36 research outputs found

    Developing linguistic research tools for virtual lexicographic laboratory of the spanish language explanatory dictionary

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    The present article is devoted to the problems of creating linguistic tools for the virtual lexicographic laboratory of Spanish explanatory dictionary (DLE 23). The goal of the research is to consider some issues related to the development of linguistic tools for the virtual lexicographic laboratory. To achieve this goal the dictionary was analyzed to define the peculiarities of linguistic facts representation, its structure and metalanguage. On the basis of the dictionary analysis and the theory of lexicographic systems the formal model of DLE 23 was developed and its main components, including their relationships, were determined to ensure their availability via linguistic tools for accessing linguistic information. The range of research activities to be performed by using the linguistic tools was outlined

    Developing linguistic research tools for virtual lexicographic laboratory of the spanish language explanatory dictionary

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    The present article is devoted to the problems of creating linguistic tools for the virtual lexicographic laboratory of Spanish explanatory dictionary (DLE 23). The goal of the research is to consider some issues related to the development of linguistic tools for the virtual lexicographic laboratory. To achieve this goal the dictionary was analyzed to define the peculiarities of linguistic facts representation, its structure and metalanguage. On the basis of the dictionary analysis and the theory of lexicographic systems the formal model of DLE 23 was developed and its main components, including their relationships, were determined to ensure their availability via linguistic tools for accessing linguistic information. The range of research activities to be performed by using the linguistic tools was outlined

    Nonhomologous end joining of complex DNA double-strand breaks with proximal thymine glycol and interplay with base excision repair

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    DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol at the first (Tg1), second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3' terminus, was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate base was a major barrier to end joining (>10-fold reduction in ligated products) and an absolute barrier when present at both ends. Dideoxy trapping of base excision repair intermediates indicated that Tg was excised from Tg1, Tg2 and Tg3 largely if not exclusively after DSB ligation. However, Tg was rapidly excised from the Tg5 substrate, resulting in a reduced level of DSB ligation, as well as slow concomitant resection of the opposite strand. Ligase reactions containing only purified Ku, XRCC4, ligase IV and XLF showed that ligation of Tg3 and Tg5 was efficient and only partially XLF-dependent, whereas ligation of Tg1 and Tg2 was inefficient and only detectable in the presence of XLF. Overall, the results suggest that promoting ligation of DSBs with proximal base damage may be an important function of XLF, but that Tg can still be a major impediment to repair, being relatively resistant to both trimming and ligation. Moreover, it appears that base excision repair of Tg can sometimes interfere with repair of DSBs that would otherwise be readily rejoined

    Trimming of damaged 3′ overhangs of DNA double-strand breaks by the Metnase and Artemis endonucleases

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    Both Metnase and Artemis possess endonuclease activities that trim 3′ overhangs of duplex DNA. To assess the potential of these enzymes for facilitating resolution of damaged ends during double-strand break rejoining, substrates bearing a variety of normal and structurally modified 3′ overhangs were constructed, and treated either with Metnase or with Artemis plus DNA-dependent protein kinase (DNA-PK). Unlike Artemis, which trims long overhangs to 4–5 bases, cleavage by Metnase was more evenly distributed over the length of the overhang, but with significant sequence dependence. In many substrates, Metnase also induced marked cleavage in the double-stranded region within a few bases of the overhang. Like Artemis, Metnase efficiently trimmed overhangs terminated in 3′-phosphoglycolates (PGs), and in some cases the presence of 3′-PG stimulated cleavage and altered its specificity. The nonplanar base thymine glycol in a 3′ overhang severely inhibited cleavage by Metnase in the vicinity of the modified base, while Artemis was less affected. Nevertheless, thymine glycol moieties could be removed by Metnase- or Artemis-mediated cleavage at sites farther from the terminus than the lesion itself. In in vitro end-joining systems based on human cell extracts, addition of Artemis, but not Metnase, effected robust trimming of an unligatable 3′-PG overhang, resulting in a dramatic stimulation of ligase IV- and XLF-dependent end joining. Thus, while both Metnase and Artemis are biochemically capable of resolving a variety of damaged DNA ends for the repair of complex double-strand breaks, Artemis appears to act more efficiently in the context of other nonhomologous end joining proteins

    Tyrosyl-DNA phosphodiesterase and the repair of 3′-phosphoglycolate-terminated DNA double-strand breaks

