luca, D; Beltrami, C A; Boiocchi, M; Bartoli, E

    1996-01-01

    OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa. Images PMID:8660105

  1. Invasion strategies in clonal aquatic plants: are phenotypic differences caused by phenotypic plasticity or local adaptation?

    PubMed Central

    Riis, Tenna; Lambertini, Carla; Olesen, Birgit; Clayton, John S.; Brix, Hans; Sorrell, Brian K.

    2010-01-01

    Background and Aims The successful spread of invasive plants in new environments is often linked to multiple introductions and a diverse gene pool that facilitates local adaptation to variable environmental conditions. For clonal plants, however, phenotypic plasticity may be equally important. Here the primary adaptive strategy in three non-native, clonally reproducing macrophytes (Egeria densa, Elodea canadensis and Lagarosiphon major) in New Zealand freshwaters were examined and an attempt was made to link observed differences in plant morphology to local variation in habitat conditions. Methods Field populations with a large phenotypic variety were sampled in a range of lakes and streams with different chemical and physical properties. The phenotypic plasticity of the species before and after cultivation was studied in a common garden growth experiment, and the genetic diversity of these same populations was also quantified. Key Results For all three species, greater variation in plant characteristics was found before they were grown in standardized conditions. Moreover, field populations displayed remarkably little genetic variation and there was little interaction between habitat conditions and plant morphological characteristics. Conclusions The results indicate that at the current stage of spread into New Zealand, the primary adaptive strategy of these three invasive macrophytes is phenotypic plasticity. However, while limited, the possibility that genetic diversity between populations may facilitate ecotypic differentiation in the future cannot be excluded. These results thus indicate that invasive clonal aquatic plants adapt to new introduced areas by phenotypic plasticity. Inorganic carbon, nitrogen and phosphorous were important in controlling plant size of E. canadensis and L. major, but no other relationships between plant characteristics and habitat conditions were apparent. This implies that within-species differences in plant size can be explained

  2. Geographic and Habitat Origin Influence Biomass Production and Storage Translocation in the Clonal Plant Aegopodium podagraria

    PubMed Central

    D′Hertefeldt, Tina; Eneström, Johanna M.; Pettersson, Lars B.

    2014-01-01

    Through physiological integration, clonal plants can support ramets in unfavourable patches, exploit heterogeneously distributed resources and distribute resources that are taken up over large areas. Physiological integration generally increases in adverse conditions, but it is not well known which factors determine the evolution of physiological integration. The aim of this study was to investigate if clonal plants from Southern and Northern populations of the clonal herb Aegopodium podagraria differed in physiological integration in terms of translocation of carbon to the rhizomes, and in biomass production using a reciprocal transplant experiment. Aegopodium podagraria from shaded conditions have been suggested to share more resources than clones from open conditions and therefore, plants from forest and open populations within the Southern and Northern regions were included. The regional growing conditions greatly affected biomass production. Plants grown in North Sweden produced more biomass and allocated more biomass to shoots, while plants grown in South Sweden allocated more biomass to rhizomes. There was a regional origin effect as plants originating from North Sweden produced more biomass in both regions. Within the Northern region, plants from shaded habitats translocated more 14C to the rhizomes, suggesting more storage there than in plants from open habitats. In addition to genetic differentiation in biomass production between Northern and Southern populations, probably as a response to a shorter growing season in the North, there appeared to be genetic differentiation in physiological integration within the Northern region. This shows that both regional and local conditions need to be taken into account in future studies of genetic differentiation of physiological integration in clonal plants. PMID:24427305

  3. Infection Efficiency of Four Phytophthora infestans Clonal Lineages and DNA-Based Quantification of Sporangia

    PubMed Central

    Fall, Mamadou Lamine; Tremblay, David Mathieu; Gobeil-Richard, Mélanie; Couillard, Julie; Rocheleau, Hélène; Van der Heyden, Hervé; Lévesque, Camile André; Beaulieu, Carole; Carisse, Odile

    2015-01-01

    The presence and abundance of pathogen inoculum is with host resistance and environmental conditions a key factor in epidemic development. Therefore, several spore-sampling devices have been proposed to monitor pathogen inoculum above fields. However, to make spore sampling more reliable as a management tool and to facilitate its adoption, information on infection efficiency and molecular tools for estimating airborne sporangia concentration are needed. Experiments were thus undertaken in a growth chamber to study the infection efficiency of four clonal lineages of P. infestans (US-8, US-11, US-23, and US-24) by measuring the airborne sporangia concentration and resulting disease intensity. The relationship between the airborne sporangia concentration and the number of lesions per leaf was exponential. For the same concentration, the sporangia of US-23 caused significantly more lesions than the sporangia of the other clonal lineages did. Under optimal conditions, an airborne sporangia concentration of 10 sporangia m−3 for US-23 was sufficient to cause one lesion per leaf, whereas for the other clonal lineages, it took 15 to 25 sporangia m−3 to reach the same disease intensity. However, in terms of diseased leaf area, there was no difference between clonal lineages US-8, US-23 and US-24. Also, a sensitive quantitative real-time polymerase chain reaction (qPCR) tool was developed to quantify P. infestans airborne sporangia with detection sensitivity of one sporangium. The specificity of the qPCR assay was rigorously tested for airborne inoculum and was either similar to, or an improvement on, other published PCR assays. This assay allows rapid and reliable detection and quantification of P. infestans airborne sporangia and thereby, facilitates the implementation of spores-sampling network. PMID:26301826

  4. Genetic variation in fitness within a clonal population of a plant RNA virus

    PubMed Central

    Cervera, Héctor; Elena, Santiago F.

    2016-01-01

    A long-standing observation in evolutionary virology is that RNA virus populations are highly polymorphic, composed by a mixture of genotypes whose abundances in the population depend on complex interaction between fitness differences, mutational coupling and genetic drift. It was shown long ago, though in cell cultures, that most of these genotypes had lower fitness than the population they belong, an observation that explained why single-virion passages turned on Muller’s ratchet while very large population passages resulted in fitness increases in novel environments. Here we report the results of an experiment specifically designed to evaluate in vivo the fitness differences among the subclonal components of a clonal population of the plant RNA virus tobacco etch potyvirus (TEV). Over 100 individual biological subclones from a TEV clonal population well adapted to the natural tobacco host were obtained by infectivity assays on a local lesion host. The replicative fitness of these subclones was then evaluated during infection of tobacco relative to the fitness of large random samples taken from the starting clonal population. Fitness was evaluated at increasing number of days post-inoculation. We found that at early days, the average fitness of subclones was significantly lower than the fitness of the clonal population, thus confirming previous observations that most subclones contained deleterious mutations. However, as the number of days of viral replication increases, population size expands exponentially, more beneficial and compensatory mutations are produced, and selection becomes more effective in optimizing fitness, the differences between subclones and the population disappeared. PMID:27774299

  5. Network intrusion detection by the coevolutionary immune algorithm of artificial immune systems with clonal selection

    NASA Astrophysics Data System (ADS)

    Salamatova, T.; Zhukov, V.

    2017-02-01

    The paper presents the application of the artificial immune systems apparatus as a heuristic method of network intrusion detection for algorithmic provision of intrusion detection systems. The coevolutionary immune algorithm of artificial immune systems with clonal selection was elaborated. In testing different datasets the empirical results of evaluation of the algorithm effectiveness were achieved. To identify the degree of efficiency the algorithm was compared with analogs. The fundamental rules based of solutions generated by this algorithm are described in the article.

  6. Against the odds: complete outcrossing in a monoecious clonal seagrass Posidonia australis (Posidoniaceae)

    PubMed Central

    Sinclair, Elizabeth A.; Gecan, Ilena; Krauss, Siegfried L.; Kendrick, Gary A.

    2014-01-01

    Background and Aims Seagrasses are marine, flowering plants with a hydrophilous pollination strategy. In these plants, successful mating requires dispersal of filamentous pollen grains through the water column to receptive stigmas. Approximately 40 % of seagrass species are monoecious, and therefore little pollen movement is required if inbreeding is tolerated. Outcrossing in these species is further impacted by clonality, which is variable, but can be extensive in large, dense meadows. Despite this, little is known about the interaction between clonal structure, genetic diversity and mating systems in hydrophilous taxa. Methods Polymorphic microsatellite DNA markers were used to characterize genetic diversity, clonal structure, mating system and realized pollen dispersal in two meadows of the temperate, monoecious seagrass, Posidonia australis, in Cockburn Sound, Western Australia. Key Results Within the two sampled meadows, genetic diversity was moderate among the maternal shoots (R = 0·45 and 0·64) and extremely high in the embryos (R = 0·93–0·97). Both meadows exhibited a highly clumping (or phalanx) structure among clones, with spatial autocorrelation analysis showing significant genetic structure among shoots and embryos up to 10–15 m. Outcrossing rates were not significantly different from one. Pollen dispersal distances inferred from paternity assignment averaged 30·8 and 26·8 m, which was larger than the mean clone size (12·8 and 13·8 m). Conclusions These results suggest highly effective movement of pollen in the water column. Despite strong clonal structure and moderate genetic diversity within meadows, hydrophilous pollination is an effective vector for completely outcrossed offspring. The different localized water conditions at each site (highly exposed conditions vs. weak directional flow) appear to have little influence on the success and pattern of successful pollination in the two meadows. PMID:24812250

  7. Light limitation and litter of an invasive clonal plant, Wedelia trilobata, inhibit its seedling recruitment

    PubMed Central

    Qi, Shan-Shan; Dai, Zhi-Cong; Miao, Shi-Li; Zhai, De-Li; Si, Chun-Can; Huang, Ping; Wang, Rui-Ping; Du, Dao-Lin

    2014-01-01

    Background and Aims Invasive clonal plants have two reproduction patterns, namely sexual and vegetative propagation. However, seedling recruitment of invasive clonal plants can decline as the invasion process proceeds. For example, although the invasive clonal Wedelia trilobata (Asteraceae) produces numerous seeds, few seedlings emerge under its dense population canopy in the field. In this study it is hypothesized that light limitation and the presence of a thick layer of its own litter may be the primary factors causing the failure of seedling recruitment for this invasive weed in the field. Methods A field survey was conducted to determine the allocation of resources to sexual reproduction and seedling recruitment in W. trilobata. Seed germination was also determined in the field. Effects of light and W. trilobata leaf extracts on seed germination and seedling growth were tested in the laboratory. Key Results Wedelia trilobata blooms profusely and produces copious viable seeds in the field. However, seedlings of W. trilobata were not detected under mother ramets and few emerged seedlings were found in the bare ground near to populations. In laboratory experiments, low light significantly inhibited seed germination. Leaf extracts also decreased seed germination and inhibited seedling growth, and significant interactions were found between low light and leaf extracts on seed germination. However, seeds were found to germinate in an invaded field after removal of the W. trilobata plant canopy. Conclusions The results indicate that lack of light and the presence of its own litter might be two major factors responsible for the low numbers of W. trilobata seedlings found in the field. New populations will establish from seeds once the limiting factors are eliminated, and seeds can be the agents of long-distance dispersal; therefore, prevention of seed production remains an important component in controlling the spread of this invasive clonal plant. PMID:24825293

  8. Infection Efficiency of Four Phytophthora infestans Clonal Lineages and DNA-Based Quantification of Sporangia.

    PubMed

    Fall, Mamadou Lamine; Tremblay, David Mathieu; Gobeil-Richard, Mélanie; Couillard, Julie; Rocheleau, Hélène; Van der Heyden, Hervé; Lévesque, Camile André; Beaulieu, Carole; Carisse, Odile

    2015-01-01

    The presence and abundance of pathogen inoculum is with host resistance and environmental conditions a key factor in epidemic development. Therefore, several spore-sampling devices have been proposed to monitor pathogen inoculum above fields. However, to make spore sampling more reliable as a management tool and to facilitate its adoption, information on infection efficiency and molecular tools for estimating airborne sporangia concentration are needed. Experiments were thus undertaken in a growth chamber to study the infection efficiency of four clonal lineages of P. infestans (US-8, US-11, US-23, and US-24) by measuring the airborne sporangia concentration and resulting disease intensity. The relationship between the airborne sporangia concentration and the number of lesions per leaf was exponential. For the same concentration, the sporangia of US-23 caused significantly more lesions than the sporangia of the other clonal lineages did. Under optimal conditions, an airborne sporangia concentration of 10 sporangia m-3 for US-23 was sufficient to cause one lesion per leaf, whereas for the other clonal lineages, it took 15 to 25 sporangia m-3 to reach the same disease intensity. However, in terms of diseased leaf area, there was no difference between clonal lineages US-8, US-23 and US-24. Also, a sensitive quantitative real-time polymerase chain reaction (qPCR) tool was developed to quantify P. infestans airborne sporangia with detection sensitivity of one sporangium. The specificity of the qPCR assay was rigorously tested for airborne inoculum and was either similar to, or an improvement on, other published PCR assays. This assay allows rapid and reliable detection and quantification of P. infestans airborne sporangia and thereby, facilitates the implementation of spores-sampling network.

  9. Parallel Architecture For Robotics Computation

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Bejczy, Antal K.

    1990-01-01

    Universal Real-Time Robotic Controller and Simulator (URRCS) is highly parallel computing architecture for control and simulation of robot motion. Result of extensive algorithmic study of different kinematic and dynamic computational problems arising in control and simulation of robot motion. Study led to development of class of efficient parallel algorithms for these problems. Represents algorithmically specialized architecture, in sense capable of exploiting common properties of this class of parallel algorithms. System with both MIMD and SIMD capabilities. Regarded as processor attached to bus of external host processor, as part of bus memory.

  10. Multigrid on massively parallel architectures

    SciTech Connect

    Falgout, R D; Jones, J E

    1999-09-17

    The scalable implementation of multigrid methods for machines with several thousands of processors is investigated. Parallel performance models are presented for three different structured-grid multigrid algorithms, and a description is given of how these models can be used to guide implementation. Potential pitfalls are illustrated when moving from moderate-sized parallelism to large-scale parallelism, and results are given from existing multigrid codes to support the discussion. Finally, the use of mixed programming models is investigated for multigrid codes on clusters of SMPs.

  11. Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.

    PubMed

    Laszewski, M J; Kemp, J D; Goeken, J A; Mitros, F A; Platz, C E; Dick, F R

    1990-09-01

    The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

  12. High frequency of clonal IG and T-cell receptor gene rearrangements in histiocytic and dendritic cell neoplasms

    PubMed Central

    Huang, Wenting; Qiu, Tian; Zeng, Linshu; Zheng, Bo; Ying, Jianming; Feng, Xiaoli

    2016-01-01

    The 2008 World Health Organization (WHO) diagnostic criteria of histiocytic and dendritic cell neoplasms from hematopoietic and lymphoid tissues no longer required the absence of clonal B-cell/T-cell receptor gene rearrangements. It is true that the clonal B-cell/T-cell receptor gene rearrangements have been identified in rare cases of histiocytic and dendritic cell neoplasms, such as those with or following lymphoma/leukemia or in some sporadic histiocytic/dendritic cell sarcomas, but the clonal features of such group of tumor are still not clear. Here we investigated the clonal status of 33 samples including Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma (LCS), follicular dendritic cell sarcoma (FDCS), interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS). Among them, twenty-eight cases were sporadic without current or past lymphoma/leukemia. Three cases were found with a past history of T-cell lymphoma, one case was followed by extraosseous plasmacytoma, and one case was found with diffuse large B-cell lymphoma (DLBCL). Our results showed that there was a high frequency of clonal IG and T-cell receptor gene rearrangements in these cases. Notably, 4 cases of LCH and 2 cases of FDCS showed both B and T cell receptor gene rearrangements concurrently. One case of FDCS synchronous with DLBCL showed identical clonal IGH in both tumor populations and clonal TCRβ in FDCS alone. No matter if the presence of clonal receptor gene rearrangements was associated with the tumor origin or tumorigenesis, it might serve as a novel tumor marker for developing target therapy. PMID:27823979

  13. IOPA: I/O-aware parallelism adaption for parallel programs

    PubMed Central

    Liu, Tao; Liu, Yi; Qian, Chen; Qian, Depei

    2017-01-01

    With the development of multi-/many-core processors, applications need to be written as parallel programs to improve execution efficiency. For data-intensive applications that use multiple threads to read/write files simultaneously, an I/O sub-system can easily become a bottleneck when too many of these types of threads exist; on the contrary, too few threads will cause insufficient resource utilization and hurt performance. Therefore, programmers must pay much attention to parallelism control to find the appropriate number of I/O threads for an application. This paper proposes a parallelism control mechanism named IOPA that can adjust the parallelism of applications to adapt to the I/O capability of a system and balance computing resources and I/O bandwidth. The programming interface of IOPA is also provided to programmers to simplify parallel programming. IOPA is evaluated using multiple applications with both solid state and hard disk drives. The results show that the parallel applications using IOPA can achieve higher efficiency than those with a fixed number of threads. PMID:28278236

  14. Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

    PubMed Central

    Wilson, Todd M.; Maric, Irina; Simakova, Olga; Bai, Yun; Ching Chan, Eunice; Olivares, Nicolas; Carter, Melody; Maric, Dragan; Robyn, Jamie; Metcalfe, Dean D.

    2011-01-01

    Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34+ progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. (Clinicaltrials.gov identifier: NCT00044122, NCT00001756) PMID:21134978

  15. Clonal integration facilitates the colonization of drought environments by plant invaders.

    PubMed

    Lechuga-Lago, Yaiza; Sixto-Ruiz, Marta; Roiloa, Sergio R; González, Luís

    2016-01-01

    Biological invasion represents one of the main threats for biodiversity conservation at the global scale. Identifying the mechanisms underlying the process of biological invasions is a crucial objective in the prediction of scenarios of future invasions and the mitigation of their impacts. In this sense, some plant attributes might better explain the success of invasive plant species than others. Recently, clonal growth has been identified as an attribute that could contribute to the invasiveness of plants. In this experiment, we aim to determine the effect of physiological integration (one of the most striking attributes associated with clonal growth) in the performance (at morphological and physiological levels) of the aggressive invader Carpobrotus edulis, when occupying stressful environments. To achieve this objective we performed a greenhouse experiment in which apical ramets of C. edulis were water-stressed and the connection with the basal ramets was either left intact (physiological integration is allowed) or severed (physiological integration is impeded). Our results show that clonal integration allowed apical ramets to buffer drought stress in terms of photochemical activity, and as a consequence, to increase their growth in comparison with severed apical ramets. Interestingly, this increase in biomass was mainly due to the production of aboveground structures, increasing the spread along the soil surface, and consequently having important implications for the colonization success of new environments by this aggressive invader.

  16. Staphylococcus aureus In Vitro Secretion of Alpha Toxin (hla) Correlates with the Affiliation to Clonal Complexes

    PubMed Central

    Monecke, Stefan; Müller, Elke; Büchler, Joseph; Stieber, Bettina; Ehricht, Ralf

    2014-01-01

    The alpha toxin of Staphylococcus aureus is a pore forming toxin that penetrates host cell membranes causing osmotic swelling, rupture, lysis and subsequently cell death. Haemolysin alpha is toxic to a wide range of different mammalian cells; i.e., neurotoxic, dermonecrotic, haemolytic, and it can cause lethality in a wide variety of animals. In this study, the in vitro alpha toxin production of 648 previously genotyped isolates of S. aureus was measured quantitatively using antibody microarrays. Isolates originated from medical and veterinary settings and were selected in order to represent diverse clonal complexes and defined clinical conditions. Generally, the production of alpha toxin in vitro is related to the clonal complex affiliation. For clonal complexes CC22, CC30, CC45, CC479, CC705 and others, invariably no alpha toxin production was noted under the given in vitro conditions, while others, such as CC1, CC5, CC8, CC15 or CC96 secreted variable or high levels of alpha toxin. There was no correlation between alpha toxin yield and clinical course of the disease, or between alpha toxin yield and host species. PMID:24940872

  17. Protocol for the clonal analysis of NK cell effector functions by multi-parameter flow cytometry.

    PubMed

    Schönberg, Kathrin; Hejazi, Maryam; Uhrberg, Markus

    2012-01-01

    Natural killer (NK) cells provide a first line of defense against viral infections and prepare the ground for subsequent action of virus-specific T cells in a concerted way. Human NK cells use a sophisticated system of inhibitory and stimulatory receptors of the killer cell immunoglobulin-like receptor (KIR) gene family, which are expressed in a clonally distributed manner. Several studies suggest that KIR play a critical role in NK cell-mediated protection against HCV and HIV infection. As each NK cell expresses an individual set of KIR receptors that enables them to sense differences in HLA class I expression, classical measurement of NK cell function by analysis of target cell killing does not enable one to define and isolate the clinically relevant NK cell effector subsets. Here, we have developed a flow cytometry-based protocol to measure cytolytic activity together with KIR expression at a clonal level. Combined analysis of KIR expression in conjunction with cell surface mobilization of CD107 enables precise enumeration of cytolytic NK cells with defined specificity for HLA class I. Moreover, via inclusion of intracellular perforin or alternatively granzyme B, NK cells with deficient loading of cytotoxic granula can be identified. The present protocol enables identification and isolation of cytotoxic NK cells on a clonal level and enables reliable measurement in healthy as well as in pathological settings such as virus infection and hematological disease.

