6,910 research outputs found

    Spontaneous ATM gene reversion in A-T iPSC to produce an isogenic cell line

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    A spontaneously reverted iPSC line was identified from an A-T subject with heterozygous ATM truncation mutations. The reverted iPSC line expressed ATM protein and was capable of radiation-induced phosphorylation of CHK2 and H2A.X. Genome-wide SNP analysis confirmed a match to source T-cells and also to a distinct, non-reverted iPSC line from the same subject. Rearranged T-cell receptor sequences predict that the iPSC culture originated as several independently reprogrammed cells that resolved into a single major clone, suggesting that gene correction likely occurred early in the reprogramming process. Gene expression analysis comparing ATM-/- iPSC lines to unrelated ATM+/- cells identifies a large number of differences but comparing only the isogenic pair of A-T iPSC lines reveals that the primary pathway affected by loss of ATM is a diminished expression of p53-related mRNAs. Gene reversion in culture, while likely a rare event, provided a novel, reverted cell line for studying ATM function.Peer reviewe

    The construction of Karen Karnak: The multi-author-function

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    This thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author

    ExoMol line lists - III. An improved hot rotation-vibration line list for HCN and HNC

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    A revised rotation-vibration line list for the combined hydrogen cyanide (HCN)/hydrogen isocyanide (HNC) system is presented. The line list uses ab initio transition intensities calculated previously and extensive data sets of recently measured experimental energy levels. The resulting line list has significantly more accurate wavelengths than previous ones for these systems. An improved value for the separation between HCN and HNC is adopted, leading to an approximately 25 per cent lower predicted thermal population of HNC as a function of temperature in the key 2000 to 3000 K region. Temperature-dependent partition functions and equilibrium constants are presented. The line lists are validated by comparison with laboratory spectra and are presented in full as supplementary data to the article and at www.exomol.com

    Modelling the magnetic activity and filtering radial velocity curves of young Suns : the weak-line T Tauri star LkCa 4

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    SGG acknowledges support from the Science & Technology Facilities Council (STFC) via an Ernest Rutherford Fellowship [ST/J003255/1]. SHPA acknowledges financial support from CNPq, CAPES and Fapemig.We report results of a spectropolarimetric and photometric monitoring of the weak-line T Tauri star LkCa 4 within the Magnetic Topologies of Young Stars and the Survival of close-in giant Exoplanets (MaTYSSE) programme, involving ESPaDOnS at the Canada–France–Hawaii Telescope. Despite an age of only 2 Myr and a similarity with prototypical classical T Tauri stars, LkCa 4 shows no evidence for accretion and probes an interesting transition stage for star and planet formation. Large profile distortions and Zeeman signatures are detected in the unpolarized and circularly polarized lines of LkCa 4 using Least-Squares Deconvolution (LSD), indicating the presence of brightness inhomogeneities and magnetic fields at the surface of LkCa 4. Using tomographic imaging, we reconstruct brightness and magnetic maps of LkCa 4 from sets of unpolarized and circularly polarized LSD profiles. The large-scale field is strong and mainly axisymmetric, featuring a ≃2 kG poloidal component and a ≃1 kG toroidal component encircling the star at equatorial latitudes – the latter making LkCa 4 markedly different from classical T Tauri stars of similar mass and age. The brightness map includes a dark spot overlapping the magnetic pole and a bright region at mid-latitudes – providing a good match to the contemporaneous photometry. We also find that differential rotation at the surface of LkCa 4 is small, typically ≃5.5 times weaker than that of the Sun, and compatible with solid-body rotation. Using our tomographic modelling, we are able to filter out the activity jitter in the radial velocity curve of LkCa 4 (of full amplitude 4.3 km s−1) down to an rms precision of 0.055 km s−1. Looking for hot Jupiters around young Sun-like stars thus appears feasible, even though we find no evidence for such planets around LkCa 4.Peer reviewe

    Line transect sampling of primates : can animal-to-observer distance methods work?

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    An erratum to this article can be found at http://dx.doi.org/10.1007/s10764-010-9469-4Line transect sampling is widely used for estimating abundance of primate populations. Animal-to-observer distances (AODs) are commonly used in analysis, in preference to perpendicular distances from the line. This is in marked contrast with standard practice for other applications of line transect sampling. We formalize the mathematical shortcomings of approaches based on AODs, and show that they are likely to give strongly biased estimates of density. We review papers that claim good performance for the method, and explore this performance through simulations. These confirm strong bias in estimates of density using AODs. We conclude that AOD methods are conceptually flawed, and that they cannot in general provide valid estimates of density.Peer reviewe

    Tagging of Biomedical Articles on CiteULike: A Comparison of User, Author and Professional Indexing

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    This paper examines the context of online indexing from the viewpoint of three different groups: users, authors, and professional indexers. User tags, author keywords and descriptors were collected from academic journal articles, which were both indexed in Pubmed and tagged on CiteULike, and analysed. Descriptive statistics, informetric measures, and thesaural term comparison shows that there are important differences in the use of keywords between the three groups in addition to similarities which can be used to enhance support for search and browse. While tags and author keywords were found that matched descriptors exactly, other terms which did not match but provided important expansion to the indexing lexicon were found. These additional terms could be used to enhance support for searching and browsing in article databases as well as to provide invaluable data for entry vocabulary and emergent terminology for regular updates to indexing systems. Additionally, the study suggests that tags support organisation by association to task, projects and subject while making important connections to traditional systems which classify into subject categories

