232 research outputs found

    The development of professional social work values and ethics in the workplace: a critical incident analysis from the students' perspective

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    This thesis explores Greek social work students’ perceptions of the development of their professional values and ethics in the workplace during their professional practice placement. To accomplish its goals, the thesis includes a literature review and employs a qualitative exploratory research design with descriptive elements positioned within the constructivist paradigm. This research design allows the researcher to explore and describe a topic - social work values and ethics - that is generally under-researched in the existing literature, as well as being complex in nature and difficult to study. Data were collected using the critical incident technique (CIT). This method took the form of a written questionnaire (the CIT questionnaire) completed by 32 students between 11th and 25th October, 2010. The data were inductively analysed using both qualitative and quantitative approaches. SPSS and SPAD software packages were also used to analyse the numerical and textual data respectively. The study findings underline the vital role of the workplace as a social space for students to learn and develop their professional social work values and ethics. They also highlight the complexity of implementing social work values and ethics in the different workplace environments that students, as trainees, are placed for their professional practice due to their situation-specific nature. Further, the study reveals a number of factors that, from the students’ point of view, are important in applying and upholding professional ethical standards in social work practice. These factors are associated with: a) the need to practice social work values and ethics in the workplace on a daily basis in order to keep them alive and active; b) the students’ own contribution to upholding ethical standards; c) the role practice instructors/supervisors play in the transmission of social work values to students during their placements; d) the importance of ethical collaboration inside and outside the workplace to achieve the best practices for clients; e) the client’s behaviour as a determinant of the ethical practice of social workers in the workplace; and f) the importance of the ethics of management (including the political affiliation of the heads of organisations) in creating and sustaining an ethical work/learning environment. The study suggests that all the factors mentioned above-to a greater or lesser degree- should be considered important elements to take into account in the planning and development of values-based social work education programmes. Special attention should be paid to workplace conditions that can hinder or support the development of values-based social work practice. As the study clearly shows, daily ethical practice in social work, students as individuals, the role of practice instructors, ethical workplace collaboration, client behaviour, and the ethics of management are crucial components for building upon the ethical skills taught in the classroom and developing ethically informed professional identities in real-life workplace situations. The thesis concludes that the critical incidents experienced by students are a valuable source of knowledge and understanding of the development of social work values and ethics in professional practice. In this study, indeed, students gained valuable insights into their ethics development process in practice contexts, from both positive and negative critical incidents alike

    Dissection of a complex transcriptional response using genome-wide transcriptional modelling

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    Modern genomics technologies generate huge data sets creating a demand for systems level, experimentally verified, analysis techniques. We examined the transcriptional response to DNA damage in a human T cell line (MOLT4) using microarrays. By measuring both mRNA accumulation and degradation over a short time course, we were able to construct a mechanistic model of the transcriptional response. The model predicted three dominant transcriptional activity profiles—an early response controlled by NFκB and c-Jun, a delayed response controlled by p53, and a late response related to cell cycle re-entry. The method also identified, with defined confidence limits, the transcriptional targets associated with each activity. Experimental inhibition of NFκB, c-Jun and p53 confirmed that target predictions were accurate. Model predictions directly explained 70% of the 200 most significantly upregulated genes in the DNA-damage response. Genome-wide transcriptional modelling (GWTM) requires no prior knowledge of either transcription factors or their targets. GWTM is an economical and effective method for identifying the main transcriptional activators in a complex response and confidently predicting their targets

    Evaluation of ground information with respect to EPB tunnelling for the Thessaloniki metro, Greece

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    Ο Μητροπολιτικός σιδηρόδρομος της Θεσσαλονίκης αποτελείται από δύο παράλληλες σήραγγες διαμέτρου ~6 m και μήκους ~8 km η κάθε μία και περιλαμβάνει 13 σταθμούς. Η γεωλογία του πολεοδομικού συγκροτήματος της Θεσσαλονίκης χαρακτηρίζεται από την παρουσία νεογενών και τεταρτογενών αποθέσεων. Ο κύριος σχηματισμός της περιοχής του έργου είναι μία σειρά πολύ στιφρών έως σκληρών ερυθρών αργίλων ανωμειοκαινικής-πλειοκαινικής ηλικίας. Σχηματισμοί του Τεταρτογενούς που έχουν αποτεθεί πάνω σε αυτές τις αργίλους συνίστανται από αργιλώδεις-ιλυώδεις άμμους ή/και χάλικες. Το πρόγραμμα γεωερευνητικών εργασιών περιελάμβανε έναν σημαντικό αριθμό δειγματοληπτικών γεωτρήσεων, επί τόπου και εργαστηριακών δοκιμών. Τα στοιχεία του γεωερευνητικού προγράμματος αξιολογήθηκαν ώστε να κατανοηθεί καλύτερα το γεωλογικό προσομοίωμα της περιοχής του έργου και να διακριτοποιηθούν ζώνες με βάση τη συμπεριφορά των γεωυλικών κατά τη διάνοιξη της σήραγγας με μηχάνημα ολομέτωπης κοπής (ΤΒΜ). Όσον αφορά το μηχάνημα διάνοιξης, η επιλογή ενός μηχανήματος εδαφικής εξισορροπητικής πίεσης (ΕΡΒΜ) φαίνεται να είναι εύλογη τόσο από πλευράς ευστάθειας όσο και από πλευράς ρυθμού προχώρησης. Η επιλογή αυτή υπαγορεύεται από τα χαρακτηριστικά του εδάφους για την κάλυψη όλων των αντικειμενικών σκοπών όπως ο έλεγχος των καθιζήσεων και εδαφικών μετακινήσεων, η διατήρηση της στάθμης του υπόγειου νερού αλλά και η ικανοποιητική προχώρηση των σηράγγωνThe Thessaloniki Metropolitan Railway comprises two separate ~6 m diameter parallel tunnels with an ~8 km stretch each and 13 stations. The geology of the urban area of Thessaloniki is characterised by the presence of Neogene and Quaternary deposits. The base formation for the project area is a very stiff to hard red clay, dating to Upper Miocene-Pliocene. Upon this formation, Quaternary sediments have been deposited, most of which comprise sand and/or gravel in a clay-silt dominated matrix, covered in places by anthropogenic fill. Ground investigation campaigns incorporated a significant number of sampling boreholes and in situ and laboratory testing. This information was elaborated in order to obtain a better geological understanding and a geotechnical zonation of the ground with respect to mechanized tunnelling. EPB M appears to be the reasonable choice for the project in all aspects of tunnel safety and tunnelling performance. The characteristics and parameters of the soils and the hydrogeological regime directed towards this selection and it is expected that all the objectives, such as settlement and ground movements control, water table level maintenance and adequate performance, will be met by an EPBM provided it is properly operate