  18. Clonal integration facilitates the colonization of drought environments by plant invaders

    PubMed Central

    Lechuga-Lago, Yaiza; Sixto-Ruiz, Marta; Roiloa, Sergio R.; González, Luís

    2016-01-01

    Biological invasion represents one of the main threats for biodiversity conservation at the global scale. Identifying the mechanisms underlying the process of biological invasions is a crucial objective in the prediction of scenarios of future invasions and the mitigation of their impacts. In this sense, some plant attributes might better explain the success of invasive plant species than others. Recently, clonal growth has been identified as an attribute that could contribute to the invasiveness of plants. In this experiment, we aim to determine the effect of physiological integration (one of the most striking attributes associated with clonal growth) in the performance (at morphological and physiological levels) of the aggressive invader Carpobrotus edulis, when occupying stressful environments. To achieve this objective we performed a greenhouse experiment in which apical ramets of C. edulis were water-stressed and the connection with the basal ramets was either left intact (physiological integration is allowed) or severed (physiological integration is impeded). Our results show that clonal integration allowed apical ramets to buffer drought stress in terms of photochemical activity, and as a consequence, to increase their growth in comparison with severed apical ramets. Interestingly, this increase in biomass was mainly due to the production of aboveground structures, increasing the spread along the soil surface, and consequently having important implications for the colonization success of new environments by this aggressive invader. PMID:27154623

  19. UbC-StarTrack, a clonal method to target the entire progeny of individual progenitors

    PubMed Central

    Figueres-Oñate, María; García-Marqués, Jorge; López-Mascaraque, Laura

    2016-01-01

    Clonal cell analysis defines the potential of single cells and the diversity they can produce. To achieve this, we have developed a novel adaptation of the genetic tracing strategy, UbC-StarTrack, which attributes a specific and unique color-code to single neural precursors, allowing all their progeny to be tracked. We used integrable fluorescent reporters driven by a ubiquitous promoter in PiggyBac-based vectors to achieve inheritable and stable clonal cell labeling. In addition, coupling this to an inducible Cre-LoxP system avoids the expression of non-integrated reporters. To assess the utility of this system, we first analyzed images of combinatorial expression of fluorescent reporters in transfected cells and their progeny. We also validated the efficiency of the UbC-StarTrack to trace cell lineages through in vivo, in vitro and ex vivo strategies. Finally, progenitors located in the lateral ventricles were targeted at embryonic or postnatal stages to determine the diversity of neurons and glia they produce, and their clonal relationships. In this way we demonstrate that UbC-StarTrack can be used to identify all the progeny of a single cell and that it can be employed in a wide range of contexts. PMID:27654510

  20. Multilocus sequence typing analysis of Staphylococcus lugdunensis implies a clonal population structure.

    PubMed

    Chassain, Benoît; Lemée, Ludovic; Didi, Jennifer; Thiberge, Jean-Michel; Brisse, Sylvain; Pons, Jean-Louis; Pestel-Caron, Martine

    2012-09-01

    Staphylococcus lugdunensis is recognized as one of the major pathogenic species within the genus Staphylococcus, even though it belongs to the coagulase-negative group. A multilocus sequence typing (MLST) scheme was developed to study the genetic relationships and population structure of 87 S. lugdunensis isolates from various clinical and geographic sources by DNA sequence analysis of seven housekeeping genes (aroE, dat, ddl, gmk, ldh, recA, and yqiL). The number of alleles ranged from four (gmk and ldh) to nine (yqiL). Allelic profiles allowed the definition of 20 different sequence types (STs) and five clonal complexes. The 20 STs lacked correlation with geographic source. Isolates recovered from hematogenic infections (blood or osteoarticular isolates) or from skin and soft tissue infections did not cluster in separate lineages. Penicillin-resistant isolates clustered mainly in one clonal complex, unlike glycopeptide-tolerant isolates, which did not constitute a distinct subpopulation within S. lugdunensis. Phylogenies from the sequences of the seven individual housekeeping genes were congruent, indicating a predominantly mutational evolution of these genes. Quantitative analysis of the linkages between alleles from the seven loci revealed a significant linkage disequilibrium, thus confirming a clonal population structure for S. lugdunensis. This first MLST scheme for S. lugdunensis provides a new tool for investigating the macroepidemiology and phylogeny of this unusually virulent coagulase-negative Staphylococcus.

  1. Further clonal expansion of T cells upon rechallenge of superantigen staphylococcal enterotoxin A.

    PubMed

    Aoki, Y; Yoshikai, Y

    1997-01-01

    Superantigens are known to induce clonal anergy and/or deletion in reactive T cells peripherally. This study was undertaken to investigate the T-cell status early after exposure to staphylococcal enterotoxin A (SEA) in vivo and in vitro. At the peak of clonal expansion following the administration of 5 microg SEA (i.e., 2 days after the injection), C57BL/6 mice were rechallenged with the same dose of SEA in vivo. The secondary stimulation augmented clonal expansion of the T cells bearing Vbeta3 and Vbeta11 in both CD4+ and CD8+ populations. In vitro restimulation of the spleen cells taken from the SEA-primed mice also induced further expansion of the Vbeta3+ T cells during 2 days of culturing, whereas without restimulation, a marked reduction of Vbeta3+ T cells occurred. The spleen cells from the SEA-primed mice were hyper-reactive to in vitro restimulation with SEA as measured by 3H-TdR uptake on day 1 of culturing, but augmented proliferation leveled off thereafter. By day 3, the values of 3H-TdR uptake were less than 20% of those of the controls in which spleen cells from native mice were stimulated with SEA in vitro. These results suggest that T cells exposed to SEA in vivo are still capable of proliferating upon SEA rechallenge, but subsequently, the proliferation starts to wane.

  2. High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial

    PubMed Central

    Babina, Irina S.; Herrera-Abreu, Maria Teresa; Tarazona, Noelia; Peckitt, Clare; Kilgour, Elaine; Smith, Neil R.; Geh, Catherine; Rooney, Claire; Cutts, Ros; Campbell, James; Ning, Jian; Fenwick, Kerry; Swain, Amanda; Brown, Gina; Chua, Sue; Thomas, Anne; Johnston, Stephen R.D.; Ajaz, Mazhar; Sumpter, Katherine; Gillbanks, Angela; Watkins, David; Chau, Ian; Popat, Sanjay; Cunningham, David; Turner, Nicholas C.

    2017-01-01

    FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal FGFR2 amplification have a high response rate to the selective FGFR inhibitor AZD4547, whereas cancers with subclonal or low-level amplification did not respond. Using cell lines and patient-derived xenograft models, we show that high-level FGFR2 amplification initiates a distinct oncogene addiction phenotype, characterized by FGFR2-mediated transactivation of alternative receptor kinases, bringing PI3K/mTOR signaling under FGFR control. Signaling in low-level FGFR1-amplified cancers is more restricted to MAPK signaling, limiting sensitivity to FGFR inhibition. Finally, we show that circulating tumor DNA screening can identify high-level clonally amplified cancers. Our data provide a mechanistic understanding of the distinct pattern of oncogene addiction seen in highly amplified cancers and demonstrate the importance of clonality in predicting response to targeted therapy. Significance Robust single-agent response to FGFR inhibition is seen only in high-level FGFR-amplified cancers, with copy-number level dictating response to FGFR inhibition in vitro, in vivo, and in the clinic. High-level amplification of FGFR2 is relatively rare in gastric and breast cancers, and we show that screening for amplification in circulating tumor DNA may present a viable strategy to screen patients. PMID:27179038

  3. Genetic diversity in three invasive clonal aquatic species in New Zealand

    PubMed Central

    2010-01-01

    Background Elodea canadensis, Egeria densa and Lagarosiphon major are dioecious clonal species which are invasive in New Zealand and other regions. Unlike many other invasive species, the genetic variation in New Zealand is very limited. Clonal reproduction is often considered an evolutionary dead end, even though a certain amount of genetic divergence may arise due to somatic mutations. The successful growth and establishment of invasive clonal species may be explained not by adaptability but by pre-existing ecological traits that prove advantageous in the new environment. We studied the genetic diversity and population structure in the North Island of New Zealand using AFLPs and related the findings to the number of introductions and the evolution that has occurred in the introduced area. Results Low levels of genetic diversity were found in all three species and appeared to be due to highly homogeneous founding gene pools. Elodea canadensis was introduced in 1868, and its populations showed more genetic structure than those of the more recently introduced of E. densa (1946) and L. major (1950). Elodea canadensis and L. major, however, had similar phylogeographic patterns, in spite of the difference in time since introduction. Conclusions The presence of a certain level of geographically correlated genetic structure in the absence of sexual reproduction, and in spite of random human dispersal of vegetative propagules, can be reasonably attributed to post-dispersal somatic mutations. Direct evidence of such evolutionary events is, however, still insufficient. PMID:20565861

  4. Liver cell adenoma: A case report with clonal analysis and literature review

    PubMed Central

    Gong, Li; Su, Qin; Zhang, Wei; Li, Ai-Ning; Zhu, Shao-Jun; Feng, Ying-Ming

    2006-01-01

    We report a case of liver cell adenoma (LCA) in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin (CK) 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia. PMID:16610069

  5. Clonal fluctuation within the haematopoietic system of mice reconstituted with retrovirus-infected stem cells.

    PubMed Central

    Snodgrass, R; Keller, G

    1987-01-01

    The clonal make-up of the haematopoietic system of mice reconstituted with retrovirus-infected bone marrow cells was analysed at two different points in time following reconstitution. We have found that under these conditions, the haematopoietic system consists of clones that persist throughout the 5 month course of the experiment as well as those which undergo temporal changes. The various changes that we have observed included the appearance of a new clone(s) in all lineages, the loss of a clone from some lineages and the shift in the appearance of a clone from one lineage to another. In addition, we provide evidence which suggests that the clonal make-up of the thymus changes with time; early after reconstitution it consists of many clones, whereas at the later time-points it contains a limited number of predominant clones. These studies document the dramatic clonal changes which occur within the various lineages for a long time following reconstitution and highlight the difficulty in demonstrating lineage-specific stem cells. Images Fig. 2. Fig. 3. Fig. 4. PMID:2832146

  6. Genotyping the clonal structure of a gorgonian coral, Junceella juncea (Anthozoa: Octocorallia), using microsatellite loci

    NASA Astrophysics Data System (ADS)

    Liu, Shang-Yin Vanson; Yu, Hon-Tsen; Fan, Tung-Yung; Dai, Chang-Feng

    2005-11-01

    The identification of different clones is fundamental to the study of population structure among organisms with mixed reproductive modes such as cnidarians. However, due to the low genetic variation of coral mtDNA and contamination by zooxanthellate DNA, very few molecular markers are available for studying the clonal structure of cnidarians. Herein we used four polymorphic loci of microsatellite DNA isolated from a zooxanthellae-free octocoral, Junceella juncea, to study its clonal structure in seven populations collected from three localities in Taiwan. In total, 40 multilocus genotypes were found among 152 colonies, and the number of genotypes (clones) identified in the seven populations ranged from 2 to 16. Each of the 40 multilocus genotypes was restricted to a single population, even where adjacent populations were only 100 m distant. The ratio of observed to expected genotypic diversity (Go:Ge) ranged from 0.217 to 0.650, and Go showed a significant departure from Ge ( p<0.05) at each site indicating that asexual fragmentation may play a major role in the maintenance of established populations. Mean relatedness ( R) values showed that genotypes within reefs were more closely related than those between regions. The results indicate that microsatellites are useful for discerning the clonal structures among and within populations at different spatial scales.

  7. The population structure of Mycobacterium bovis in Great Britain: Clonal expansion

    PubMed Central

    Smith, Noel H.; Dale, James; Inwald, Jacqueline; Palmer, Si; Gordon, Stephen V.; Hewinson, R. Glyn; Smith, John Maynard

    2003-01-01

    We have analyzed 11,500 isolates of Mycobacterium bovis (the cause of tuberculosis in cattle and other mammals) isolated in Great Britain (England, Wales and Scotland)] and characterized by spoligotype. Genetic exchange between cells is rare or absent in strains of the Mycobacterium tuberculosis complex so that, by using spoligotypes, it is possible to recognize “clones” with a recent common ancestor. The distribution of variable numbers of tandem repeats types in the most common clone in the data set is incompatible with random mutation and drift. The most plausible explanation is a series of “clonal expansions,” and this interpretation is supported by the geographical distribution of different genotypes. We suggest that the clonal expansion of a genotype is caused either by the spread of a favorable mutation, together with all other genes present in the ancestral cell in which the mutation occurred, or by the invasion of a novel geographical region by a limited number of genotypes. A similar pattern is observed in M. tuberculosis (the main cause of tuberculosis in humans). The significance of clonal expansion in other bacteria that have recombination is discussed. PMID:14657373

  8. Identification and characterization of an immunophilin expressed during the clonal expansion phase of adipocyte differentiation.

    PubMed Central

    Yeh, W C; Li, T K; Bierer, B E; McKnight, S L

    1995-01-01

    Mouse 3T3-L1 cells differentiate into fat-laden adipocytes in response to a cocktail of adipogenic hormones. This conversion process occurs in two discrete steps. During an early clonal expansion phase, confluent 3T3-L1 cells proliferate and express the products of the beta and delta members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. The cells subsequently arrest mitotic growth, induce the expression of the alpha form of C/EBP, and acquire the morphology of fully differentiated adipocytes. Many of the genes induced during the terminal phase of adipocyte conversion are directly activated by C/EBP alpha, and gratuitous expression of this transcription factor is capable of catalyzing adipose conversion in a number of different cultured cell lines. The genetic program undertaken during the clonal expansion phase of 3T3-L1 differentiation, controlled in part by C/EBP beta and C/EBP delta, is less clearly understood. To study the molecular events occurring during clonal expansion, we have identified mRNAs that selectively accumulate during this phase of adipocyte conversion. One such mRNA encodes an immunophilin hereby designated FKBP51. In this report we provide the initial molecular characterization of FKBP51. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7479941

  9. Characterisation and clonal dissemination of OXA-23-producing Acinetobacter baumannii in Tabriz, northwest Iran.

    PubMed

    Peymani, Amir; Higgins, Paul G; Nahaei, Mohammad-Reza; Farajnia, Safar; Seifert, Harald

    2012-06-01

    The characteristics and molecular epidemiology of carbapenemase genes amongst 68 imipenem-resistant Acinetobacter baumannii isolated from Imam Reza Hospital (Tabriz, Iran) during a 17-month period were studied. All 68 isolates were typed using sequence group-based multiplex polymerase chain reaction (PCR) to compare the clonal relationship of isolates with known international clonal lineages. Repetitive sequence-based PCR was further performed with representative isolates of each clone. PCR and sequencing were performed to detect OXA-type carbapenemases and class 1, 2 and 3 integron genes as well as to confirm the presence of insertion sequence ISAba1 upstream of bla(OXA-23) and bla(OXA-51-like) genes. Sixty-four isolates (94%) belonged to international clone (IC) II, two isolates (3%) belonged to IC I and two isolates (3%) did not belong to known international clones. All isolates carried bla(OXA-51-like), bla(OXA-23) and class 1 integron genes. No other acquired bla(OXA) genes or class 2 or 3 integron genes were detected. Sequence analysis confirmed the presence of bla(OXA-23) as well as the bla(OXA-51-like) variants bla(OXA-66), bla(OXA-69) and bla(OXA-88). ISAba1 was present upstream of the bla(OXA-23) gene in all of the isolates. Clonal spread of OXA-23-producing A. baumannii emphasises the need for appropriate infection control measures to prevent further spread of these multidrug-resistant organisms.

  10. Monitoring clonal evolution and resistance to EGFR blockade in the blood of metastatic colorectal cancer patients

    PubMed Central

    Siravegna, Giulia; Mussolin, Benedetta; Buscarino, Michela; Corti, Giorgio; Cassingena, Andrea; Crisafulli, Giovanni; Ponzetti, Agostino; Cremolini, Chiara; Amatu, Alessio; Lauricella, Calogero; Lamba, Simona; Hobor, Sebastijan; Avallone, Antonio; Valtorta, Emanuele; Rospo, Giuseppe; Medico, Enzo; Motta, Valentina; Antoniotti, Carlotta; Tatangelo, Fabiana; Bellosillo, Beatriz; Veronese, Silvio; Budillon, Alfredo; Montagut, Clara; Racca, Patrizia; Marsoni, Silvia; Falcone, Alfredo; Corcoran, Ryan B.; Di Nicolantonio, Federica; Loupakis, Fotios; Siena, Salvatore; Sartore-Bianchi, Andrea; Bardelli, Alberto

    2016-01-01

    Colorectal cancer (CRC) is a genetic disease governed by clonal evolution1. Genotyping CRC tissue is employed for therapeutic purposes but this approach has significant limitations. A tissue sample represents a single snapshot in time, is subjected to selection bias due to tumor heterogeneity, and can be difficult to obtain. We exploited circulating DNA (ctDNA) to genotype colorectal tumors and track clonal evolution during therapies with the anti-EGFR antibodies cetuximab or panitumumab. We identified genomic alterations in KRAS, NRAS, MET, ERBB2, FLT3, EGFR and MAP2K1 in ctDNA of patients with primary or acquired resistance to EGFR blockade. Mutant RAS clones, which rise in blood during EGFR blockade, decline upon withdrawal of anti-EGFR antibodies indicating that clonal evolution continues beyond clinical progression. Pharmacogenomic analysis of CRC cells, which had acquired resistance to cetuximab, reveals that upon antibody withdrawal KRAS clones decay, while the population regains drug sensitivity. ctDNA profiles of patients who benefit from multiple challenging with anti-EGFR antibodies exhibit pulsatile levels of mutant KRAS. These results reveal that the CRC genome adapts dynamically to intermittent drug schedules and provide a molecular explanation for the efficacy of re-challenge therapies based on EGFR blockade. PMID:26030179

  11. Clonal and territorial development of the pancreas as revealed by eGFP-labelled mouse chimeras.

    PubMed

    Eberhard, Daniel; Jockusch, Harald

    2010-10-01

    The clonal structure of the pancreas was analysed in neonatal and adult mouse chimeras in which one partner displayed cell patches expressing green fluorescent protein (eGFP). Coherent growth during pancreatic histogenesis was suggested by the presence of large eGFP-labelled acinar clusters rather than a scattered distribution of individual labelled acinar cells. The adult chimeric pancreas contained monophenotypic acini, whereas surprisingly 5% of acini in neonates were polyclonal. Monophenotypic acini presumably arose by coherent expansion leading to large 3D patches and may not be monoclonal. Islets of Langerhans were oligoclonal at both ages investigated. The proportion of eGFP positive cells within islets did not correlate with that of the surrounding acinar tissue indicating clonal independence of islets from their neighbourhood. The patterns observed argue against a secondary contribution of blood-borne progenitor/stem cells to the acinar compartment during tissue turnover. The different clonal origins of acini and islets are integrated into a model of pancreatic histogenesis.