    How the dispersion of a droplet cloud depends on its initial size

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    A cloud of droplets evolves under the influence of strong turbulence. The droplets are made from a phosphorescent fluid. From this cloud we select at t = 0 a narrow line by exciting the droplets with a UV laser, which causes them to glow for a few milliseconds. The dispersion of this line is followed in time using a fast intensified camera. A large range of droplet sizes (Stokes number St) was measured. It appears that lines with St \approx 1 disperse faster than a line of fluid tracers. Lines of droplets which are narrowest initially, spread fastest

    Magnetic activity and hot Jupiters of young Suns : the weak-line T Tauri stars V819 Tau and V830 Tau

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    SGG acknowledges support from the Science & Technology Facilities Council (STFC) via an Ernest Rutherford Fellowship [ST/J003255/1]. SHPA acknowledges financial support from CNPq, CAPES and Fapemig. AAV acknowledges support from the Swiss National Science Foundation (SNSF) via the allocation of an Ambizione Followship. Date of Acceptance: 06/08/2015We report results of a spectropolarimetric and photometric monitoring of the weak-line T Tauri stars (wTTSs) V819 Tau and V830 Tau within the MaTYSSE (Magnetic Topologies of Young Stars and the Survival of close-ingiant Exoplanets) programme, involving the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. At ≃3 Myr, both stars dissipated their discs recently and are interesting objects for probing star and planet formation. Profile distortions and Zeeman signatures are detected in the unpolarized and circularly polarized lines, whose rotational modulation we modelled using tomographic imaging, yielding brightness and magnetic maps for both stars. We find that the large-scale magnetic fields of V819 Tau and V830 Tau are mostly poloidal and can be approximated at large radii by 350-400 G dipoles tilted at≃30° to the rotation axis. They are significantly weaker than the field of GQ Lup, an accreting classical T Tauri star (cTTS) with similar mass and age which can be used to compare the magnetic properties of wTTSs and cTTSs. The reconstructed brightness maps of both stars include cool spots and warm plages. Surface differential rotation is small, typically ≃4.4 times smaller than on the Sun, in agreement with previous results on wTTSs. Using our Doppler images to model the activity jitter and filter it out from the radial velocity(RV) curves, we obtain RV residuals with dispersions of 0.033 and 0.104km s-1 for V819 Tau and V830 Tau, respectively. RV residuals suggest that a hot Jupiter may be orbiting V830 Tau, though additional data are needed to confirm this preliminary result. We find no evidence for close-in giant planet around V819 Tau.Peer reviewe

    DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

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    The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire

    Uma aplicação da transformada wavelet à verificação on-line da assinaturas manuscritas

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    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Ciência da Computação.Neste trabalho foi implementado um método direto que utiliza a transformada wavelet como o principal recurso para a verificação on-line de assinaturas manuscritas. As assinaturas, obtidas na forma de curvas x(t) e y(t) com o auxílio de uma prancheta digitalizadora, passam por uma etapa de pré-processamento e em seguida são submetidas a uma transformada wavelet. A partir destas funções transformadas, são obtidos números que caracterizam de maneira única cada assinatura. Em seguida, com base nestes números, são estabelecidas medidas de dissimilaridade (distância) entre cada assinatura a ser testada e uma assinatura padrão, previamente escolhida de uma amostra de dez assinaturas fornecidas pelo usuário durante um processo de cadastramento. Assume-se que toda nova assinatura deverá produzir distâncias até a padrão que estejam dentro de uma faixa aceitável em torno de médias verificadas no cadastramento. A determinação destas distâncias é efetuada de maneira não-linear, com o auxílio de uma técnica típica de reconhecimento de sons conhecida como "Dynamic Time Warping" (DTW). Esta técnica permite uma compensação em virtude de variações naturais no ritmo de escrita de cada pessoa a cada nova assinatura. Para recuperar a informação relativa à velocidade, perdida pela uniformização imposta pelo pré-processamento, é utilizada ainda uma outra medida de distância, calculada a partir do desvio das funções de warping para as diagonais correspondentes. A fim de justificar a inclusão da transformada wavelet, foi implementado um segundo sistema de verificação, seguindo uma abordagem em que as funções x(t) e y(t) são diretamente confrontadas com a assinatura padrão. Neste caso, as características são as próprias coordenadas dos pixels que descrevem cada assinatura e as medidas de dissimilaridade passam a ser simplesmente as normas das distâncias entre as curvas, cuja correspondência entre pontos também é determinada com o auxílio do DTW. A partir dos testes desenvolvidos, foram obtidas taxas de erro aceitáveis para este tipo de biometria nos dois sistemas implementados. O bom desempenho do caso em que as wavelets não foram incluídas, no entanto, sugere que, em ambos os sistemas, o principal mecanismo de verificação é a comparação não-linear entre parâmetros efetuada pelo DTW
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