    Srs2 removes deadly recombination intermediates independently of its interaction with SUMO-modified PCNA

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    Saccharomyces cerevisiae Srs2 helicase plays at least two distinct functions. One is to prevent recombinational repair through its recruitment by sumoylated Proliferating Cell Nuclear Antigen (PCNA), evidenced in postreplication-repair deficient cells, and a second one is to eliminate potentially lethal intermediates formed by recombination proteins. Both actions are believed to involve the capacity of Srs2 to displace Rad51 upon translocation on single-stranded DNA (ssDNA), though a role of its helicase activity may be important to remove some toxic recombination structures. Here, we described two new mutants, srs2R1 and srs2R3, that have lost the ability to hinder recombinational repair in postreplication-repair mutants, but are still able to remove toxic recombination structures. Although the mutants present very similar phenotypes, the mutated proteins are differently affected in their biochemical activities. Srs2R1 has lost its capacity to interact with sumoylated PCNA while the biochemical activities of Srs2R3 are attenuated (ATPase, helicase, DNA binding and ability to displace Rad51 from ssDNA). In addition, crossover (CO) frequencies are increased in both mutants. The different roles of Srs2, in relation to its eventual recruitment by sumoylated PCNA, are discussed

    Epigenetics as a mechanism driving polygenic clinical drug resistance

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    Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

    Rapid unwinding of triplet repeat hairpins by Srs2 helicase of Saccharomyces cerevisiae

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    Expansions of trinucleotide repeats cause at least 15 heritable human diseases. Single-stranded triplet repeat DNA in vitro forms stable hairpins in a sequence-dependent manner that correlates with expansion risk in vivo. Hairpins are therefore considered likely intermediates during the expansion process. Unwinding of a hairpin by a DNA helicase would help protect against expansions. Yeast Srs2, but not the RecQ homolog Sgs1, blocks expansions in vivo in a manner largely dependent on its helicase function. The current study tested the idea that Srs2 would be faster at unwinding DNA substrates with an extrahelical triplet repeat hairpin embedded in a duplex context. These substrates should mimic the relevant intermediate structure thought to occur in vivo. Srs2 was faster than Sgs1 at unwinding several substrates containing triplet repeat hairpins or another structured loop. In contrast, control substrates with an unstructured loop or a Watson–Crick duplex were unwound equally well by both enzymes. Results with a fluorescently labeled, three-way junction showed that Srs2 unwinding proceeds unabated through extrahelical triplet repeats. In summary, Srs2 maintains its facile unwinding of triplet repeat hairpins embedded within duplex DNA, supporting the genetic evidence that Srs2 is a key helicase in Saccharomyces cerevisiae for preventing expansions

    A Role for PCNA Ubiquitination in Immunoglobulin Hypermutation

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    Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R) mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases

    Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption

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    The SRS2 (Suppressor of RAD Six screen mutant 2) gene encodes an ATP-dependent DNA helicase that regulates homologous recombination in Saccharomyces cerevisiae. Mutations in SRS2 result in a hyper-recombination phenotype, sensitivity to DNA damaging agents and synthetic lethality with mutations that affect DNA metabolism. Several of these phenotypes can be suppressed by inactivating genes of the RAD52 epistasis group that promote homologous recombination, implicating inappropriate recombination as the underlying cause of the mutant phenotype. Consistent with the genetic data, purified Srs2 strongly inhibits Rad51-mediated recombination reactions by disrupting the Rad51-ssDNA presynaptic filament. Srs2 interacts with Rad51 in the yeast two-hybrid assay and also in vitro. To investigate the functional relevance of the Srs2-Rad51 complex, we have generated srs2 truncation mutants that retain full ATPase and helicase activities, but differ in their ability to interact with Rad51. Importantly, the srs2 mutant proteins attenuated for Rad51 interaction are much less capable of Rad51 presynaptic filament disruption. An internal deletion in Srs2 likewise diminishes Rad51 interaction and anti-recombinase activity. We also present evidence that deleting the Srs2 C-terminus engenders a hyper-recombination phenotype. These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity
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