  12. Genetic uniformity characterizes the invasive spread of water hyacinth (Eichhornia crassipes), a clonal aquatic plant.

    PubMed

    Zhang, Yuan-Ye; Zhang, Da-Yong; Barrett, Spencer C H

    2010-05-01

    Aquatic plant invasions are often associated with long-distance dispersal of vegetative propagules and prolific clonal reproduction. These reproductive features combined with genetic bottlenecks have the potential to severely limit genetic diversity in invasive populations. To investigate this question we conducted a global scale population genetic survey using amplified fragment length polymorphism markers of the world's most successful aquatic plant invader -Eichhornia crassipes (water hyacinth). We sampled 1140 ramets from 54 populations from the native (South America) and introduced range (Asia, Africa, Europe, North America, Central America and the Caribbean). Although we detected 49 clones, introduced populations exhibited very low genetic diversity and little differentiation compared with those from the native range, and approximately 80% of introduced populations were composed of a single clone. A widespread clone ('W') detected in two Peruvian populations accounted for 70.9% of the individuals sampled and dominated in 74.5% of the introduced populations. However, samples from Bangladesh and Indonesia were composed of different genotypes, implicating multiple introductions to the introduced range. Nine of 47 introduced populations contained clonal diversity suggesting that sexual recruitment occurs in some invasive sites where environmental conditions favour seedling establishment. The global patterns of genetic diversity in E. crassipes likely result from severe genetic bottlenecks during colonization and prolific clonal propagation. The prevalence of the 'W' genotype throughout the invasive range may be explained by stochastic sampling, or possibly because of pre-adaptation of the 'W' genotype to tolerate low temperatures.

  13. Asexuality alone does not explain the success of clonal forms in insects with geographical parthenogenesis.

    PubMed

    Lundmark, Magnus; Saura, Anssi

    2006-12-01

    Asexual forms of invertebrates are relatively common. They are often more successful than their sexual progenitors. Especially in insects, the pattern called geographical parthenogenesis shows that asexuality is important in speciation and ecological adaptation. In geographical parthenogenesis the clones have a wider distribution than the sexual forms they originate from. This indicates that they have a broader niche they may utilize successfully. The cause of this apparent success is, however, hard to come by as the term asexuality covers separate phenomena that are hard to disentangle from the mode of reproduction itself. Asexual insects are often polyploid, of hybrid origin, or both and these phenomena have been argued to explain the distribution patterns better than clonality. In this study we survey the literature on arthropods with geographical parthenogenesis in an attempt to clarify what evidence there is for the different phenomena explaining the success of the clonal forms. We focus on the few species where knowledge of distribution of different ploidy levels allows for a distinction of contributions from different phenomena to be made. Our survey support that asexuality is not the only factor underlying the success of all asexuals. Evidence about the importance of a hybrid origin of the clones is found to be meagre as the origin of clones is unknown in the majority of cases. Asexuality, hybridity and polyploidy are intertwined phenomena that each and all may contribute to the success of clonal taxa. Polyploidy, however, emerges as the most parsimonious factor explaining the success of these asexual invertebrate taxa.

  14. Aneurysmal Lesions of Patients with Abdominal Aortic Aneurysm Contain Clonally Expanded T Cells

    PubMed Central

    Lu, Song; White, John V.; Lin, Wan Lu; Zhang, Xiaoying; Solomides, Charalambos; Evans, Kyle; Ntaoula, Nectaria; Nwaneshiudu, Ifeyinwa; Gaughan, John; Monos, Dimitri S.; Oleszak, Emilia L.

    2014-01-01

    Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1–2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified β-chain TCR transcripts by the nonpalindromic adaptor–PCR/Vβ-specific PCR and/or Vβ-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of β-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that αβ TCR+ T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag–driven T cell disease. PMID:24752442

  15. Infection by the systemic fungus Epichloë glyceriae alters clonal growth of its grass host, Glyceria striata.

    PubMed Central

    Pan, Jean J; Clay, Keith

    2003-01-01

    Parasites and pathogens are hypothesized to change host growth, reproduction and/or behaviour to increase their own transmission. However, studies which clearly demonstrate that parasites or pathogens are directly responsible for changes in hosts are lacking. We previously found that infection by the systemic fungus Epichloë glyceriae was associated with greater clonal growth by its host, Glyceria striata. Whether greater clonal growth resulted directly from pathogen infection or indirectly from increased likelihood of infection for host genotypes with greater clonal growth could not be determined because only naturally infected and uninfected plants were used. In this study, we decoupled infection and host genotype to evaluate the role of pathogen infection on host development and clonal growth. We found that total biomass production did not differ for clones of the same genotype, but infected clones allocated more biomass to clonal growth. Disinfected clones had more tillers and a greater proportion of their biomass in the mother ramet. Infected clones produced fewer tillers but significantly more and longer stolons than disinfected clones. These results support the hypothesis that pathogen infection directly alters host development. Parasite alteration of clonal growth patterns might be advantageous to the persistence and spread of host plants in some ecological conditions. PMID:12908979

  16. Appendix E: Parallel Pascal development system

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The Parallel Pascal Development System enables Parallel Pascal programs to be developed and tested on a conventional computer. It consists of several system programs, including a Parallel Pascal to standard Pascal translator, and a library of Parallel Pascal subprograms. The library includes subprograms for using Parallel Pascal on a parallel system with a fixed degree of parallelism, such as the Massively Parallel Processor, to conveniently manipulate arrays which have dimensions than the hardware. Programs can be conveninetly tested with small sized arrays on the conventional computer before attempting to run on a parallel system.

  17. Parallel hierarchical method in networks

    NASA Astrophysics Data System (ADS)

    Malinochka, Olha; Tymchenko, Leonid

    2007-09-01

    This method of parallel-hierarchical Q-transformation offers new approach to the creation of computing medium - of parallel -hierarchical (PH) networks, being investigated in the form of model of neurolike scheme of data processing [1-5]. The approach has a number of advantages as compared with other methods of formation of neurolike media (for example, already known methods of formation of artificial neural networks). The main advantage of the approach is the usage of multilevel parallel interaction dynamics of information signals at different hierarchy levels of computer networks, that enables to use such known natural features of computations organization as: topographic nature of mapping, simultaneity (parallelism) of signals operation, inlaid cortex, structure, rough hierarchy of the cortex, spatially correlated in time mechanism of perception and training [5].

  18. New NAS Parallel Benchmarks Results

    NASA Technical Reports Server (NTRS)

    Yarrow, Maurice; Saphir, William; VanderWijngaart, Rob; Woo, Alex; Kutler, Paul (Technical Monitor)

    1997-01-01

    NPB2 (NAS (NASA Advanced Supercomputing) Parallel Benchmarks 2) is an implementation, based on Fortran and the MPI (message passing interface) message passing standard, of the original NAS Parallel Benchmark specifications. NPB2 programs are run with little or no tuning, in contrast to NPB vendor implementations, which are highly optimized for specific architectures. NPB2 results complement, rather than replace, NPB results. Because they have not been optimized by vendors, NPB2 implementations approximate the performance a typical user can expect for a portable parallel program on distributed memory parallel computers. Together these results provide an insightful comparison of the real-world performance of high-performance computers. New NPB2 features: New implementation (CG), new workstation class problem sizes, new serial sample versions, more performance statistics.

  19. "Feeling" Series and Parallel Resistances.

    ERIC Educational Resources Information Center

    Morse, Robert A.

    1993-01-01

    Equipped with drinking straws and stirring straws, a teacher can help students understand how resistances in electric circuits combine in series and in parallel. Follow-up suggestions are provided. (ZWH)

  20. Demonstrating Forces between Parallel Wires.

    ERIC Educational Resources Information Center

    Baker, Blane

    2000-01-01

    Describes a physics demonstration that dramatically illustrates the mutual repulsion (attraction) between parallel conductors using insulated copper wire, wooden dowels, a high direct current power supply, electrical tape, and an overhead projector. (WRM)

  1. Parallel programming of industrial applications

    SciTech Connect

    Heroux, M; Koniges, A; Simon, H

    1998-07-21

    In the introductory material, we overview the typical MPP environment for real application computing and the special tools available such as parallel debuggers and performance analyzers. Next, we draw from a series of real applications codes and discuss the specific challenges and problems that are encountered in parallelizing these individual applications. The application areas drawn from include biomedical sciences, materials processing and design, plasma and fluid dynamics, and others. We show how it was possible to get a particular application to run efficiently and what steps were necessary. Finally we end with a summary of the lessons learned from these applications and predictions for the future of industrial parallel computing. This tutorial is based on material from a forthcoming book entitled: "Industrial Strength Parallel Computing" to be published by Morgan Kaufmann Publishers (ISBN l-55860-54).

  2. Distinguishing serial and parallel parsing.

    PubMed

    Gibson, E; Pearlmutter, N J

    2000-03-01

    This paper discusses ways of determining whether the human parser is serial maintaining at most, one structural interpretation at each parse state, or whether it is parallel, maintaining more than one structural interpretation in at least some circumstances. We make four points. The first two counterclaims made by Lewis (2000): (1) that the availability of alternative structures should not vary as a function of the disambiguating material in some ranked parallel models; and (2) that parallel models predict a slow down during the ambiguous region for more syntactically ambiguous structures. Our other points concern potential methods for seeking experimental evidence relevant to the serial/parallel question. We discuss effects of the plausibility of a secondary structure in the ambiguous region (Pearlmutter & Mendelsohn, 1999) and suggest examining the distribution of reaction times in the disambiguating region.

  3. Wotherspoon criteria combined with B cell clonality analysis by advanced polymerase chain reaction technology discriminates covert gastric marginal zone lymphoma from chronic gastritis

    PubMed Central

    Hummel, M; Oeschger, S; Barth, T F E; Loddenkemper, C; Cogliatti, S B; Marx, A; Wacker, H‐H; Feller, A C; Bernd, H‐W; Hansmann, M‐L; Stein, H; Möller, P

    2006-01-01

    Background and aims Gastric mucosa associated lymphoid tissue lymphoma is a well defined B cell lymphoma yet often impossible to distinguish from severe chronic gastritis on morphological grounds alone. Therefore, it was suggested to use the clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by polymerase chain reaction (PCR), as a decisive criterion. However, there is controversy as to whether B cell clonality also exists in chronic gastritis, hence rendering this approach futile at present. Methods An expert panel re‐examined the histology and immunohistochemistry of a total of 97 cases of gastric biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin‐eosin and CD20 immunostainings. In addition, a new and advanced PCR system for detection of clonal IgH gene rearrangements was independently applied in two institutions in each case. Results The overall IgH clonality assessments of both institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal. Conclusions Using advanced PCR technology, clonal gastritis is extremely rare, if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is regarded as suitable for definitively diagnosing gastric marginal zone lymphoma. PMID:16423889

  4. Address tracing for parallel machines

    NASA Technical Reports Server (NTRS)

    Stunkel, Craig B.; Janssens, Bob; Fuchs, W. Kent

    1991-01-01

    Recently implemented parallel system address-tracing methods based on several metrics are surveyed. The issues specific to collection of traces for both shared and distributed memory parallel computers are highlighted. Five general categories of address-trace collection methods are examined: hardware-captured, interrupt-based, simulation-based, altered microcode-based, and instrumented program-based traces. The problems unique to shared memory and distributed memory multiprocessors are examined separately.

  5. Parallel Algorithms for Image Analysis.

    DTIC Science & Technology

    1982-06-01

    8217 _ _ _ _ _ _ _ 4. TITLE (aid Subtitle) S. TYPE OF REPORT & PERIOD COVERED PARALLEL ALGORITHMS FOR IMAGE ANALYSIS TECHNICAL 6. PERFORMING O4G. REPORT NUMBER TR-1180...Continue on reverse side it neceesary aid Identlfy by block number) Image processing; image analysis ; parallel processing; cellular computers. 20... IMAGE ANALYSIS TECHNICAL 6. PERFORMING ONG. REPORT NUMBER TR-1180 - 7. AUTHOR(&) S. CONTRACT OR GRANT NUMBER(s) Azriel Rosenfeld AFOSR-77-3271 9

  6. Debugging in a parallel environment

    SciTech Connect

    Wasserman, H.J.; Griffin, J.H.

    1985-01-01

    This paper describes the preliminary results of a project investigating approaches to dynamic debugging in parallel processing systems. Debugging programs in a multiprocessing environment is particularly difficult because of potential errors in synchronization of tasks, data dependencies, sharing of data among tasks, and irreproducibility of specific machine instruction sequences from one job to the next. The basic methodology involved in predicate-based debuggers is given as well as other desirable features of dynamic parallel debugging. 13 refs.

  7. A Small Number of Phylogenetically Distinct Clonal Complexes Dominate a Coastal Vibrio cholerae Population

    PubMed Central

    Kirchberger, Paul C.; Orata, Fabini D.; Barlow, E. Jed; Kauffman, Kathryn M.; Case, Rebecca J.; Polz, Martin F.

    2016-01-01

    ABSTRACT Vibrio cholerae is a ubiquitous aquatic microbe in temperate and tropical coastal areas. It is a diverse species, with many isolates that are harmless to humans, while others are highly pathogenic. Most notable among them are strains belonging to the pandemic O1/O139 serogroup lineage, which contains the causative agents of cholera. The environmental selective regimes that led to this diversity are key to understanding how pathogens evolve in environmental reservoirs. A local population of V. cholerae and its close relative Vibrio metoecus from a coastal pond and lagoon system was extensively sampled during two consecutive months across four size fractions (480 isolates). In stark contrast to previous studies, the observed population was highly clonal, with 60% of V. cholerae isolates falling into one of five clonal complexes, which varied in abundance in the short temporal scale sampled. V. cholerae clonal complexes had significantly different distributions across size fractions and the two environments sampled, the pond and the lagoon. Sequencing the genomes of 20 isolates representing these five V. cholerae clonal complexes revealed different evolutionary trajectories, with considerable variations in gene content with potential ecological significance. Showing genotypic differentiation and differential spatial distribution, the dominant clonal complexes are likely ecologically divergent. Temporal variation in the relative abundance of these complexes suggests that transient blooms of specific clones could dominate local diversity. IMPORTANCE Vibrio cholerae is commonly found in coastal areas worldwide, with only a single group of this bacterium capable of causing severe cholera outbreaks. However, the potential to evolve the ability to cause disease exists in many strains of this species in its aquatic reservoir. Understanding how pathogenic bacteria evolve requires the study of their natural environments. By extensive sampling in a geographically

  8. Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia

    PubMed Central

    Nadeu, Ferran; Delgado, Julio; Royo, Cristina; Baumann, Tycho; Stankovic, Tatjana; Pinyol, Magda; Jares, Pedro; Navarro, Alba; Martín-García, David; Beà, Sílvia; Salaverria, Itziar; Oldreive, Ceri; Aymerich, Marta; Suárez-Cisneros, Helena; Rozman, Maria; Villamor, Neus; Colomer, Dolors; López-Guillermo, Armando; González, Marcos; Alcoceba, Miguel; Terol, Maria José; Colado, Enrique; Puente, Xose S.; López-Otín, Carlos; Enjuanes, Anna

    2016-01-01

    Genomic studies have revealed the complex clonal heterogeneity of chronic lymphocytic leukemia (CLL). The acquisition and selection of genomic aberrations may be critical to understanding the progression of this disease. In this study, we have extensively characterized the mutational status of TP53, SF3B1, BIRC3, NOTCH1, and ATM in 406 untreated CLL cases by ultra-deep next-generation sequencing, which detected subclonal mutations down to 0.3% allele frequency. Clonal dynamics were examined in longitudinal samples of 48 CLL patients. We identified a high proportion of subclonal mutations, isolated or associated with clonal aberrations. TP53 mutations were present in 10.6% of patients (6.4% clonal, 4.2% subclonal), ATM mutations in 11.1% (7.8% clonal, 1.3% subclonal, 2% germ line mutations considered pathogenic), SF3B1 mutations in 12.6% (7.4% clonal, 5.2% subclonal), NOTCH1 mutations in 21.8% (14.2% clonal, 7.6% subclonal), and BIRC3 mutations in 4.2% (2% clonal, 2.2% subclonal). ATM mutations, clonal SF3B1, and both clonal and subclonal NOTCH1 mutations predicted for shorter time to first treatment irrespective of the immunoglobulin heavy-chain variable-region gene (IGHV) mutational status. Clonal and subclonal TP53 and clonal NOTCH1 mutations predicted for shorter overall survival together with the IGHV mutational status. Clonal evolution in longitudinal samples mainly occurred in cases with mutations in the initial samples and was observed not only after chemotherapy but also in untreated patients. These findings suggest that the characterization of the subclonal architecture and its dynamics in the evolution of the disease may be relevant for the management of CLL patients. PMID:26837699

  9. Efficiency of parallel direct optimization

    NASA Technical Reports Server (NTRS)

    Janies, D. A.; Wheeler, W. C.

    2001-01-01

    Tremendous progress has been made at the level of sequential computation in phylogenetics. However, little attention has been paid to parallel computation. Parallel computing is particularly suited to phylogenetics because of the many ways large computational problems can be broken into parts that can be analyzed concurrently. In this paper, we investigate the scaling factors and efficiency of random addition and tree refinement strategies using the direct optimization software, POY, on a small (10 slave processors) and a large (256 slave processors) cluster of networked PCs running LINUX. These algorithms were tested on several data sets composed of DNA and morphology ranging from 40 to 500 taxa. Various algorithms in POY show fundamentally different properties within and between clusters. All algorithms are efficient on the small cluster for the 40-taxon data set. On the large cluster, multibuilding exhibits excellent parallel efficiency, whereas parallel building is inefficient. These results are independent of data set size. Branch swapping in parallel shows excellent speed-up for 16 slave processors on the large cluster. However, there is no appreciable speed-up for branch swapping with the further addition of slave processors (>16). This result is independent of data set size. Ratcheting in parallel is efficient with the addition of up to 32 processors in the large cluster. This result is independent of data set size. c2001 The Willi Hennig Society.

  10. Architectures for reasoning in parallel

    NASA Technical Reports Server (NTRS)

    Hall, Lawrence O.

    1989-01-01

    The research conducted has dealt with rule-based expert systems. The algorithms that may lead to effective parallelization of them were investigated. Both the forward and backward chained control paradigms were investigated in the course of this work. The best computer architecture for the developed and investigated algorithms has been researched. Two experimental vehicles were developed to facilitate this research. They are Backpac, a parallel backward chained rule-based reasoning system and Datapac, a parallel forward chained rule-based reasoning system. Both systems have been written in Multilisp, a version of Lisp which contains the parallel construct, future. Applying the future function to a function causes the function to become a task parallel to the spawning task. Additionally, Backpac and Datapac have been run on several disparate parallel processors. The machines are an Encore Multimax with 10 processors, the Concert Multiprocessor with 64 processors, and a 32 processor BBN GP1000. Both the Concert and the GP1000 are switch-based machines. The Multimax has all its processors hung off a common bus. All are shared memory machines, but have different schemes for sharing the memory and different locales for the shared memory. The main results of the investigations come from experiments on the 10 processor Encore and the Concert with partitions of 32 or less processors. Additionally, experiments have been run with a stripped down version of EMYCIN.