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    Although tyrosyl-DNA phosphodiesterase (TDP1) is capable of removing blocked 3′ termini from DNA double-strand break ends, it is uncertain whether this activity plays a role in double-strand break repair. To address this question, affinity-tagged TDP1 was overexpressed in human cells and purified, and its interactions with end joining proteins were assessed. Ku and DNA-PKcs inhibited TDP1-mediated processing of 3′-phosphoglycolate double-strand break termini, and in the absence of ATP, ends sequestered by Ku plus DNA-PKcs were completely refractory to TDP1. Addition of ATP restored TDP1-mediated end processing, presumably due to DNA-PK-catalyzed phosphorylation. Mutations in the 2609–2647 Ser/Thr phosphorylation cluster of DNA-PKcs only modestly affected such processing, suggesting that phosphorylation at other sites was important for rendering DNA ends accessible to TDP1. In human nuclear extracts, about 30% of PG termini were removed within a few hours despite very high concentrations of Ku and DNA-PKcs. Most such removal was blocked by the DNA-PK inhibitor KU-57788, but ~5% of PG termini were removed in the first few minutes of incubation even in extracts preincubated with inhibitor. The results suggest that despite an apparent lack of specific recruitment of TDP1 by DNA-PK, TDP1 can gain access to and can process blocked 3′ termini of double-strand breaks before ends are fully sequestered by DNA-PK, as well as at a later stage after DNA-PK autophosphorylation. Following cell treatment with calicheamicin, which specifically induces double-strand breaks with protruding 3′-PG termini, TDP1-mutant SCAN1 (spinocerebellar ataxia with axonal neuropathy) cells exhibited a much higher incidence of dicentric chromosomes, as well as higher incidence of chromosome breaks and micronuclei, than normal cells. This chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3′-PG double-strand breaks in vivo

    Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks

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    In mammalian cells, the main pathway for DNA double-strand breaks (DSBs) repair is classical non-homologous end joining (C-NHEJ). An alternative or back-up NHEJ (B-NHEJ) pathway has emerged which operates preferentially under C-NHEJ defective conditions. Although B-NHEJ appears particularly relevant to genomic instability associated with cancer, its components and regulation are still largely unknown. To get insights into this pathway, we have knocked-down Ku, the main contributor to C-NHEJ. Thus, models of human cell lines have been engineered in which the expression of Ku70/80 heterodimer can be significantly lowered by the conditional induction of a shRNA against Ku70. On Ku reduction in cells, resulting NHEJ competent protein extracts showed a shift from C- to B-NHEJ that could be reversed by addition of purified Ku protein. Using a cellular fractionation protocol after treatment with a strong DSBs inducer followed by western blotting or immunostaining, we established that, among C-NHEJ factors, Ku is the main counteracting factor against mobilization of PARP1 and the MRN complex to damaged chromatin. In addition, Ku limits PAR synthesis and single-stranded DNA production in response to DSBs. These data support the involvement of PARP1 and the MRN proteins in the B-NHEJ route for the repair of DNA DSBs

    Театралізація навчального процесу як елемент формування ключових компетенцій міжкультурної комунікації серед студентів, для яких англійська є іноземною

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    The article distinguishes the theatricalization of the educational process as an effective and to a certain degree innovative way of forming ESL students’ key competences. The authors of the article give the overview of the history of development of the concept “theatricalization”, its stages of implementing in teaching foreign languages and fundamental principles which it is based on and its niche in modern teaching methodology. The article mainly focuses on the experience of work at Business Foreign Languages and Translation Department of NTU “KhPI” (Ukraine) where dramatized performance is used both during extra-curriculum activities and class work. In the article there are also given and analyzed special examples of tasks which are assigned to ESL students within class work hours. On the whole, the authors regard as the most effective such kinds of class work dramatized performance as group work presented in the form of simulation of the business negotiations or discussion, acting in pairs within given imaginary situation, mono acting from the point of view of one of the characters, dramatized reciting of poems in the form of the video recording, staging pieces of classic literature and games for acting.У статті виділено театралізацію навчального процесу як ефективний і до певної міри інноваційний спосіб формування ключових компетенцій міжкультурної комунікації серед студентів, для яких англійська є іноземною. Автори статті дають огляд історії розвитку поняття "театралізація", етапи його впровадження у викладання іноземних мов та основоположні принципи, на яких вона базується, та її нішу в сучасній методиці викладання мов. Основна увага приділяється досвіду роботи на кафедрі ділової іноземної мови та перекладу НТУ "ХПІ", де театралізована вистава використовується під час аудиторних занять. У статті також наведені та проаналізовані приклади завдань для розвитку міжкультурної комунікації через театралізацію елементів освітнього процесу

    Multimedia in developing communicative competence among ESL students: cultural aspect

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    This article presents the results of the use of multimedia tools in the development of communicative competencies in terms of enhancing the cultural aspect in the process of teaching English to students who study it as a foreign language. Special attention is paid to the consideration of specific examples of the use of multimedia by teachers of the department of business foreign language and translation of the National Technical University "Kharkiv Polytechnic Institute".Стаття присвячена застосуванню мультимедійних технологій в процесі розвитку комунікативної компетентності серед студентів, які вивчають англійську мову як іноземну, з точки зору культурного аспекту. Автори статті розглядають історичні передумови виникнення такого поняття як мультимедія, аналізують етапи його розвитку, виділяють місце в сучасній педагогіці, а також відзначають його значення у сучасній методології навчання та викладання іноземної мови
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