  11. Efficiency of parallel direct optimization.

    PubMed

    Janies, D A; Wheeler, W C

    2001-03-01

    Tremendous progress has been made at the level of sequential computation in phylogenetics. However, little attention has been paid to parallel computation. Parallel computing is particularly suited to phylogenetics because of the many ways large computational problems can be broken into parts that can be analyzed concurrently. In this paper, we investigate the scaling factors and efficiency of random addition and tree refinement strategies using the direct optimization software, POY, on a small (10 slave processors) and a large (256 slave processors) cluster of networked PCs running LINUX. These algorithms were tested on several data sets composed of DNA and morphology ranging from 40 to 500 taxa. Various algorithms in POY show fundamentally different properties within and between clusters. All algorithms are efficient on the small cluster for the 40-taxon data set. On the large cluster, multibuilding exhibits excellent parallel efficiency, whereas parallel building is inefficient. These results are independent of data set size. Branch swapping in parallel shows excellent speed-up for 16 slave processors on the large cluster. However, there is no appreciable speed-up for branch swapping with the further addition of slave processors (>16). This result is independent of data set size. Ratcheting in parallel is efficient with the addition of up to 32 processors in the large cluster. This result is independent of data set size.

  12. Inter- and intra-cellular mechanism of NF-kB-dependent survival advantage and clonal expansion of radio-resistant cancer cells.

    PubMed

    Yu, Hui; Aravindan, Natarajan; Xu, Ji; Natarajan, Mohan

    2017-02-01

    Understanding the underlying mechanism by which cancer cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into tumor recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 breast cancer cells in response to clinical radiation and the associated coordination of intra- and inter-cellular signaling that orchestrate radio-resistance and tumor relapse/recurrence. Our findings showed that 2 or 10Gy of (137)Cs γ-rays at a dose rate of 1.03Gy/min trigger the activation of nuclear factor kappa B (NF-κB), its DNA-binding activity and recycles its own transcription. NF-κB DNA-binding kinetic analysis demonstrated both sustained and dual phase NF-κB activation with radiation. Gene manipulation approach revealed that radiation triggered NF-κB-mediated TNF-α transcriptional activity. TNF-α blocking approach confirmed that the de novo synthesis and secretion of TNF-α serves as a pre-requisite for the second phase of NF-κB activation and sustained maintenance. Radiation-associated NF-κB-dependent secretion of TNF-α from irradiated cells, in parallel, activates NF-κB in the non-targeted un-irradiated bystander cells. Together, these findings demonstrated that radiation-triggered NF-κB-dependent TNFα secretion is critical for self-sustenance of NF-κB (through autocrine positive feedback signaling) and for coordinating bystander response (through inter-cellular paracrine mechanism) after radiation exposure. Further, the data suggest that this self-sustained NF-κB in the irradiated cells determines radio-resistance, survival advantage and clonal expansion of the tumor cells at the treatment site. Parallel maintenance of NF-ΚB-TNF-α-NF-κB feedback-cycle in the un-irradiated non-targeted bystander cells initiates supportive mechanism for the promotion and progression of surviving tumor cells. Intervening this molecular pathway would help us to

  13. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

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

    2014-02-11

    Endpoint-based parallel data processing in a parallel active messaging interface ('PAMI') of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective opeartion through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  14. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

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

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  15. The economics of parallel trade.

    PubMed

    Danzon, P M

    1998-03-01

    The potential for parallel trade in the European Union (EU) has grown with the accession of low price countries and the harmonisation of registration requirements. Parallel trade implies a conflict between the principle of autonomy of member states to set their own pharmaceutical prices, the principle of free trade and the industrial policy goal of promoting innovative research and development (R&D). Parallel trade in pharmaceuticals does not yield the normal efficiency gains from trade because countries achieve low pharmaceutical prices by aggressive regulation, not through superior efficiency. In fact, parallel trade reduces economic welfare by undermining price differentials between markets. Pharmaceutical R&D is a global joint cost of serving all consumers worldwide; it accounts for roughly 30% of total costs. Optimal (welfare maximising) pricing to cover joint costs (Ramsey pricing) requires setting different prices in different markets, based on inverse demand elasticities. By contrast, parallel trade and regulation based on international price comparisons tend to force price convergence across markets. In response, manufacturers attempt to set a uniform 'euro' price. The primary losers from 'euro' pricing will be consumers in low income countries who will face higher prices or loss of access to new drugs. In the long run, even higher income countries are likely to be worse off with uniform prices, because fewer drugs will be developed. One policy option to preserve price differentials is to exempt on-patent products from parallel trade. An alternative is confidential contracting between individual manufacturers and governments to provide country-specific ex post discounts from the single 'euro' wholesale price, similar to rebates used by managed care in the US. This would preserve differentials in transactions prices even if parallel trade forces convergence of wholesale prices.

  16. Parallel Implicit Algorithms for CFD

    NASA Technical Reports Server (NTRS)

    Keyes, David E.

    1998-01-01

    The main goal of this project was efficient distributed parallel and workstation cluster implementations of Newton-Krylov-Schwarz (NKS) solvers for implicit Computational Fluid Dynamics (CFD.) "Newton" refers to a quadratically convergent nonlinear iteration using gradient information based on the true residual, "Krylov" to an inner linear iteration that accesses the Jacobian matrix only through highly parallelizable sparse matrix-vector products, and "Schwarz" to a domain decomposition form of preconditioning the inner Krylov iterations with primarily neighbor-only exchange of data between the processors. Prior experience has established that Newton-Krylov methods are competitive solvers in the CFD context and that Krylov-Schwarz methods port well to distributed memory computers. The combination of the techniques into Newton-Krylov-Schwarz was implemented on 2D and 3D unstructured Euler codes on the parallel testbeds that used to be at LaRC and on several other parallel computers operated by other agencies or made available by the vendors. Early implementations were made directly in Massively Parallel Integration (MPI) with parallel solvers we adapted from legacy NASA codes and enhanced for full NKS functionality. Later implementations were made in the framework of the PETSC library from Argonne National Laboratory, which now includes pseudo-transient continuation Newton-Krylov-Schwarz solver capability (as a result of demands we made upon PETSC during our early porting experiences). A secondary project pursued with funding from this contract was parallel implicit solvers in acoustics, specifically in the Helmholtz formulation. A 2D acoustic inverse problem has been solved in parallel within the PETSC framework.

  17. A parallel Jacobson-Oksman optimization algorithm. [parallel processing (computers)

    NASA Technical Reports Server (NTRS)

    Straeter, T. A.; Markos, A. T.

    1975-01-01

    A gradient-dependent optimization technique which exploits the vector-streaming or parallel-computing capabilities of some modern computers is presented. The algorithm, derived by assuming that the function to be minimized is homogeneous, is a modification of the Jacobson-Oksman serial minimization method. In addition to describing the algorithm, conditions insuring the convergence of the iterates of the algorithm and the results of numerical experiments on a group of sample test functions are presented. The results of these experiments indicate that this algorithm will solve optimization problems in less computing time than conventional serial methods on machines having vector-streaming or parallel-computing capabilities.

  18. Parallelizing Timed Petri Net simulations

    NASA Technical Reports Server (NTRS)

    Nicol, David M.

    1993-01-01

    The possibility of using parallel processing to accelerate the simulation of Timed Petri Nets (TPN's) was studied. It was recognized that complex system development tools often transform system descriptions into TPN's or TPN-like models, which are then simulated to obtain information about system behavior. Viewed this way, it was important that the parallelization of TPN's be as automatic as possible, to admit the possibility of the parallelization being embedded in the system design tool. Later years of the grant were devoted to examining the problem of joint performance and reliability analysis, to explore whether both types of analysis could be accomplished within a single framework. In this final report, the results of our studies are summarized. We believe that the problem of parallelizing TPN's automatically for MIMD architectures has been almost completely solved for a large and important class of problems. Our initial investigations into joint performance/reliability analysis are two-fold; it was shown that Monte Carlo simulation, with importance sampling, offers promise of joint analysis in the context of a single tool, and methods for the parallel simulation of general Continuous Time Markov Chains, a model framework within which joint performance/reliability models can be cast, were developed. However, very much more work is needed to determine the scope and generality of these approaches. The results obtained in our two studies, future directions for this type of work, and a list of publications are included.

  19. Visualizing Parallel Computer System Performance

    NASA Technical Reports Server (NTRS)

    Malony, Allen D.; Reed, Daniel A.

    1988-01-01

    Parallel computer systems are among the most complex of man's creations, making satisfactory performance characterization difficult. Despite this complexity, there are strong, indeed, almost irresistible, incentives to quantify parallel system performance using a single metric. The fallacy lies in succumbing to such temptations. A complete performance characterization requires not only an analysis of the system's constituent levels, it also requires both static and dynamic characterizations. Static or average behavior analysis may mask transients that dramatically alter system performance. Although the human visual system is remarkedly adept at interpreting and identifying anomalies in false color data, the importance of dynamic, visual scientific data presentation has only recently been recognized Large, complex parallel system pose equally vexing performance interpretation problems. Data from hardware and software performance monitors must be presented in ways that emphasize important events while eluding irrelevant details. Design approaches and tools for performance visualization are the subject of this paper.

  20. Features in Continuous Parallel Coordinates.

    PubMed

    Lehmann, Dirk J; Theisel, Holger

    2011-12-01

    Continuous Parallel Coordinates (CPC) are a contemporary visualization technique in order to combine several scalar fields, given over a common domain. They facilitate a continuous view for parallel coordinates by considering a smooth scalar field instead of a finite number of straight lines. We show that there are feature curves in CPC which appear to be the dominant structures of a CPC. We present methods to extract and classify them and demonstrate their usefulness to enhance the visualization of CPCs. In particular, we show that these feature curves are related to discontinuities in Continuous Scatterplots (CSP). We show this by exploiting a curve-curve duality between parallel and Cartesian coordinates, which is a generalization of the well-known point-line duality. Furthermore, we illustrate the theoretical considerations. Concluding, we discuss relations and aspects of the CPC's/CSP's features concerning the data analysis.

  1. PARAVT: Parallel Voronoi tessellation code

    NASA Astrophysics Data System (ADS)

    González, R. E.

    2016-10-01

    In this study, we present a new open source code for massive parallel computation of Voronoi tessellations (VT hereafter) in large data sets. The code is focused for astrophysical purposes where VT densities and neighbors are widely used. There are several serial Voronoi tessellation codes, however no open source and parallel implementations are available to handle the large number of particles/galaxies in current N-body simulations and sky surveys. Parallelization is implemented under MPI and VT using Qhull library. Domain decomposition takes into account consistent boundary computation between tasks, and includes periodic conditions. In addition, the code computes neighbors list, Voronoi density, Voronoi cell volume, density gradient for each particle, and densities on a regular grid. Code implementation and user guide are publicly available at https://github.com/regonzar/paravt.

  2. Parallel integrated frame synchronizer chip

    NASA Technical Reports Server (NTRS)

    Ghuman, Parminder Singh (Inventor); Solomon, Jeffrey Michael (Inventor); Bennett, Toby Dennis (Inventor)

    2000-01-01

    A parallel integrated frame synchronizer which implements a sequential pipeline process wherein serial data in the form of telemetry data or weather satellite data enters the synchronizer by means of a front-end subsystem and passes to a parallel correlator subsystem or a weather satellite data processing subsystem. When in a CCSDS mode, data from the parallel correlator subsystem passes through a window subsystem, then to a data alignment subsystem and then to a bit transition density (BTD)/cyclical redundancy check (CRC) decoding subsystem. Data from the BTD/CRC decoding subsystem or data from the weather satellite data processing subsystem is then fed to an output subsystem where it is output from a data output port.

  3. Fast data parallel polygon rendering

    SciTech Connect

    Ortega, F.A.; Hansen, C.D.

    1993-09-01

    This paper describes a parallel method for polygonal rendering on a massively parallel SIMD machine. This method, based on a simple shading model, is targeted for applications which require very fast polygon rendering for extremely large sets of polygons such as is found in many scientific visualization applications. The algorithms described in this paper are incorporated into a library of 3D graphics routines written for the Connection Machine. The routines are implemented on both the CM-200 and the CM-5. This library enables a scientists to display 3D shaded polygons directly from a parallel machine without the need to transmit huge amounts of data to a post-processing rendering system.

  4. Massively Parallel MRI Detector Arrays

    PubMed Central

    Keil, Boris; Wald, Lawrence L

    2013-01-01

    Originally proposed as a method to increase sensitivity by extending the locally high-sensitivity of small surface coil elements to larger areas, the term parallel imaging now includes the use of array coils to perform image encoding. This methodology has impacted clinical imaging to the point where many examinations are performed with an array comprising multiple smaller surface coil elements as the detector of the MR signal. This article reviews the theoretical and experimental basis for the trend towards higher channel counts relying on insights gained from modeling and experimental studies as well as the theoretical analysis of the so-called “ultimate” SNR and g-factor. We also review the methods for optimally combining array data and changes in RF methodology needed to construct massively parallel MRI detector arrays and show some examples of state-of-the-art for highly accelerated imaging with the resulting highly parallel arrays. PMID:23453758

  5. Parallel Adaptive Mesh Refinement Library

    NASA Technical Reports Server (NTRS)

    Mac-Neice, Peter; Olson, Kevin

    2005-01-01

    Parallel Adaptive Mesh Refinement Library (PARAMESH) is a package of Fortran 90 subroutines designed to provide a computer programmer with an easy route to extension of (1) a previously written serial code that uses a logically Cartesian structured mesh into (2) a parallel code with adaptive mesh refinement (AMR). Alternatively, in its simplest use, and with minimal effort, PARAMESH can operate as a domain-decomposition tool for users who want to parallelize their serial codes but who do not wish to utilize adaptivity. The package builds a hierarchy of sub-grids to cover the computational domain of a given application program, with spatial resolution varying to satisfy the demands of the application. The sub-grid blocks form the nodes of a tree data structure (a quad-tree in two or an oct-tree in three dimensions). Each grid block has a logically Cartesian mesh. The package supports one-, two- and three-dimensional models.

  6. Hybrid parallel programming with MPI and Unified Parallel C.

    SciTech Connect

    Dinan, J.; Balaji, P.; Lusk, E.; Sadayappan, P.; Thakur, R.; Mathematics and Computer Science; The Ohio State Univ.

    2010-01-01

    The Message Passing Interface (MPI) is one of the most widely used programming models for parallel computing. However, the amount of memory available to an MPI process is limited by the amount of local memory within a compute node. Partitioned Global Address Space (PGAS) models such as Unified Parallel C (UPC) are growing in popularity because of their ability to provide a shared global address space that spans the memories of multiple compute nodes. However, taking advantage of UPC can require a large recoding effort for existing parallel applications. In this paper, we explore a new hybrid parallel programming model that combines MPI and UPC. This model allows MPI programmers incremental access to a greater amount of memory, enabling memory-constrained MPI codes to process larger data sets. In addition, the hybrid model offers UPC programmers an opportunity to create static UPC groups that are connected over MPI. As we demonstrate, the use of such groups can significantly improve the scalability of locality-constrained UPC codes. This paper presents a detailed description of the hybrid model and demonstrates its effectiveness in two applications: a random access benchmark and the Barnes-Hut cosmological simulation. Experimental results indicate that the hybrid model can greatly enhance performance; using hybrid UPC groups that span two cluster nodes, RA performance increases by a factor of 1.33 and using groups that span four cluster nodes, Barnes-Hut experiences a twofold speedup at the expense of a 2% increase in code size.

  7. Detection of Clonally Expanded Hepatocytes in Chimpanzees with Chronic Hepatitis B Virus Infection ▿ †

    PubMed Central

    Mason, William S.; Low, Huey-Chi; Xu, Chunxiao; Aldrich, Carol E.; Scougall, Catherine A.; Grosse, Arend; Clouston, Andrew; Chavez, Deborah; Litwin, Samuel; Peri, Suraj; Jilbert, Allison R.; Lanford, Robert E.

    2009-01-01

    During a hepadnavirus infection, viral DNA integrates at a low rate into random sites in the host DNA, producing unique virus-cell junctions detectable by inverse nested PCR (invPCR). These junctions serve as genetic markers of individual hepatocytes, providing a means to detect their subsequent proliferation into clones of two or more hepatocytes. A previous study suggested that the livers of 2.4-year-old woodchucks (Marmota monax) chronically infected with woodchuck hepatitis virus contained at least 100,000 clones of >1,000 hepatocytes (W. S. Mason, A. R. Jilbert, and J. Summers, Proc. Natl. Acad. Sci. USA 102:1139-1144, 2005). However, possible correlations between sites of viral-DNA integration and clonal expansion could not be explored because the woodchuck genome has not yet been sequenced. In order to further investigate this issue, we looked for similar clonal expansion of hepatocytes in the livers of chimpanzees chronically infected with hepatitis B virus (HBV). Liver samples for invPCR were collected from eight chimpanzees chronically infected with HBV for at least 20 years. Fifty clones ranging in size from ∼35 to 10,000 hepatocytes were detected using invPCR in 32 liver biopsy fragments (∼1 mg) containing, in total, ∼3 × 107 liver cells. Based on searching the analogous human genome, integration sites were found on all chromosomes except Y, ∼30% in known or predicted genes. However, no obvious association between the extent of clonal expansion and the integration site was apparent. This suggests that the integration site per se is not responsible for the outgrowth of large clones of hepatocytes. PMID:19535448

  8. Clonal types of Toxoplasma gondii among immune compromised and immune competent individuals in Accra, Ghana.

    PubMed

    Ayi, Irene; Kwofie, Kofi Dadzie; Blay, Emmanuel Awusah; Osei, Joseph Harold Nyarko; Frempong, Kwadwo Kyeremeh; Koku, Roberta; Ghansah, Anita; Lartey, Margaret; Suzuki, Takashi; Boakye, Daniel Adjei; Koram, Kwadwo Ansah; Ohta, Nobuo

    2016-06-01

    There are three major clonal lineages, types I, II, and III, of Toxoplasma gondii known to cause human toxoplasmosis worldwide. Toxoplasma gondii infections have, however, not been genotyped in Ghana. This study detected the clonal types infecting immune compromised and immune competent individuals in Accra, Ghana. Blood samples were obtained from 148 HIV seropositive pre-antiretroviral therapy individuals (0 ≤ CD4(+) T-cell count/μl blood ≤ 200) at the Fevers Unit and 149 HIV seronegative apparently healthy blood donors at the blood bank, all of the Korle-Bu Teaching Hospital. Genomic DNA was extracted and multilocus genotyping conducted by nested PCR-RFLP analysis using GRA6, SAG3, and BTUB gene markers. Among the HIV seropositive participants, 54.7% (81/148) were T. gondii DNA positive for any of the markers. Out of the 81, 42.0% (34) were positive for SAG3 only, 30.9% (25) for GRA6 only, 24.7% (20) for both SAG3 and GRA6, and 2.5% (2) for SAG3, GRA6, and BTUB. Overall, 93.8% of the positives were of clonal type II, 1.2% type I, while 4.9% (4) were atypical or mixed types (I and II). In the healthy blood donors, prevalence of T. gondii DNA positivity was 3.4% (5/149) by SAG3 and/or GRA6; among them, 60.0% (3/5) were type I, and the remaining 40.0%, type II. This study showed a relatively high prevalence of active T. gondii infections in immune compromised patients and low prevalence in immune competent individuals in Accra. Type II was highly prevalent. Detection of T. gondii in blood donors raises public health concerns and screening for T. gondii should be considered.

  9. Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

    PubMed Central

    Jones, Rhiannon E.; Rowson, Jan; Grimstead, Julia W.; Keith, W. Nicol; Jenkins, Gareth J. S.

    2017-01-01

    Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia. PMID:28362812

  10. Defense signaling among interconnected ramets of a rhizomatous clonal plant, induced by jasmonic-acid application

    NASA Astrophysics Data System (ADS)

    Chen, Jin-Song; Lei, Ning-Fei; Liu, Qing

    2011-07-01

    Resource sharing between ramets of clonal plants is a well-known phenomenon that allows stoloniferous and rhizomatous species to internally transport water, mineral nutrients and carbohydrates from sites of high supply to sites of high demand. Moreover, vascular ramet connections are likely to provide an excellent means to share substances other than resources, such as defense signals. In a greenhouse experiment, the rhizomatous sedge Carex alrofusca, consisting of integrated ramets of different ages, was used to study the transmission of defense signals through belowground rhizome connections in response to local spray with jasmonic-acid. A feeding preference test with the caterpillar Gynaephora rnenyuanensis was employed to assess benefits of rhizome connections on defense signaling. Young ramets were more responsive to jasmonic-acid treatment than middle-aged or old ramets. Condensed tannin content in the foliage of young ramets showed a significant increase and soluble carbohydrate and nitrogen content showed marginally significant decreases in the 1 mM jasmonic-acid treatment but not in control and/or 0.0001 mM jasmonic-acid treatments. The caterpillar G. rnenyuanensis preferentially grazed young ramets. After a localized spray of 1 mM jasmonic-acid, the leaf area of young ramets consumed by herbivores was greatly reduced. We propose that defense signals may be transmitted through physical connections (stolon or rhizome) among interconnected ramets of clonal plants. Induced resistance to herbivory may selectively enhance the protection of more vulnerable and valuable plant tissues and confer a significant benefit to clonal plants by a modular risk-spreading strategy, equalizing ontogenetic differences of unevenly-aged ramets in chemical defense compounds and nutritional properties of tissue.

  11. Physiological integration ameliorates negative effects of drought stress in the clonal herb Fragaria orientalis.

    PubMed

    Zhang, Yunchun; Zhang, Qiaoying; Sammul, Marek

    2012-01-01

    Clonal growth allows plants to spread horizontally and to establish ramets in sites of contrasting resource status. If ramets remain physiologically integrated, clones in heterogeneous environments can act as cooperative systems--effects of stress on one ramet can be ameliorated by another connected ramet inhabiting benign conditions. But little is known about the effects of patch contrast on physiological integration of clonal plants and no study has addressed its effects on physiological traits like osmolytes, reactive oxygen intermediates and antioxidant enzymes. We examined the effect of physiological integration on survival, growth and stress indicators such as osmolytes, reactive oxygen intermediates (ROIs) and antioxidant enzymes in a clonal plant, Fragaria orientalis, growing in homogenous and heterogeneous environments differing in patch contrast of water availability (1 homogeneous (no contrast) group; 2 low contrast group; 3 high contrast group). Drought stress markedly reduced the survival and growth of the severed ramets of F. orientalis, especially in high contrast treatments. Support from a ramet growing in benign patch considerably reduced drought stress and enhanced growth of ramets in dry patches. The larger the contrast between water availability, the larger the amount of support the depending ramet received from the supporting one. This support strongly affected the growth of the supporting ramet, but not to an extent to cause increase in stress indicators. We also found indication of costs related to maintenance of physiological connection between ramets. Thus, the net benefit of physiological integration depends on the environment and integration between ramets of F. orientalis could be advantageous only in heterogeneous conditions with a high contrast.

  12. Long telomeres are associated with clonality in wild populations of the fissiparous starfish Coscinasterias tenuispina

    PubMed Central

    Garcia-Cisneros, A; Pérez-Portela, R; Almroth, B C; Degerman, S; Palacín, C; Sköld, H Nilsson

    2015-01-01

    Telomeres usually shorten during an organism's lifespan and have thus been used as an aging and health marker. When telomeres become sufficiently short, senescence is induced. The most common method of restoring telomere length is via telomerase reverse transcriptase activity, highly expressed during embryogenesis. However, although asexual reproduction from adult tissues has an important role in the life cycles of certain species, its effect on the aging and fitness of wild populations, as well as its implications for the long-term survival of populations with limited genetic variation, is largely unknown. Here we compare relative telomere length of 58 individuals from four populations of the asexually reproducing starfish Coscinasterias tenuispina. Additionally, 12 individuals were used to compare telomere lengths in regenerating and non-regenerating arms, in two different tissues (tube feet and pyloric cecum). The level of clonality was assessed by genotyping the populations based on 12 specific microsatellite loci and relative telomere length was measured via quantitative PCR. The results revealed significantly longer telomeres in Mediterranean populations than Atlantic ones as demonstrated by the Kruskal–Wallis test (K=24.17, significant value: P-value<0.001), with the former also characterized by higher levels of clonality derived from asexual reproduction. Telomeres were furthermore significantly longer in regenerating arms than in non-regenerating arms within individuals (pyloric cecum tissue: Mann–Whitney test, V=299, P-value<10−6; and tube feet tissue Student's t=2.28, P-value=0.029). Our study suggests that one of the mechanisms responsible for the long-term somatic maintenance and persistence of clonal populations is telomere elongation. PMID:25990879

  13. Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds

    PubMed Central

    Getz, Wayne M.; Salter, Richard; Lyons, Andrew J.; Sippl-Swezey, Nicolas

    2015-01-01

    We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals’ foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual’s biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals

  14. Clonal Diversity of Nosocomial Epidemic Acinetobacter baumannii Strains Isolated in Spain▿

    PubMed Central

    Villalón, Pilar; Valdezate, Sylvia; Medina-Pascual, Maria J.; Rubio, Virginia; Vindel, Ana; Saez-Nieto, Juan A.

    2011-01-01

    Acinetobacter baumannii is one of the major pathogens involved in nosocomial outbreaks. The clonal diversity of 729 epidemic strains isolated from 19 Spanish hospitals (mainly from intensive care units) was analyzed over an 11-year period. Pulsed-field gel electrophoresis (PFGE) identified 58 PFGE types that were subjected to susceptibility testing, rpoB gene sequencing, and multilocus sequence typing (MLST). All PFGE types were multidrug resistant; colistin was the only agent to which all pathogens were susceptible. The 58 PFGE types were grouped into 16 clones based on their genetic similarity (cutoff of 80%). These clones were distributed into one major cluster (cluster D), three medium clusters (clusters A, B, and C), and three minor clusters (clusters E, F, and G). The rpoB gene sequencing and MLST results reflected a clonal distribution, in agreement with the PFGE results. The MLST sequence types (STs) (and their percent distributions) were as follows: ST-2 (47.5%), ST-3 (5.1%), ST-15 (1.7%), ST-32 (1.7%), ST-79 (13.6%), ST-80 (20.3%), and ST-81 (10.2%). ST-79, ST-80, and ST-81 and the alleles cpn60-26 and recA29 are described for the first time. International clones I, II, and III were represented by ST-81, ST-2, and ST-3, respectively. ST-79 and ST-80 could be novel emerging clones. This work confirms PFGE and MLST to be complementary tools in clonality studies. Here PFGE was able to demonstrate the monoclonal pattern of most outbreaks, the inter- and intrahospital transmission of bacteria, and their endemic persistence in some wards. MLST allowed the temporal evolution and spatial distribution of Spanish clones to be monitored and permitted international comparisons to be made. PMID:21177889

  15. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion

    PubMed Central

    Chesnais, Virginie; Renneville, Aline; Toma, Andrea; Lambert, Jérôme; Passet, Marie; Dumont, Florent; Chevret, Sylvie; Lejeune, Julie; Raimbault, Anna; Stamatoullas, Aspasia; Rose, Christian; Beyne-Rauzy, Odile; Delaunay, Jacques; Solary, Eric; Fenaux, Pierre; Dreyfus, François; Preudhomme, Claude; Kosmider, Olivier

    2016-01-01

    Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug’s effects on clonal evolution remain unknown. We investigated recurrent mutations by next-generation sequencing in 94 non-del(5q) MDS patients randomized in the GFM-Len-Epo-08 clinical trial to lenalidomide or lenalidomide plus epoetin β. Clonal evolution was analyzed after 4 cycles of treatment in 42 cases and reanalyzed at later time points in 18 cases. The fate of clonal architecture of single CD34+CD38− hematopoietic stem cells was also determined in 5 cases. Mutation frequency was >10%: SF3B1 (74.5%), TET2 (45.7%), DNMT3A (20.2%), and ASXL1 (19.1%). Analysis of variant allele frequencies indicated a decrease of major mutations in 15 of 20 responders compared with 10 of 22 nonresponders after 4 cycles. The decrease in the variant allele frequency of major mutations was more significant in responders than in nonresponders (P < .001). Genotyping of single CD34+CD38− cell–derived colonies showed that the decrease in the size of dominant subclones could be associated with the rise of founding clones or of hematopoietic stem cells devoid of recurrent mutations. These effects remained transient, and disease escape was associated with the re-emergence of the dominant subclones. In conclusion, we show that, although the drug initially modulates the distribution of subclones, loss of treatment efficacy coincides with the re-expansion of the dominant subclone. This trial was registered at www.clinicaltrials.gov as #NCT01718379. PMID:26626993

  16. Stenotrophomonas maltophilia in Mexico: antimicrobial resistance, biofilm formation and clonal diversity.

    PubMed

    Flores-Treviño, Samantha; Gutiérrez-Ferman, Jessica Lizzeth; Morfín-Otero, Rayo; Rodríguez-Noriega, Eduardo; Estrada-Rivadeneyra, Diego; Rivas-Morales, Catalina; Llaca-Díaz, Jorge M; Camacho-Ortíz, Adrián; Mendoza-Olazarán, Soraya; Garza-González, Elvira

    2014-11-01

    Stenotrophomonas maltophilia is an important multidrug-resistant nosocomial pathogen associated with high mortality. Our aim was to examine antimicrobial susceptibility, biofilm production and clonal relatedness of clinical isolates of S. maltophilia. S. maltophilia isolates were collected between 2006 and 2013 from two tertiary care hospitals in Mexico. Antimicrobial susceptibility was evaluated by the broth microdilution method. PCR was used to determine the presence of β-lactamase genes L1 and L2. Biofilm formation was assessed with crystal violet staining. Clonal relatedness was determined by PFGE. Among the 119 collected S. maltophilia isolates, 73 (61.3%) were from the respiratory tract. Resistance levels exceeded 75% for imipenem, meropenem, ampicillin, aztreonam, gentamicin and tobramycin. Resistance to trimethoprim-sulfamethoxazole was 32.8%. L1 and L2 genes were detected in 77.1% (91/118) and 66.9% (79/118) of isolates, respectively. All S. maltophilia strains were able to produce biofilms. Strains were classified as weak (47.9%, 57/119), moderate (38.7%, 46/119), or strong (13.4%, 16/119) biofilm producers. A total of 89 distinct PFGE types were identified and 21.6% (22/102) of the isolates were distributed in nine clusters. This is the first study in Mexico to reveal characteristics of clinical isolates of S. maltophilia. Clonal diversity data indicate low cross-transmission of S. maltophilia in a hospital setting. The high antibiotic resistance underscores the need for continuous surveillance of S. maltophilia in hospital settings in Mexico.

  17. A predictive relationship between population and genetic sex ratios in clonal species

    NASA Astrophysics Data System (ADS)

    McLetchie, D. Nicholas; García-Ramos, Gisela

    2017-04-01

    Sexual reproduction depends on mate availability that is reflected by local sex ratios. In species where both sexes can clonally expand, the population sex ratio describes the proportion of males, including clonally derived individuals (ramets) in addition to sexually produced individuals (genets). In contrast to population sex ratio that accounts for the overall abundance of the sexes, the genetic sex ratio reflects the relative abundance of genetically unique mates, which is critical in predicting effective population size but is difficult to estimate in the field. While an intuitive positive relationship between population (ramet) sex ratio and genetic (genet) sex ratio is expected, an explicit relationship is unknown. In this study, we determined a mathematical expression in the form of a hyperbola that encompasses a linear to a nonlinear positive relationship between ramet and genet sex ratios. As expected when both sexes clonally have equal number of ramets per genet both sex ratios are identical, and thus ramet sex ratio becomes a linear function of genet sex ratio. Conversely, if sex differences in ramet number occur, this mathematical relationship becomes nonlinear and a discrepancy between the sex ratios amplifies from extreme sex ratios values towards intermediate values. We evaluated our predictions with empirical data that simultaneously quantified ramet and genet sex ratios in populations of several species. We found that the data support the predicted positive nonlinear relationship, indicating sex differences in ramet number across populations. However, some data may also fit the null model, which suggests that sex differences in ramet number were not extensive, or the number of populations was too small to capture the curvature of the nonlinear relationship. Data with lack of fit suggest the presence of factors capable of weakening the positive relationship between the sex ratios. Advantages of this model include predicting genet sex ratio using

  18. Biofilm formation in invasive Staphylococcus aureus isolates is associated with the clonal lineage.

    PubMed

    Naicker, Preneshni R; Karayem, Karayem; Hoek, Kim G P; Harvey, Justin; Wasserman, Elizabeth

    2016-01-01

    The contribution of the genetic background of Staphylococcus aureus to biofilm formation is poorly understood. We investigated the association between the genetic background and the biofilm forming ability of clinical invasive S. aureus isolates. Secondary objectives included investigating any correlation with biofilm formation and methicillin resistance or the source of bacteraemia. The study was conducted at a 1300-bed tertiary hospital in Cape Town, South Africa. S. aureus isolates obtained from blood cultures between January 2010 and January 2012 were included. Genotypic characterization was performed by PFGE, spa typing, SCCmec typing and MLST. Thirty genotypically unique strains were assessed for phenotypic biofilm formation with the microtitre plate assay. All isolates were tested in triplicate and an average optical density, measured at a wavelength of 490 nm, was determined. The biofilm forming ability of isolates with A490 ≤ 0.17 were considered non-adherent, A490 > 0.17 'weak positive' and A490 > 0.34 'strong positive'. Fifty seven percent of isolates formed biofilms. Weak biofilm formation occurred in 40% (n = 12) and strong biofilm formation in 17% (n = 5) of isolates. All 5 isolates capable of strong biofilm formation belong to one spa clonal complex (spa-CC 064). Strains from spa-CC 064 were capable of higher biofilm formation than other spa clonal complexes (p = 0.00002). These 5 strains belonged to MLST CC5 and CC8. Biofilm formation correlates with the spa clonal lineage in our population of invasive S. aureus strains. Biofilm formation did not correlate with methicillin resistance and was not related to the source of bacteraemia.

  19. Understanding the wide geographic range of a clonal perennial grass: plasticity versus local adaptation

    PubMed Central

    Liu, Yanjie; Zhang, Lirong; Xu, Xingliang; Niu, Haishan

    2016-01-01

    Both phenotypic plasticity and local adaptation may allow widely distributed plant species to either acclimate or adapt to environmental heterogeneity. Given the typically low genetic variation of clonal plants across their habitats, phenotypic plasticity may be the primary adaptive strategy allowing them to thrive across a wide range of habitats. In this study, the mechanism supporting the widespread distribution of the clonal plant Leymus chinensis was determined, i.e. phenotypic plasticity or local specialization in water use efficiency (WUE; reflected by foliar δ13C). To test whether plasticity is required for the species to thrive in different habitats, samples were collected across its distribution in the Mongolian steppe, and a controlled watering experiment was conducted with two populations at two different sites. Five populations were also transplanted from different sites into a control environment, and the foliar δ13C was compared between the control and original habitats, to test for local specialization in WUE. Results demonstrated decreased foliar δ13C with increasing precipitation during controlled watering experiments, with divergent responses between the two populations assessed. Change in foliar δ13C (−3.69 ‰) due to water addition was comparable to fluctuations of foliar δ13C observed in situ (−4.83 ‰). Foliar δ13C differed by −0.91 ‰ between two transplanted populations; however, this difference was not apparent between the two populations when growing in their original habitats. Findings provide evidence that local adaptation affects foliar δ13C much less than phenotypic plasticity. Thus, plasticity in WUE is more important than local adaptation in allowing the clonal plant L. chinensis to occupy a wide range of habitats in the Mongolian steppe. PMID:26644341

  20. Phenotypic Responses of a Stoloniferous Clonal Plant Buchloe dactyloides to Scale-Dependent Nutrient Heterogeneity

    PubMed Central

    Han, Lei; Liu, Jun-Xiang; Sun, Zhen-Yuan

    2013-01-01

    Clonal plants could modify phenotypic responses to nutrients heterogeneously distributed both in space and time by physiological integration. It will take times to do phenotypic responses to modifications which are various in different growth periods. An optimal phenotype is reached when there is a match between nutrient conditions and foraging ability. A single plantlet of Buchloe dactyloides with two stolons was transplanted into heterogeneous nutrient conditions. One stolon grew in homogeneous nutrient patch, while the other cultured in different scales of heterogeneous nutrient patches. As compared to the other nutrient treatment, heterogeneous nutrient treatments with small scale of 25×25 cm resulted in a higher biomass, and larger number of ramets, clumps and stolons in B. dactyloides at both genet and clonal fragment levels. Significant differences of number of ramets, clumps and stolons were detected at the rapid growth stage, but not in the early stage of the experiment. Foraging ability was more efficient in heterogeneous than in homogeneous nutrient conditions as assessed by higher root mass and root to shoot ratio. Different nutrient treatments did not prompt significant differences in internode and root length. Physiological integration significantly increased biomass, but did not influence other growth or morphological characters. These results suggest that physiological integration modifies phenotypic plasticity of B. dactyloides for efficient foraging of nutrients in heterogeneous nutrient conditions. These effects are more pronounced at genet and clonal fragment levels when the patch scale is 25×25 cm. Time is a key factor when phenotypic plasticity of B. dactyloides in heterogeneous nutrient conditions is examined. PMID:23826285

  1. Ex Uno Plures: Clonal Reinforcement Drives Evolution of a Simple Microbial Community

    PubMed Central

    Kinnersley, Margie; Wenger, Jared; Kroll, Evgueny; Adams, Julian; Sherlock, Gavin; Rosenzweig, Frank

    2014-01-01

    A major goal of genetics is to define the relationship between phenotype and genotype, while a major goal of ecology is to identify the rules that govern community assembly. Achieving these goals by analyzing natural systems can be difficult, as selective pressures create dynamic fitness landscapes that vary in both space and time. Laboratory experimental evolution offers the benefit of controlling variables that shape fitness landscapes, helping to achieve both goals. We previously showed that a clonal population of E. coli experimentally evolved under continuous glucose limitation gives rise to a genetically diverse community consisting of one clone, CV103, that best scavenges but incompletely utilizes the limiting resource, and others, CV101 and CV116, that consume its overflow metabolites. Because this community can be disassembled and reassembled, and involves cooperative interactions that are stable over time, its genetic diversity is sustained by clonal reinforcement rather than by clonal interference. To understand the genetic factors that produce this outcome, and to illuminate the community's underlying physiology, we sequenced the genomes of ancestral and evolved clones. We identified ancestral mutations in intermediary metabolism that may have predisposed the evolution of metabolic interdependence. Phylogenetic reconstruction indicates that the lineages that gave rise to this community diverged early, as CV103 shares only one Single Nucleotide Polymorphism with the other evolved clones. Underlying CV103's phenotype we identified a set of mutations that likely enhance glucose scavenging and maintain redox balance, but may do so at the expense of carbon excreted in overflow metabolites. Because these overflow metabolites serve as growth substrates that are differentially accessible to the other community members, and because the scavenging lineage shares only one SNP with these other clones, we conclude that this lineage likely served as an

  2. Cutaneous basal cell carcinosarcomas: evidence of clonality and recurrent chromosomal losses.

    PubMed

    Harms, Paul W; Fullen, Douglas R; Patel, Rajiv M; Chang, Dannie; Shalin, Sara C; Ma, Linglei; Wood, Benjamin; Beer, Trevor W; Siddiqui, Javed; Carskadon, Shannon; Wang, Min; Palanisamy, Nallasivam; Fisher, Gary J; Andea, Aleodor

    2015-05-01

    Cutaneous carcinosarcomas are heterogeneous group of tumors composed of malignant epithelial and mesenchymal components. Although mutation analyses have identified clonal changes between these morphologically disparate components in some subtypes of cutaneous carcinosarcoma, few cases have been analyzed thus far. To our knowledge, copy number variations (CNVs) and copy-neutral loss of heterozygosity (CN-LOH) have not been investigated in cutaneous carcinosarcomas. We analyzed 4 carcinosarcomas with basal cell carcinoma and osteosarcomatous components for CNVs/CN-LOH by comparative genomic hybridization/single-nucleotide polymorphism array, TP53 hot spot mutations by polymerase chain reaction and Sanger sequencing, and TP53 genomic rearrangements by fluorescence in situ hybridization. All tumors displayed multiple CNV/CN-LOH events (median, 7.5 per tumor). Three of 4 tumors displayed similar CNV/CN-LOH patterns between the epithelial and mesenchymal components within each tumor, supporting a common clonal origin. Recurrent changes included allelic loss at 9p21 (CDKN2A), 9q (PTCH1), and 17p (TP53). Allelic losses of chromosome 16 including CDH1 (E-cadherin) were present in 2 tumors and were restricted to the sarcomatous component. TP53 mutation analysis revealed an R248L mutation in both epithelial and mesenchymal components of 1 tumor. No TP53 rearrangements were identified. Our findings indicate that basal cell carcinosarcomas harbor CNV/CN-LOH changes similar to conventional basal cell carcinoma, with additional changes including recurrent 9p21 losses and a relatively high burden of copy number changes. In addition, most cutaneous carcinosarcomas show evidence of clonality between epithelial and mesenchymal components.

  3. Molecular genetic evidence for unifocal origin of advanced epithelial ovarian cancer and for minor clonal divergence.

    PubMed Central

    Abeln, E. C.; Kuipers-Dijkshoorn, N. J.; Berns, E. M.; Henzen-Logmans, S. C.; Fleuren, G. J.; Cornelisse, C. J.

    1995-01-01

    Detection of loss of heterozygosity (LOH) and DNA flow cytometry (FCM) were used to trace the origin of bilateral ovarian cancer from 16 patients. From each tumour the DNA index (DI) and LOH patterns for chromosomes 1, 3, 6, 11, 17, 18, 22 and X were determined with 36 microsatellite markers. Formalin-fixed, paraffin-embedded as well as frozen specimens were used. Flow cytometric cell sorting was used to enrich tumour cells for polymerase chain reaction (PCR)-driven LOH analysis. Analysis of the LOH data showed that in 12 of the 16 cases concordance was observed for all informative markers, namely retention of heterozygosity (ROH) or loss of identical alleles in both tumour samples. In four cases discordant LOH patterns were observed. In two cases the discordant LOH was found for one of the chromosomes tested while other LOH patterns clearly indicated a unifocal origin. This suggests limited clonal divergence. In the other two cases all LOH patterns were discordant, most likely indicating an independent origin. The number of chromosomes showing LOH ranged from 0 to 6. Comparison of DNA FCM and the LOH data showed that the latter technique has a higher sensitivity for the detection of a unifocal origin. In 14/16 cases evidence was found for a unifocal origin, while in two cases clonal divergence was found at LOH level and in two other cases clonal divergence at DNA ploidy level. In 12 cases the complete observed allelotype had developed before the formation of metastases, including the two cases showing a large DNA ploidy difference. Images Figure 2 Figure 3 Figure 4 PMID:7577492

  4. Physiological Integration Ameliorates Negative Effects of Drought Stress in the Clonal Herb Fragaria orientalis

    PubMed Central

    Zhang, Yunchun; Zhang, Qiaoying; Sammul, Marek

    2012-01-01

    Clonal growth allows plants to spread horizontally and to establish ramets in sites of contrasting resource status. If ramets remain physiologically integrated, clones in heterogeneous environments can act as cooperative systems – effects of stress on one ramet can be ameliorated by another connected ramet inhabiting benign conditions. But little is known about the effects of patch contrast on physiological integration of clonal plants and no study has addressed its effects on physiological traits like osmolytes, reactive oxygen intermediates and antioxidant enzymes. We examined the effect of physiological integration on survival, growth and stress indicators such as osmolytes, reactive oxygen intermediates (ROIs) and antioxidant enzymes in a clonal plant, Fragaria orientalis, growing in homogenous and heterogeneous environments differing in patch contrast of water availability (1 homogeneous (no contrast) group; 2 low contrast group; 3 high contrast group). Drought stress markedly reduced the survival and growth of the severed ramets of F. orientalis, especially in high contrast treatments. Support from a ramet growing in benign patch considerably reduced drought stress and enhanced growth of ramets in dry patches. The larger the contrast between water availability, the larger the amount of support the depending ramet received from the supporting one. This support strongly affected the growth of the supporting ramet, but not to an extent to cause increase in stress indicators. We also found indication of costs related to maintenance of physiological connection between ramets. Thus, the net benefit of physiological integration depends on the environment and integration between ramets of F. orientalis could be advantageous only in heterogeneous conditions with a high contrast. PMID:22957054

  5. Epidemiological tracking and population assignment of the non-clonal bacterium, Burkholderia pseudomallei.

    PubMed

    Dale, Julia; Price, Erin P; Hornstra, Heidie; Busch, Joseph D; Mayo, Mark; Godoy, Daniel; Wuthiekanun, Vanaporn; Baker, Anthony; Foster, Jeffrey T; Wagner, David M; Tuanyok, Apichai; Warner, Jeffrey; Spratt, Brian G; Peacock, Sharon J; Currie, Bart J; Keim, Paul; Pearson, Talima

    2011-12-01

    Rapid assignment of bacterial pathogens into predefined populations is an important first step for epidemiological tracking. For clonal species, a single allele can theoretically define a population. For non-clonal species such as Burkholderia pseudomallei, however, shared allelic states between distantly related isolates make it more difficult to identify population defining characteristics. Two distinct B. pseudomallei populations have been previously identified using multilocus sequence typing (MLST). These populations correlate with the major foci of endemicity (Australia and Southeast Asia). Here, we use multiple Bayesian approaches to evaluate the compositional robustness of these populations, and provide assignment results for MLST sequence types (STs). Our goal was to provide a reference for assigning STs to an established population without the need for further computational analyses. We also provide allele frequency results for each population to enable estimation of population assignment even when novel STs are discovered. The ability for humans and potentially contaminated goods to move rapidly across the globe complicates the task of identifying the source of an infection or outbreak. Population genetic dynamics of B. pseudomallei are particularly complicated relative to other bacterial pathogens, but the work here provides the ability for broad scale population assignment. As there is currently no independent empirical measure of successful population assignment, we provide comprehensive analytical details of our comparisons to enable the reader to evaluate the robustness of population designations and assignments as they pertain to individual research questions. Finer scale subdivision and verification of current population compositions will likely be possible with genotyping data that more comprehensively samples the genome. The approach used here may be valuable for other non-clonal pathogens that lack simple group-defining genetic characteristics

  6. Medipix2 parallel readout system

    NASA Astrophysics Data System (ADS)

    Fanti, V.; Marzeddu, R.; Randaccio, P.

    2003-08-01

    A fast parallel readout system based on a PCI board has been developed in the framework of the Medipix collaboration. The readout electronics consists of two boards: the motherboard directly interfacing the Medipix2 chip, and the PCI board with digital I/O ports 32 bits wide. The device driver and readout software have been developed at low level in Assembler to allow fast data transfer and image reconstruction. The parallel readout permits a transfer rate up to 64 Mbytes/s. http://medipix.web.cern ch/MEDIPIX/

  7. Gang scheduling a parallel machine

    SciTech Connect

    Gorda, B.C.; Brooks, E.D. III.

    1991-03-01

    Program development on parallel machines can be a nightmare of scheduling headaches. We have developed a portable time sharing mechanism to handle the problem of scheduling gangs of processors. User program and their gangs of processors are put to sleep and awakened by the gang scheduler to provide a time sharing environment. Time quantums are adjusted according to priority queues and a system of fair share accounting. The initial platform for this software is the 128 processor BBN TC2000 in use in the Massively Parallel Computing Initiative at the Lawrence Livermore National Laboratory. 2 refs., 1 fig.

  8. Gang scheduling a parallel machine

    SciTech Connect

    Gorda, B.C.; Brooks, E.D. III.

    1991-12-01

    Program development on parallel machines can be a nightmare of scheduling headaches. We have developed a portable time sharing mechanism to handle the problem of scheduling gangs of processes. User programs and their gangs of processes are put to sleep and awakened by the gang scheduler to provide a time sharing environment. Time quantum are adjusted according to priority queues and a system of fair share accounting. The initial platform for this software is the 128 processor BBN TC2000 in use in the Massively Parallel Computing Initiative at the Lawrence Livermore National Laboratory.

  9. The Complexity of Parallel Algorithms,

    DTIC Science & Technology

    1985-11-01

    Much of this work was done in collaboration with my advisor, Ernst Mayr . He was also supported in part by ONR contract N00014-85-C-0731. F ’. Table...Helinbold and Mayr in their algorithn to compute an optimal two processor schedule [HM2]. One of the promising developments in parallel algorithms is that...lei can be solved by it fast parallel algorithmmmi if the nmlmmmibers are smiall. llehmibold and Mayr JIlM I] have slhowm that. if Ole job timies are

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

    DTIC Science & Technology

    2015-10-01

    ERG-/SPINK1- ERG+/SPINK1- RPA 80% RRP or RP or ERG+/SPINK1- ERG/SPINK1 IHC C H &E H &E ERG/SPINK1 IHC D Figure 1 B Figure 1. Clonal evaluation of...Examples of Hematoxylin and eosin ( H &E) stained and dual ERG/SPINK1 IHC discontinuously involved prostate biopsy cores from two cases are shown. In C , both...SUBJECT TERMS Multiclonality, ERG, SPINK1, immunohistochemistry, active surveillance, prostate biopsy, prostatectomy 16. SECURITY CLASSIFICATION OF: 17

  11. Synapse formation between clonal neuroblastoma X glioma hybrid cells and striated muscle cells.

    PubMed Central

    Nelson, P; Christian, C; Nirenberg, M

    1976-01-01

    Clonal neuroblastoma X glioma hybrid cells were shown to form synapses with cultured, striated muscle cells. The properties of the synapses between hybrid and muscle cells were similar to those of the normal, neuromuscular synapse at an early stage of development. The number of synapses formed and the efficiency of transmission across synapses were found to be regulated, apparently independently, by components in the culture medium. Under appropriate conditions synapses were found with 20% of the hybrid-muscle cell pairs examined; thus, the hybrid cells form synapses with relatively high frequency. Images PMID:1061105

  12. The relative importance of sexual reproduction versus clonal spread in an aridland bunchgrass.

    PubMed

    Liston, A; Wilson, B L; Robinson, W A; Doescher, P S; Harris, N R; Svejcar, T

    2003-10-01

    Festuca idahoensis (Idaho fescue) is a perennial caespitose grass, common in semi-arid rangelands of the Intermountain West. To determine how individuals are recruited into a population, we studied two long-term monitoring plots that were established in 1937 at the Northern Great Basin Experimental Range in southeastern Oregon. The plots measured 3.05x3.05 m, and were located approximately 30 m apart. One plot was ungrazed, the other was subject to moderate levels of cattle grazing. The number of F. idahoensis plants in both plots increased ten-fold between 1937 and 1996, but whether this was due primarily to reproduction by seed or clonal fragmentation was unknown. In 1996, we mapped and sampled 160 plants of F. idahoensis. We used dominant inter-simple sequence repeat (ISSR) markers and codominant allozyme markers in order to identify genetic individuals and measure genetic diversity. Both plots were characterized by high levels of genetic and clonal diversity. When information from ISSRs, allozymes and sample location were combined, 126 genets were recognized, each consisting of one to four samples (ramets). By measuring the diameter of clones surrounding plants that were present in 1937, we estimated that clonal spread occurred at a rate of approximately 3.7 cm per decade, and thus was of secondary importance in the maintenance and increase of F. idahoensis stands. Sexual reproduction, rather than clonal fragmentation, accounted for most of the recruitment of new plants into these plots. The grazed plot had fewer ramets, genotypes, and clones than the ungrazed plot, but the ramets were significantly larger. Levels of genetic diversity did not differ in the grazed and ungrazed plots, but there was some evidence for a small, but significant level of genetic differentiation between the two. The results also indicate that F. idahoensis has the potential to be a long-lived species with some individuals persisting in excess of 60 years. This study demonstrates how

  13. Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

    PubMed Central

    2016-01-01

    Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

  14. Clonal relationship among Vibrio cholerae O1 El Tor strains isolated in Somalia.

    PubMed

    Scrascia, Maria; Pugliese, Nicola; Maimone, Francesco; Mohamud, Kadigia A; Grimont, Patrick A D; Materu, Sadiki F; Pazzani, Carlo

    2009-03-01

    One hundred and three Vibrio cholerae O1 strains, selected to represent the cholera outbreaks which occurred in Somalia in 1998-1999, were characterized by random amplified polymorphic DNA patterns, ribotyping, and antimicrobial susceptibility. All strains showed a unique amplified DNA pattern and 2 closely related ribotypes (B5a and B8a), among which B5a was the more frequently identified. Ninety-one strains were resistant to ampicillin, chloramphenicol, spectinomycin, streptomycin, sulfamethoxazole, and trimethoprim, conferred, except for spectinomycin, by a conjugative plasmid IncC. These findings indicated that the group of strains active in Somalia in the late 1990s had a clonal origin.

  15. Clonal dissemination of multilocus sequence type 11 Klebsiella pneumoniae carbapenemase - producing K. pneumoniae in a Chinese teaching hospital.

    PubMed

    Sun, Kangde; Chen, Xu; Li, Chunsheng; Yu, Zhongmin; Zhou, Qi; Yan, Yuzhong

    2015-02-01

    Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has disseminated rapidly in China. We aimed to analyze the molecular epidemiology of four KPC-producing K. pneumoniae strains isolated from a suspected clonal outbreak during a 3-month period and to track the dissemination of KPC-producing K. pneumonia retrospectively. We created antimicrobial susceptibility profiles using an automated broth microdilution system and broth microdilution methods. We screened carbapenemase and KPC phenotypes using the modified Hodge test and meropenem-boronic acid (BA) disk test, respectively. We identified β-lactamase genes with PCR and sequencing. We investigated clonal relatedness for epidemiological comparison using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates expressed multidrug resistance and yielded positive results for the modified Hodge and meropenem-BA disk tests. The isolates all carried blaKPC -2 , and coproduced CTX-M-type extended-spectrum β-lactamase. PFGE and MLST showed that the isolates were clonally related. The PFGE patterns of these isolates had ≥90% similarity. We found a single clone, sequence type (ST) 11, and its typical dissemination mode resembled clonal spread. The dissemination of KPC-producing K. pneumoniae is clonally related and there is probable local transmission of a successful ST11 clone.

  16. Clonal Evolution Revealed by Whole Genome Sequencing in a Case of Primary Myelofibrosis Transformed to Secondary Acute Myeloid Leukemia

    PubMed Central

    Engle, Elizabeth K.; Fisher, Daniel A.C.; Miller, Christopher A.; McLellan, Michael D.; Fulton, Robert S.; Moore, Deborah M.; Wilson, Richard K.; Ley, Timothy J.; Oh, Stephen T.

    2014-01-01

    Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML. PMID:25252869

  17. Whole-Genome Sequencing of Three Clonal Clinical Isolates of B. cenocepacia from a Patient with Cystic Fibrosis

    PubMed Central

    Miller, Ruth R.; Hird, Trevor J.; Tang, Patrick; Zlosnik, James E. A.

    2015-01-01

    Burkholderia cepacia complex bacteria are amongst the most feared of pathogens in cystic fibrosis (CF). The BCC comprises at least 20 distinct species that can cause chronic and unpredictable lung infections in CF. Historically the species B. cenocepacia has been the most prevalent in CF infections and has been associated in some centers with high rates of mortality. Modeling chronic infection by B. cenocepacia in the laboratory is challenging and no models exist which effectively recapitulate CF disease caused by BCC bacteria. Therefore our understanding of factors that contribute towards the morbidity and mortality caused by this organism is limited. In this study we used whole-genome sequencing to examine the evolution of 3 clonal clinical isolates of B. cenocepacia from a patient with cystic fibrosis. The first isolate was from the beginning of infection, and the second two almost 10 years later during the final year of the patients’ life. These isolates also demonstrated phenotypic heterogeneity, with the first isolate displaying the mucoid phenotype (conferred by the overproduction of exopolysaccharide), while one of the later two was nonmucoid. In addition we also sequenced a nonmucoid derivative of the initial mucoid isolate, acquired in the laboratory by antibiotic pressure. Examination of sequence data revealed that the two late stage isolates shared 20 variant nucleotides in common compared to the early isolate. However, despite their isolation within 10 months of one another, there was also considerable variation between the late stage isolates, including 42 single nucleotide variants and three deletions. Additionally, no sequence differences were identified between the initial mucoid isolate and its laboratory acquired nonmucoid derivative, however transcript analysis indicated at least partial down regulation of genes involved in exopolysaccharide production. Our study examines the progression of B. cenocepacia throughout chronic infection

  18. File concepts for parallel I/O

    NASA Technical Reports Server (NTRS)

    Crockett, Thomas W.

    1989-01-01

    The subject of input/output (I/O) was often neglected in the design of parallel computer systems, although for many problems I/O rates will limit the speedup attainable. The I/O problem is addressed by considering the role of files in parallel systems. The notion of parallel files is introduced. Parallel files provide for concurrent access by multiple processes, and utilize parallelism in the I/O system to improve performance. Parallel files can also be used conventionally by sequential programs. A set of standard parallel file organizations is proposed, organizations are suggested, using multiple storage devices. Problem areas are also identified and discussed.

  19. MRSA Causing Infections in Hospitals in Greater Metropolitan New York: Major Shift in the Dominant Clonal Type between 1996 and 2014

    PubMed Central

    Pardos de la Gandara, Maria; Curry, Marie; Berger, Judith; Burstein, David; Della-Latta, Phyllis; Kopetz, Virgina; Quale, John; Spitzer, Eric; Tan, Rexie; Urban, Carl; Wang, Guiqing; Whittier, Susan; de Lencastre, Herminia; Tomasz, Alexander

    2016-01-01

    A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)–also known as the “New York/Japan” clone—as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone–dominant in the 1996 survey–still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) and was associated with 84.5% of SSTIs compared to 5% caused by the USA100 clone. Our data indicate that by 2013/14, the USA300 clone replaced the New York/Japan clone as the most frequent cause of MRSA infections in hospitals in Metropolitan New York. In parallel with this shift in the clonal type of MRSA, there was also a striking change in the types of MRSA infections from 1996 to 2014. PMID:27272665

  20. Matpar: Parallel Extensions for MATLAB

    NASA Technical Reports Server (NTRS)

    Springer, P. L.

    1998-01-01

    Matpar is a set of client/server software that allows a MATLAB user to take advantage of a parallel computer for very large problems. The user can replace calls to certain built-in MATLAB functions with calls to Matpar functions.

  1. Parallel, Distributed Scripting with Python

    SciTech Connect

    Miller, P J

    2002-05-24

    Parallel computers used to be, for the most part, one-of-a-kind systems which were extremely difficult to program portably. With SMP architectures, the advent of the POSIX thread API and OpenMP gave developers ways to portably exploit on-the-box shared memory parallelism. Since these architectures didn't scale cost-effectively, distributed memory clusters were developed. The associated MPI message passing libraries gave these systems a portable paradigm too. Having programmers effectively use this paradigm is a somewhat different question. Distributed data has to be explicitly transported via the messaging system in order for it to be useful. In high level languages, the MPI library gives access to data distribution routines in C, C++, and FORTRAN. But we need more than that. Many reasonable and common tasks are best done in (or as extensions to) scripting languages. Consider sysadm tools such as password crackers, file purgers, etc ... These are simple to write in a scripting language such as Python (an open source, portable, and freely available interpreter). But these tasks beg to be done in parallel. Consider the a password checker that checks an encrypted password against a 25,000 word dictionary. This can take around 10 seconds in Python (6 seconds in C). It is trivial to parallelize if you can distribute the information and co-ordinate the work.

  2. Fast, Massively Parallel Data Processors

    NASA Technical Reports Server (NTRS)

    Heaton, Robert A.; Blevins, Donald W.; Davis, ED

    1994-01-01

    Proposed fast, massively parallel data processor contains 8x16 array of processing elements with efficient interconnection scheme and options for flexible local control. Processing elements communicate with each other on "X" interconnection grid with external memory via high-capacity input/output bus. This approach to conditional operation nearly doubles speed of various arithmetic operations.

  3. Optical Interferometric Parallel Data Processor

    NASA Technical Reports Server (NTRS)

    Breckinridge, J. B.

    1987-01-01

    Image data processed faster than in present electronic systems. Optical parallel-processing system effectively calculates two-dimensional Fourier transforms in time required by light to travel from plane 1 to plane 8. Coherence interferometer at plane 4 splits light into parts that form double image at plane 6 if projection screen placed there.

  4. Tutorial: Parallel Simulation on Supercomputers

    SciTech Connect

    Perumalla, Kalyan S

    2012-01-01

    This tutorial introduces typical hardware and software characteristics of extant and emerging supercomputing platforms, and presents issues and solutions in executing large-scale parallel discrete event simulation scenarios on such high performance computing systems. Covered topics include synchronization, model organization, example applications, and observed performance from illustrative large-scale runs.

  5. The physics of parallel machines

    NASA Technical Reports Server (NTRS)

    Chan, Tony F.

    1988-01-01

    The idea is considered that architectures for massively parallel computers must be designed to go beyond supporting a particular class of algorithms to supporting the underlying physical processes being modelled. Physical processes modelled by partial differential equations (PDEs) are discussed. Also discussed is the idea that an efficient architecture must go beyond nearest neighbor mesh interconnections and support global and hierarchical communications.

  6. Parallel distributed computing using Python

    NASA Astrophysics Data System (ADS)

    Dalcin, Lisandro D.; Paz, Rodrigo R.; Kler, Pablo A.; Cosimo, Alejandro

    2011-09-01

    This work presents two software components aimed to relieve the costs of accessing high-performance parallel computing resources within a Python programming environment: MPI for Python and PETSc for Python. MPI for Python is a general-purpose Python package that provides bindings for the Message Passing Interface (MPI) standard using any back-end MPI implementation. Its facilities allow parallel Python programs to easily exploit multiple processors using the message passing paradigm. PETSc for Python provides access to the Portable, Extensible Toolkit for Scientific Computation (PETSc) libraries. Its facilities allow sequential and parallel Python applications to exploit state of the art algorithms and data structures readily available in PETSc for the solution of large-scale problems in science and engineering. MPI for Python and PETSc for Python are fully integrated to PETSc-FEM, an MPI and PETSc based parallel, multiphysics, finite elements code developed at CIMEC laboratory. This software infrastructure supports research activities related to simulation of fluid flows with applications ranging from the design of microfluidic devices for biochemical analysis to modeling of large-scale stream/aquifer interactions.

  7. PALM: a Parallel Dynamic Coupler

    NASA Astrophysics Data System (ADS)

    Thevenin, A.; Morel, T.

    2008-12-01

    In order to efficiently represent complex systems, numerical modeling has to rely on many physical models at a time: an ocean model coupled with an atmospheric model is at the basis of climate modeling. The continuity of the solution is granted only if these models can constantly exchange information. PALM is a coupler allowing the concurrent execution and the intercommunication of programs not having been especially designed for that. With PALM, the dynamic coupling approach is introduced: a coupled component can be launched and can release computers' resources upon termination at any moment during the simulation. In order to exploit as much as possible computers' possibilities, the PALM coupler handles two levels of parallelism. The first level concerns the components themselves. While managing the resources, PALM allocates the number of processes which are necessary to any coupled component. These models can be parallel programs based on domain decomposition with MPI or applications multithreaded with OpenMP. The second level of parallelism is a task parallelism: one can define a coupling algorithm allowing two or more programs to be executed in parallel. PALM applications are implemented via a Graphical User Interface called PrePALM. In this GUI, the programmer initially defines the coupling algorithm then he describes the actual communications between the models. PALM offers a very high flexibility for testing different coupling techniques and for reaching the best load balance in a high performance computer. The transformation of computational independent code is almost straightforward. The other qualities of PALM are its easy set-up, its flexibility, its performances, the simple updates and evolutions of the coupled application and the many side services and functions that it offers.

  8. Research on B Cell Algorithm for Learning to Rank Method Based on Parallel Strategy

    PubMed Central

    Tian, Yuling; Zhang, Hongxian

    2016-01-01

    For the purposes of information retrieval, users must find highly relevant documents from within a system (and often a quite large one comprised of many individual documents) based on input query. Ranking the documents according to their relevance within the system to meet user needs is a challenging endeavor, and a hot research topic–there already exist several rank-learning methods based on machine learning techniques which can generate ranking functions automatically. This paper proposes a parallel B cell algorithm, RankBCA, for rank learning which utilizes a clonal selection mechanism based on biological immunity. The novel algorithm is compared with traditional rank-learning algorithms through experimentation and shown to outperform the others in respect to accuracy, learning time, and convergence rate; taken together, the experimental results show that the proposed algorithm indeed effectively and rapidly identifies optimal ranking functions. PMID:27487242

  9. Asexual reproduction does not produce clonal populations of the brooding coral Pocillopora damicornis on the Great Barrier Reef, Australia

    NASA Astrophysics Data System (ADS)

    Sherman, C. D. H.; Ayre, D. J.; Miller, K. J.

    2006-03-01

    We have investigated the relationship between genotypic diversity, the mode of production of brooded larvae and disturbance in a range of reef habitats, in order to resolve the disparity between the reproductive mode and population structure reported for the brooding coral Pocillopora damicornis. Within 14 sites across six habitats, the ratio of the observed ( G o) to the expected ( G e) genotypic diversity ranged from 69 to 100% of that expected for random mating. At three other sites in two habitats the G o /G e ranged from 35 to 53%. Two of these sites were recently bleached, suggesting that asexual recruitment may be favoured after disturbance. Nevertheless, our data suggest that brooded larvae, from each of five habitats surveyed, were asexually produced. While clonal recruitment may be important in disturbed habitats, the lack of clonality detected, both in this and earlier surveys of 40 other sites, implies that a disturbance is normally insufficient to explain this species’ continued investment in clonal reproduction.

  10. Clonal rearrangement for immunoglobulin and T-cell receptor genes in systemic Castleman's disease. Association with Epstein-Barr virus.

    PubMed Central

    Hanson, C. A.; Frizzera, G.; Patton, D. F.; Peterson, B. A.; McClain, K. L.; Gajl-Peczalska, K. J.; Kersey, J. H.

    1988-01-01

    Castleman's disease is a morphologically and clinically heterogeneous lymphoproliferative disorder. Both a localized benign variant and an aggressive form with systemic manifestations have been described. To investigate the differences between these variants of Castleman's disease, the authors analyzed lymph node DNA from 4 patients with the localized type and 4 with the systemic type of Castleman's disease for immunoglobulin and T-cell receptor gene rearrangements. The role of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was also studied by viral genomic DNA probes. They detected clonal rearrangements in 3 of the 4 patients with the systemic variant of Castleman's; no patients with localized disease had rearrangements. Copies of EBV genome were also detected in 2 of the 3 patients with clonal rearrangements. These results suggest that systemic Castleman's disease is a disorder distinct from the classical localized variant in that it may evolve into a clonal lymphoproliferation. Images Figure 1 PMID:2833104

  11. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia

    PubMed Central

    Oshima, Koichi; Khiabanian, Hossein; da Silva-Almeida, Ana C.; Tzoneva, Gannie; Abate, Francesco; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Carpenter, Zachary; Penson, Alex; Perez-Garcia, Arianne; Eckert, Cornelia; Nicolas, Concepción; Balbin, Milagros; Sulis, Maria Luisa; Kato, Motohiro; Koh, Katsuyoshi; Paganin, Maddalena; Basso, Giuseppe; Gastier-Foster, Julie M.; Devidas, Meenakshi; Loh, Mignon L.; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A.

    2016-01-01

    Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID:27655895

  12. ANGUSTIFOLIA3 signaling coordinates proliferation between clonally distinct cells in leaves.

    PubMed

    Kawade, Kensuke; Horiguchi, Gorou; Usami, Takeshi; Hirai, Masami Yokota; Tsukaya, Hirokazu

    2013-05-06

    Coordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells. However, we found here that in addition to mesophyll cells, epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells.

  13. Clonal diversity and clone formation in the parthenogenetic Caucasian rock Lizard Darevskia dahli [corrected].

    PubMed

    Vergun, Andrey A; Martirosyan, Irena A; Semyenova, Seraphima K; Omelchenko, Andrey V; Petrosyan, Varos G; Lazebny, Oleg E; Tokarskaya, Olga N; Korchagin, Vitaly I; Ryskov, Alexey P

    2014-01-01

    The all-female Caucasian rock lizard species Darevskia dahli and other parthenogenetic species of this genus reproduce normally via true parthenogenesis. Previously, the genetic diversity of this species was analyzed using allozymes, mitochondrial DNA, and DNA fingerprint markers. In the present study, variation at three microsatellite loci was studied in 111 specimens of D. dahli from five populations from Armenia, and new information regarding clonal diversity and clone formation in D. dahli was obtained that suggests a multiple hybridization origin. All individuals but one were heterozygous at the loci studied. Based on specific allele combinations, 11 genotypes were identified among the individuals studied. Individuals with the same genotypes formed distinct clonal lineages: one major clone was represented by 72 individuals, an intermediate clone was represented by 21 individuals, and nine other clones were rare and represented by one or several individuals. A new approach based on the detection and comparison of genotype-specific markers formed by combinations of parental-specific markers was developed and used to identify at least three hybridization founder events that resulted in the initial formation of one major and two rare clones. All other clones, including the intermediate and seven rare clones, probably arose through postformation microsatellite mutations of the major clone. This approach can be used to identify hybridization founder events and to study clone formation in other unisexual taxa.

  14. Genetic Structure in Dwarf Bamboo (Bashania fangiana) Clonal Populations with Different Genet Ages

    PubMed Central

    Ma, Qing-qing; Song, Hui-xing; Zhou, Shi-qiang; Yang, Wan-qin; Li, De-sheng; Chen, Jin-song

    2013-01-01

    Amplified fragment length polymorphism (AFLP) fingerprints were used to reveal genotypic diversity of dwarf bamboo (Bashania fangiana) clonal populations with two different genet ages (≤30 years versus >70 years) at Wolong National Natural Reserve, Sichuan province, China. We generated AFLP fingerprints for 96 leaf samples, collected at 30 m intervals in the two populations, using ten selective primer pairs. A total of 92 genotypes were identified from the both populations. The mean proportion of distinguishable genotypes (G/N) was 0.9583 (0.9375 to 0.9792) and Simpson's index of diversity (D) was 0.9982 (0.9973 to 0.9991). So, two B. fangiana populations were multiclonal and highly diverse. The largest single clone may occur over a distance of about 30 m. Our results demonstrated that the genotypic diversity and genet density of B. fangiana clonal population did not change significantly (47 versus 45) with genet aging and low partitioned genetic differentiation was between the two populations (Gst = 0.0571). The analysis of molecular variance consistently showed that a large proportion of the genetic variation (87.79%) existed among the individuals within populations, whereas only 12.21% were found among populations. In addition, the high level of genotypic diversity in the two populations implies that the further works were needed to investigate the reasons for the poor seed set in B. fangiana after flowering. PMID:24244360

  15. Reproductive strategies and isolation-by-demography in a marine clonal plant along an eutrophication gradient.

    PubMed

    Oliva, Silvia; Romero, Javier; Pérez, Marta; Manent, Pablo; Mascaró, Oriol; Serrão, Ester A; Coelho, Nelson; Alberto, Filipe

    2014-12-01

    Genetic diversity in clonal organisms includes two distinct components, (i) the diversity of genotypes or clones (i.e. genotypic richness) in a population and (ii) that of the alleles (i.e. allelic and gene diversity within populations, and differentiation between populations). We investigated how population differentiation and genotypic components are associated across a gradient of eutrophication in a clonal marine plant. To that end, we combined direct measurements of sexual allocation (i.e. flower and seed counts) and genotypic analyses, which are used as an estimator of effective sexual reproduction across multiple generations. Genetic differentiation across sites was also modelled according to a hypothesis here defined as isolation-by-demography, in which we use population-specific factors, genotypic richness and eutrophication that are hypothesized to affect the source-sink dynamics and thus influence the genetic differentiation between a pair of populations. Eutrophic populations exhibited lower genotypic richness, in agreement with lower direct measurements of sexual allocation and contemporaneous gene flow. Genetic differentiation, while not explained by distance, was best predicted by genotypic richness and habitat quality. A multiple regression model using these two predictors was considered the best model (R(2) = 0.43). In this study, the relationship between environment and effective sexual-asexual balance is not simply (linearly) predicted by direct measurements of sexual allocation. Our results indicate that population-specific factors and the isolation-by-demography model should be used more often to understand genetic differentiation.

  16. Cryptosporidium,Giardia, Cryptococcus, Pneumocystis genetic variability: cryptic biological species or clonal near-clades?

    PubMed

    Tibayrenc, Michel; Ayala, Francisco J

    2014-04-01

    An abundant literature dealing with the population genetics and taxonomy of Giardia duodenalis, Cryptosporidium spp., Pneumocystis spp., and Cryptococcus spp., pathogens of high medical and veterinary relevance, has been produced in recent years. We have analyzed these data in the light of new population genetic concepts dealing with predominant clonal evolution (PCE) recently proposed by us. In spite of the considerable phylogenetic diversity that exists among these pathogens, we have found striking similarities among them. The two main PCE features described by us, namely highly significant linkage disequilibrium and near-clading (stable phylogenetic clustering clouded by occasional recombination), are clearly observed in Cryptococcus and Giardia, and more limited indication of them is also present in Cryptosporidium and Pneumocystis. Moreover, in several cases, these features still obtain when the near-clades that subdivide the species are analyzed separately ("Russian doll pattern"). Lastly, several sets of data undermine the notion that certain microbes form clonal lineages simply owing to a lack of opportunity to outcross due to low transmission rates leading to lack of multiclonal infections ("starving sex hypothesis"). We propose that the divergent taxonomic and population genetic inferences advanced by various authors about these pathogens may not correspond to true evolutionary differences and could be, rather, the reflection of idiosyncratic practices among compartmentalized scientific communities. The PCE model provides an opportunity to revise the taxonomy and applied research dealing with these pathogens and others, such as viruses, bacteria, parasitic protozoa, and fungi.

  17. Simultaneous Mendelian and clonal genome transmission in a sexually reproducing, all-triploid vertebrate

    PubMed Central

    Stöck, Matthias; Ustinova, Jana; Betto-Colliard, Caroline; Schartl, Manfred; Moritz, Craig; Perrin, Nicolas

    2012-01-01

    Meiosis in triploids faces the seemingly insuperable difficulty of dividing an odd number of chromosome sets by two. Triploid vertebrates usually circumvent this problem through either asexuality or some forms of hybridogenesis, including meiotic hybridogenesis that involve a reproductive community of different ploidy levels and genome composition. Batura toads (Bufo baturae; 3n = 33 chromosomes), however, present an all-triploid sexual reproduction. This hybrid species has two genome copies carrying a nucleolus-organizing region (NOR+) on chromosome 6, and a third copy without it (NOR−). Males only produce haploid NOR+ sperm, while ova are diploid, containing one NOR+ and one NOR− set. Here, we conduct sibship analyses with co-dominant microsatellite markers so as (i) to confirm the purely clonal and maternal transmission of the NOR− set, and (ii) to demonstrate Mendelian segregation and recombination of the NOR+ sets in both sexes. This new reproductive mode in vertebrates (‘pre-equalizing hybrid meiosis’) offers an ideal opportunity to study the evolution of non-recombining genomes. Elucidating the mechanisms that allow simultaneous transmission of two genomes, one of Mendelian, the other of clonal inheritance, might shed light on the general processes that regulate meiosis in vertebrates. PMID:21993502

  18. Clonal CD8+ TCR-Vbeta expanded populations with effector memory phenotype in Churg Strauss syndrome.

    PubMed

    Guida, Giuseppe; Vallario, Antonella; Stella, Stefania; Boita, Monica; Circosta, Paola; Mariani, Sara; Prato, Giuseppina; Heffler, Enrico; Bergia, Roberta; Sottile, Antonino; Rolla, Giovanni; Cignetti, Alessandro

    2008-07-01

    Churg Strauss Syndrome (CSS) is a systemic vasculitis in which oligoclonal T cell expansions might be involved in the pathogenesis. Combined analysis of TCR-Vbeta expression profile by flow cytometry and of TCR gene rearrangement by heteroduplex PCR was used to detect and characterize T cell expansions in 8 CSS patients, 10 asthmatics and 42 healthy subjects. In all CSS patients one or two Vbeta families were expanded among CD8+ cells, with an effector memory phenotype apt to populate tissues and inflammatory sites. Heteroduplex PCR showed the presence of one or more clonal TCR rearrangements, which reveals monoclonal or oligoclonal T cells subpopulations. After purification with a Vbeta specific monoclonal antibody, each CD8+/Vbeta+ expanded family showed a single TCR rearrangement, clearly suggestive of monoclonality. All CD8+ expansions were detectable throughout the disease course. TCR-Vbeta expanded or deleted populations were not observed in asthmatic patients. Clonal CD8+/Vbeta+ T cell expansions might be useful as a disease marker.

  19. PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation[S

    PubMed Central

    Hallenborg, Philip; Petersen, Rasmus Koefoed; Feddersen, Søren; Sundekilde, Ulrik; Hansen, Jacob B.; Blagoev, Blagoy; Madsen, Lise; Kristiansen, Karsten

    2014-01-01

    Adipocyte differentiation is orchestrated by the ligand-activated nuclear receptor PPARγ. Endogenous ligands comprise oxidized derivatives of arachidonic acid and structurally similar PUFAs. Although expression of PPARγ peaks in mature adipocytes, ligands are produced primarily at the onset of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin-dependent kinase inhibitor p21, exhibit increased adipogenic potential. The antiadipogenic effect of p53 relied on its transcriptional activity and p21 expression but was circumvented by administration of an exogenous PPARγ agonist suggesting a linkage between cell cycling and PPARγ ligand production. Indeed, cell cycle inhibitory compounds decreased PPARγ ligand production in differentiating 3T3-L1 preadipocytes. Furthermore, these inhibitors abolished the release of arachidonic acid induced by the hormonal cocktail initiating adipogenesis. Collectively, our results suggest that murine fibroblasts require clonal expansion for PPARγ ligand production at the onset of adipocyte differentiation. PMID:25312885

  20. Intratumoral heterogeneity: Clonal cooperation in epithelial-to-mesenchymal transition and metastasis

    PubMed Central

    Neelakantan, Deepika; Drasin, David J; Ford, Heide L

    2015-01-01

    Although phenotypic intratumoral heterogeneity was first described many decades ago, the advent of next-generation sequencing has provided conclusive evidence that in addition to phenotypic diversity, significant genotypic diversity exists within tumors. Tumor heterogeneity likely arises both from clonal expansions, as well as from differentiation hierarchies existent in the tumor, such as that established by cancer stem cells (CSCs) and non-CSCs. These differentiation hierarchies may arise due to genetic mutations, epigenetic alterations, or microenvironmental influences. An additional differentiation hierarchy within epithelial tumors may arise when only a few tumor cells trans-differentiate into mesenchymal-like cells, a process known as epithelial-to-mesenchymal transition (EMT). Again, this process can be influenced by both genetic and non-genetic factors. In this review we discuss the evidence for clonal interaction and cooperation for tumor maintenance and progression, particularly with respect to EMT, and further address the far-reaching effects that tumor heterogeneity may have on cancer therapy. PMID:25482627

  1. Incomplete clonal deletion as prerequisite for tissue-specific minor antigen tolerization

    PubMed Central

    Mahr, Benedikt; Unger, Lukas; Hock, Karin; Schwarz, Christoph; Farkas, Andreas M.; Baranyi, Ulrike; Wrba, Fritz

    2016-01-01

    Central clonal deletion has been considered the critical factor responsible for the robust state of tolerance achieved by chimerism-based experimental protocols, but split-tolerance models and the clinical experience are calling this assumption into question. Although clone-size reduction through deletion has been shown to be universally required for achieving allotolerance, it remains undetermined whether it is sufficient by itself. Therapeutic Treg treatment induces chimerism and tolerance in a stringent murine BM transplantation model devoid of myelosuppressive recipient treatment. In contrast to irradiation chimeras, chronic rejection (CR) of skin and heart allografts in Treg chimeras was permanently prevented, even in the absence of complete clonal deletion of donor MHC-reactive T cells. We show that minor histocompatibility antigen mismatches account for CR in irradiation chimeras without global T cell depletion. Furthermore, we show that Treg therapy–induced tolerance prevents CR in a linked suppression–like fashion, which is maintained by active regulatory mechanisms involving recruitment of thymus-derived Tregs to the graft. These data suggest that highly efficient intrathymic and peripheral deletion of donor-reactive T cells for specificities expressed on hematopoietic cells preclude the expansion of donor-specific Tregs and, hence, do not allow for spreading of tolerance to minor specificities that are not expressed by donor BM. PMID:27699263

  2. Clonal and pathotypic analysis of archetypal Escherichia coli cystitis isolate NU14.

    PubMed

    Johnson, J R; Weissman, S J; Stell, A L; Trintchina, E; Dykhuizen, D E; Sokurenko, E V

    2001-12-15

    Escherichia coli NU14, a cystitis isolate used to study the pathogenesis of cystitis and to develop a FimH (type 1 fimbrial adhesin) vaccine, was assessed for extended virulence genotype, phylogenetic background, and FimH sequence and binding phenotype(s). NU14 exhibited the same virulence genotype and was derived from the same (meningitis- and cystitis-associated) subclone of E. coli O18:K1:H7 as the archetypal neonatal bacterial meningitis (NBM) isolate RS218. NU14 also displayed the same Ser62Ala FimH polymorphism as did NBM isolates RS218 and IHE3034-conferring both collagen binding and a distinct monomannose binding capability (which characterizes uropathogenic but not commensal E. coli and dramatically increases adherence to uroepithelial cells). These findings establish that strain NU14 exhibits numerous urovirulence-associated traits and derives from the single most prevalent clonal group in acute cystitis. They provide further evidence of clonal and pathotypic similarities between cystitis and NBM isolates of E. coli O18:K1:H7.

  3. Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia.

    PubMed

    Januszkiewicz, D A; Nowak, J S

    1994-09-01

    DNA-based PCR with various sets of primers for TCR gamma/delta, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3, V delta 2 to D delta 2, or D delta 3 to D delta 2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of V gamma I group, the most frequent gene usage concerns regions V gamma 2, V gamma 4, and psi V gamma 7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.

  4. Hospital clonal dissemination of Enterobacter aerogenes producing carbapenemase KPC-2 in a Chinese teaching hospital.

    PubMed

    Qin, Xiaohua; Yang, Yang; Hu, Fupin; Zhu, Demei

    2014-02-01

    Carbapenems are first-line agents for the treatment of serious nosocomial infections caused by multidrug-resistant Enterobacteriaceae. However, resistance to carbapenems has increased dramatically among Enterobacteriaceae in our hospital. In this study, we report clonal dissemination caused by carbapenem-resistant Enterobacter aerogenes (CREA). In 2011, CREA was identified from 12 patients admitted to the neurosurgical ward. All 12 clinical isolates were non-susceptible to cefotaxime, ceftazidime, cefoxitin, ertapenem, imipenem or meropenem. All isolates carried the gene encoding Klebsiella pneumoniae carbapenemase-2 (KPC-2), except for the isolate E4. However, a remarkably lower expression level of the porin OmpF was detected in the non-KPC-2-producing isolate E4 on SDS-PAGE compared with the carbapenem-susceptible isolate. Epidemiological and molecular investigations showed that a single E. aerogenes strain (PFGE type A), including seven KPC-2-producing clinical isolates, was primarily responsible for the first isolation and subsequent dissemination. In a case-control study, we identified risk factors for infection/colonization with CREA. Mechanical ventilation, the changing of sickbeds and previous use of broad-spectrum antibiotics were identified as potential risk factors. Our findings suggest that further studies should focus on judicious use of available antibiotics, implementation of active antibiotic resistance surveillance and strict implementation of infection-control measures to avoid the rapid spread or clonal dissemination caused by carbapenem-resistant Enterobacteriaceae in healthcare facilities.

  5. Clonal origins of cells in the pigmented retina of the zebrafish eye

    SciTech Connect

    Streisinger, G.; Coale, F.; Taggart, C.; Walker, C.; Grunwald, D.J.

    1989-01-01

    Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina.

  6. Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia

    PubMed Central

    Hirsch, Pierre; Zhang, Yanyan; Tang, Ruoping; Joulin, Virginie; Boutroux, Hélène; Pronier, Elodie; Moatti, Hannah; Flandrin, Pascale; Marzac, Christophe; Bories, Dominique; Fava, Fanny; Mokrani, Hayat; Betems, Aline; Lorre, Florence; Favier, Rémi; Féger, Frédéric; Mohty, Mohamad; Douay, Luc; Legrand, Ollivier; Bilhou-Nabera, Chrystèle; Louache, Fawzia; Delhommeau, François

    2016-01-01

    In acute myeloid leukaemia (AML) initiating pre-leukaemic lesions can be identified through three major hallmarks: their early occurrence in the clone, their persistence at relapse and their ability to initiate multilineage haematopoietic repopulation and leukaemia in vivo. Here we analyse the clonal composition of a series of AML through these characteristics. We find that not only DNMT3A mutations, but also TET2, ASXL1 mutations, core-binding factor and MLL translocations, as well as del(20q) mostly fulfil these criteria. When not eradicated by AML treatments, pre-leukaemic cells with these lesions can re-initiate the leukaemic process at various stages until relapse, with a time-dependent increase in clonal variegation. Based on the nature, order and association of lesions, we delineate recurrent genetic hierarchies of AML. Our data indicate that first lesions, variegation and treatment selection pressure govern the expansion and adaptive behaviour of the malignant clone, shaping AML in a time-dependent manner. PMID:27534895

  7. Genetic differentiation, recombination and clonal expansion in environmental populations of Cryptococcus gattii in India.

    PubMed

    Chowdhary, Anuradha; Hiremath, Sanjay S; Sun, Sheng; Kowshik, Tusharantak; Randhawa, Harbans S; Xu, Jianping

    2011-07-01

    Cryptococcus gattii is a ubiquitous eukaryotic pathogen capable of causing life-threatening infections in a wide variety of hosts, including both immunocompromised and immunocompetent humans. Since infections by C. gattii are predominantly obtained from environmental exposures, understanding environmental populations of this pathogen is critical, especially in countries like India with a large population and with environmental conditions conducive for the growth of C. gattii. In this study, we analysed 109 isolates of C. gattii obtained from hollows of nine tree species from eight geographic locations in India. Multilocus sequence typing was conducted for all isolates using nine gene fragments. All 109 isolates belonged to the VGI group and were mating type α. Population genetic analyses revealed limited evidence of recombination but unambiguous evidence for clonal reproduction and expansion. However, the observed clonal expansion has not obscured the significant genetic differentiation among populations from either different geographic areas or different host tree species. A positive correlation was observed between genetic distance and geographic distance. The results obtained here for environmental populations of C. gattii showed both similarities and differences with those of the closely related Cryptococcus neoformans var. grubii from similar locations and host tree species in India.

  8. Unusually Large Number of Mutations in Asexually Reproducing Clonal Planarian Dugesia japonica.

    PubMed

    Nishimura, Osamu; Hosoda, Kazutaka; Kawaguchi, Eri; Yazawa, Shigenobu; Hayashi, Tetsutaro; Inoue, Takeshi; Umesono, Yoshihiko; Agata, Kiyokazu

    2015-01-01

    We established a laboratory clonal strain of freshwater planarian (Dugesia japonica) that was derived from a single individual and that continued to undergo autotomous asexual reproduction for more than 20 years, and we performed large-scale genome sequencing and transcriptome analysis on it. Despite the fact that a completely clonal strain of the planarian was used, an unusually large number of mutations were detected. To enable quantitative genetic analysis of such a unique organism, we developed a new model called the Reference Gene Model, and used it to conduct large-scale transcriptome analysis. The results revealed large numbers of mutations not only outside but also inside gene-coding regions. Non-synonymous SNPs were detected in 74% of the genes for which valid ORFs were predicted. Interestingly, the high-mutation genes, such as metabolism- and defense-related genes, were correlated with genes that were previously identified as diverse genes among different planarian species. Although a large number of amino acid substitutions were apparently accumulated during asexual reproduction over this long period of time, the planarian maintained normal body-shape, behaviors, and physiological functions. The results of the present study reveal a unique aspect of asexual reproduction.

  9. A Novel Hybrid Clonal Selection Algorithm with Combinatorial Recombination and Modified Hypermutation Operators for Global Optimization

    PubMed Central

    Lin, Jingjing; Jing, Honglei

    2016-01-01

    Artificial immune system is one of the most recently introduced intelligence methods which was inspired by biological immune system. Most immune system inspired algorithms are based on the clonal selection principle, known as clonal selection algorithms (CSAs). When coping with complex optimization problems with the characteristics of multimodality, high dimension, rotation, and composition, the traditional CSAs often suffer from the premature convergence and unsatisfied accuracy. To address these concerning issues, a recombination operator inspired by the biological combinatorial recombination is proposed at first. The recombination operator could generate the promising candidate solution to enhance search ability of the CSA by fusing the information from random chosen parents. Furthermore, a modified hypermutation operator is introduced to construct more promising and efficient candidate solutions. A set of 16 common used benchmark functions are adopted to test the effectiveness and efficiency of the recombination and hypermutation operators. The comparisons with classic CSA, CSA with recombination operator (RCSA), and CSA with recombination and modified hypermutation operator (RHCSA) demonstrate that the proposed algorithm significantly improves the performance of classic CSA. Moreover, comparison with the state-of-the-art algorithms shows that the proposed algorithm is quite competitive. PMID:27698662

  10. Effects of clonal fragmentation on intraspecific competition of a stoloniferous floating plant.

    PubMed

    Wang, P; Xu, Y-S; Dong, B-C; Xue, W; Yu, F-H

    2014-11-01

    Disturbance is common and can fragment clones of plants. Clonal fragmentation may affect the density and growth of ramets so that it could alter intraspecific competition. To test this hypothesis, we grew one (low density), five (medium density) or nine (high density) parent ramets of the floating invasive plant Pistia stratiotes in buckets, and newly produced offspring ramets were either severed (with fragmentation) or remained connected to parent ramets (no fragmentation). Increasing density reduced biomass of the whole clone (i.e. parent ramet plus its offspring ramets), showing intense intraspecific competition. Fragmentation decreased biomass of offspring ramets, but increased biomass of parent ramets and the whole clone, suggesting significant resource translocation from parent to offspring ramets when clones were not fragmented. There was no interaction effect of density x fragmentation on biomass of the whole clone, and fragmentation did not affect competition intensity index. We conclude that clonal fragmentation does not alter intraspecific competition between clones of P. stratiotes, but increases biomass production of the whole clone. Thus, fragmentation may contribute to its interspecific competitive ability and invasiveness, and intentional fragmentation should not be recommended as a measure to stop the rapid growth of this invasive species.

  11. Evidence of the three main clonal Toxoplasma gondii lineages from wild mammalian carnivores in the UK.

    PubMed

    Burrells, A; Bartley, P M; Zimmer, I A; Roy, S; Kitchener, A C; Meredith, A; Wright, S E; Innes, E A; Katzer, F

    2013-12-01

    Toxoplasma gondii is a zoonotic pathogen defined by three main clonal lineages (types I, II, III), of which type II is most common in Europe. Very few data exist on the prevalence and genotypes of T. gondii in the UK. Wildlife can act as sentinel species for T. gondii genotypes present in the environment, which may subsequently be transmitted to livestock and humans. DNA was extracted from tissue samples of wild British carnivores, including 99 ferrets, 83 red foxes, 70 polecats, 65 mink, 64 badgers and 9 stoats. Parasite DNA was detected using a nested ITS1 PCR specific for T. gondii, PCR positive samples were subsequently genotyped using five PCR-RFLP markers. Toxoplasma gondii DNA was detected within all these mammal species and prevalence varied from 6·0 to 44·4% depending on the host. PCR-RFLP genotyping identified type II as the predominant lineage, but type III and type I alleles were also identified. No atypical or mixed genotypes were identified within these animals. This study demonstrates the presence of alleles for all three clonal lineages with potential for transmission to cats and livestock. This is the first DNA-based study of T. gondii prevalence and genotypes across a broad range of wild British carnivores.

  12. Complex Antigens Elicit Diverse Patterns of Clonal Selection in Germinal Centers

    PubMed Central

    Kuraoka, Masayuki; Schmidt, Aaron G.; Nojima, Takuya; Feng, Feng; Watanabe, Akiko; Kitamura, Daisuke; Harrison, Stephen C.; Kepler, Thomas B.; Kelsoe, Garnett

    2016-01-01

    SUMMARY Germinal center (GC) B cells evolve towards increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two complex antigens – Bacillus anthracis protective antigen and influenza hemagglutinin – in which B cells competed both intra- and interclonally for distinct epitopes. Preferred VH rearrangements among antigen-binding, naïve B cells were similarly abundant in early GCs but, unlike responses to haptens, clonal diversity increased in GC B cells as early “winners” were replaced by rarer, high-affinity clones. Despite affinity maturation, inter- and intraclonal avidities varied greatly, and half of GC B cells did not bind the immunogen but nonetheless exhibited biased VH use, V(D)J mutation, and clonal expansion comparable to antigen-binding cells. GC reactions to complex antigens permit a range of specificities and affinities, with potential advantages for broad protection. PMID:26948373

  13. Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors.

    PubMed

    Kepler, Thomas B

    2013-01-01

    One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the eliciting antigen. Advances in technology on several fronts have made it possible to clone large numbers of heavy-chain light-chain pairs from individual B cells and thereby identify whole sets of clonally related antibodies. These collections could provide the information necessary to reconstruct their own history - the sequence of changes introduced into the lineage during the development of the clone - and to study affinity maturation in detail. But the success of such a program depends entirely on accurately inferring the founding ancestor and the other unobserved intermediates. Given a set of clonally related immunoglobulin V-region genes, the method described here allows one to compute the posterior distribution over their possible ancestors, thereby giving a thorough accounting of the uncertainty inherent in the reconstruction. I demonstrate the application of this method on heavy-chain and light-chain clones, assess the reliability of the inference, and discuss the sources of uncertainty.

  14. How old are you? Genet age estimates in a clonal animal.

    PubMed

    Devlin-Durante, M K; Miller, M W; Precht, W F; Baums, I B

    2016-11-01

    Foundation species such as redwoods, seagrasses and corals are often long-lived and clonal. Genets may consist of hundreds of members (ramets) and originated hundreds to thousands of years ago. As climate change and other stressors exert selection pressure on species, the demography of populations changes. Yet, because size does not indicate age in clonal organisms, demographic models are missing data necessary to predict the resilience of many foundation species. Here, we correlate somatic mutations with genet age of corals and provide the first, preliminary estimates of genet age in a colonial animal. We observed somatic mutations at five microsatellite loci in rangewide samples of the endangered coral, Acropora palmata (n = 3352). Colonies harboured 342 unique mutations in 147 genets. Genet age ranged from 30 to 838 years assuming a mutation rate of 1.195(-04) per locus per year based on colony growth rates and 236 to 6500 years assuming a mutation rate of 1.542(-05) per locus per year based on sea level changes to habitat availability. Long-lived A. palmata genets imply a large capacity to tolerate past environmental change, and yet recent mass mortality events in A. palmata suggest that capacity is now being frequently exceeded.

  15. Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization

    PubMed Central

    Christ, Daniel

    2016-01-01

    Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and >43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses. PMID:27298445

  16. Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.

    PubMed

    Soh, Boon-Seng; Ng, Shi-Yan; Wu, Hao; Buac, Kristina; Park, Joo-Hye C; Lian, Xiaojun; Xu, Jiejia; Foo, Kylie S; Felldin, Ulrika; He, Xiaobing; Nichane, Massimo; Yang, Henry; Bu, Lei; Li, Ronald A; Lim, Bing; Chien, Kenneth R

    2016-03-08

    Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human-mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1(+) vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo.

  17. Genetically diverse long-lived clonal lineages of Phytophthora capsici from pepper in Gansu, China.

    PubMed

    Hu, Jian; Pang, Zhili; Bi, Yang; Shao, Jingpeng; Diao, Yongzhao; Guo, Jianguo; Liu, Yonggang; Lv, Heping; Lamour, Kurt; Liu, Xili

    2013-09-01

    Phytophthora capsici causes significant loss to pepper production in China, and our objective was to investigate the population structure in Gansu province. Between 2007 and 2011, 279 isolates were collected from pepper at 24 locations. Isolates (or subsets) were assessed for simple sequence repeat (SSR) genotype, metalaxyl resistance, mating type, and physiological race using cultivars from the World Vegetable Center (AVRDC) and New Mexico recombinant inbred lines (NMRILs). The A1 and A2 mating types were recovered from nine locations and metalaxyl-resistant isolates from three locations. A total of 104 isolates tested on the AVRDC panel resolved five physiological races. None of 42 isolates tested on the NMRIL panel caused visible infection. SSR genotyping of 127 isolates revealed 59 unique genotypes, with 42 present as singletons and 17 having 2 to 13 isolates. Isolates with identical genotypes were recovered from multiple sites across multiple years and, in many cases, had different race types or metalaxyl sensitivities. Isolates clustered into three groups with each group having almost exclusively the A1 or A2 mating type. Overall it appears long-lived genetically diverse clonal lineages are dispersed across Gansu, outcrossing is rare, and functionally important variation exists within a clonal framework.

  18. Mitochondria: Biogenesis and mitophagy balance in segregation and clonal expansion of mitochondrial DNA mutations.

    PubMed

    Carelli, Valerio; Maresca, Alessandra; Caporali, Leonardo; Trifunov, Selena; Zanna, Claudia; Rugolo, Michela

    2015-06-01

    Mitochondria are cytoplasmic organelles containing their own multi-copy genome. They are organized in a highly dynamic network, resulting from balance between fission and fusion, which maintains homeostasis of mitochondrial mass through mitochondrial biogenesis and mitophagy. Mitochondrial DNA (mtDNA) mutates much faster than nuclear DNA. In particular, mtDNA point mutations and deletions may occur somatically and accumulate with aging, coexisting with the wild type, a condition known as heteroplasmy. Under specific circumstances, clonal expansion of mutant mtDNA may occur within single cells, causing a wide range of severe human diseases when mutant overcomes wild type. Furthermore, mtDNA deletions accumulate and clonally expand as a consequence of deleterious mutations in nuclear genes involved in mtDNA replication and maintenance, as well as in mitochondrial fusion genes (mitofusin-2 and OPA1), possibly implicating mtDNA nucleoids segregation. We here discuss how the intricacies of mitochondrial homeostasis impinge on the intracellular propagation of mutant mtDNA. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies.

  19. Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors

    PubMed Central

    Hafner, Christian; Toll, Agustí; Fernández-Casado, Alejandro; Earl, Julie; Marqués, Miriam; Acquadro, Francesco; Méndez-Pertuz, Marinela; Urioste, Miguel; Malats, Núria; Burns, Julie E.; Knowles, Margaret A.; Cigudosa, Juan C.; Hartmann, Arndt; Vogt, Thomas; Landthaler, Michael; Pujol, Ramón M.; Real, Francisco X.

    2010-01-01

    Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin. PMID:21078999

  20. Clonal relatedness of Salmonella isolates associated with invasive infections in captive and wild-caught rattlesnakes.

    PubMed

    Bemis, David A; Grupka, Lisa M; Liamthong, Sumalee; Folland, Douglas W; Sykes, John M; Ramsay, Edward C

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