307 research outputs found

    The influence of direct speech on the plot development and characterization in the Book of Judith

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    Although the Book of Judith has been thought to reflect a historical situation, this is not necessarily the case, and more recent literary critical studies have provided greater access to its intricacies. Judith contains a number of direct speeches, and direct speech in Hebrew literature in general, influences both plot development and characterization. This thesis is a discussion of how the direct speeches in Judith influence both its plot development and characterization. Since a number of the speeches contain irony, special attention has been given to this literary device

    Usability Evaluation of a Virtual Learning Environment : a University Case Study

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    As part of educational technology developments in Higher Education, every university has adopted a Virtual Learning Environment (VLE) that facilitates online methods of delivery by enabling the submission of course materials, course management system and computer-mediated communication. VLE is regarded as technology which is either accepted or rejected by its users such as students, academics and administrators. Perceived usefulness and ease of use play an important role in user acceptance and satisfaction. This paper provides quantitative results of usability evaluations i.e., the System Usability Scale (SUS) scores from different user groups including students (n=137), academics (n=23), administrators (n=19) and learning technologist (n=3). The qualitative element of the VLE evaluation comprised the utilization of an approach called Interactive Management (IM) (n=13). The results showed that the newly implemented VLE performed under the average usability expectation (SUS score of 58.6). Students on average evaluated the usability of the VLE higher than the staff. The usability scores of the students from different courses showed remarkable differences. The ranked and categorised feedback from the IM session highlights the importance of planning, training and communication before and during the implementation, as well as the aspect of usability and learnability of the VLE

    Complex Challenges and New Opportunities: Building the Framework for Boundary Review. An Assessment of PPS’s Organizational Readiness and Options for Citizen Engagement

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    On February 25, 2013, the PPS Board unanimously approved Resolution 4718, which directs staff “to develop and recommend a process for a comprehensive review of school boundaries district-wide and policies related to student assignment and transfer to better align with the Racial Educational Equity Policy and promote strong capture rates and academic programs at every grade level.” To deal with the student assignment and transfer policy issues, Superintendent Carole Smith charged the “Superintendent’s Advisory Committee on Enrollment and Transfer” (SACET) with recommending changes to student assignment and transfer policies to bring them into alignment with the district’s racial educational equity policy. As for the Districtwide Boundary Review component, in December 2013, Portland Public Schools entered into an Intergovernmental Agreement with the Center for Public Service (CPS) at Portland State University (PSU) to assist the District with eventually achieving two important tasks: Devise and implement a process to engage a wide range of current and future PPS parents, students and staff, community organizations; and other key stakeholders to conduct a comprehensive District-wide Boundary Review and recommend new PPS school boundaries for adoption by the Portland School Board; Create a flexible and dynamic “Boundary Review Framework” on which the current and future boundary-setting processes will be based. CPS proposed a three-phase approach for the “PPS District-Wide Boundary Framework” project, which would include recommendations at the end of each Phase as to recommended next steps. As initially outlined from the vantage point of October 2013, the proposed approach would be as follows: Phase I (3 months): Initial Assessment and Framework Recommendations Phase II (7-8 months): Stakeholder and Community Engagement Phase III (4 months): Final Recommendations, Community Deliberations, and Decision Making This report concludes Phase I and includes the Findings and Recommendations from our Initial Assessment

    Characterising standard genetic parts and establishing common principles for engineering legume and cereal roots

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    Plant synthetic biology and cereal engineering depends on the controlled expression of transgenes of interest. Most engineering in plant species to date has relied heavily on the use of a few, well-established constitutive promoters to achieve high levels of expression; however, the levels of transgene expression can also be influenced by the use of codon optimisation, intron-mediated enhancement and varying terminator sequences. Most of these alternative approaches for regulating transgene expression have only been tested in small-scale experiments, typically testing a single gene of interest. It is therefore difficult to interpret the relative importance of these approaches and to design engineering strategies that are likely to succeed in different plant species, particularly if engineering multi-genic traits where the expression of each transgene needs to be precisely regulated. Here we present data on the characterisation of 46 promoters and 10 terminators in Medicago truncatula, Lotus japonicus, Nicotiana benthamiana and Hordeum vulgare, as well as the effects of codon optimisation and intron-mediated enhancement on the expression of two transgenes in H. vulgare. We have identified a core set of promoters and terminators of relevance to researchers engineering novel traits in plant roots. In addition, we have shown that combining codon optimisation and intron-mediated enhancement increases transgene expression and protein levels in barley. Based on our study, we recommend a core set of promoters and terminators for broad use, and also propose a general set of principles and guidelines for those engineering cereal species

    Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets.

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    AIMS/HYPOTHESIS: Ageing is a major risk factor for development of metabolic diseases such as type 2 diabetes. Identification of the mechanisms underlying this association could help to elucidate the relationship between age-associated progressive loss of metabolic health and development of type 2 diabetes. We aimed to determine molecular signatures during ageing in the endocrine pancreas. METHODS: Global gene transcription was measured in pancreatic islets isolated from young and old rats by Ilumina BeadChip arrays. Promoter DNA methylation was measured by Sequenom MassArray in 46 genes that showed differential expression with age, and correlations with expression were established. Alterations in morphological and cellular processes with age were determined by immunohistochemical methods. RESULTS: Age-related changes in gene expression were found at 623 loci (>1.5-fold, false discovery rate [FDR] <5%), with a significant (FDR < 0.05) enrichment in genes previously implicated in islet-cell function (Enpp1, Abcc8), type 2 diabetes (Tspan8, Kcnq1), inflammatory processes (Cxcl9, Il33) and extracellular matrix organisation (Col3a1, Dpt). Age-associated transcriptional differences negatively correlated with promoter DNA methylation at several loci related to inflammation, glucose homeostasis, cell proliferation and cell-matrix interactions (Il33, Cxcl9, Gpr119, Fbp2, Col3a1, Dpt, Spp1). CONCLUSIONS/INTERPRETATION: Our findings suggest that a significant proportion of pancreatic islets develop a low-grade 'chronic' inflammatory status with ageing and this may trigger altered functional plasticity. Furthermore, we identified changes in expression of genes previously linked to type 2 diabetes and associated changes in DNA methylation that could explain their age-associated dysregulation. These findings provide new insights into key (epi)genetic signatures of the ageing process in islets.Biotechnology and Biological Sciences Research Council (Grant ID: BB/H003312/1), British Heart Foundation, FP6 Epigenome Network of Excellence programme, GlaxoSmithKline, Nuffield Foundation, Royal Society, Medical Research Council (Grant ID: MRC_MC_UU_12012/4)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00125-015-3837-

    Clear cell chondrosarcoma in Von Hippel-Lindau disease

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    A diagnosis of clear cell chondrosarcoma of the ulna was made in a patient with Von Hippel-Lindau disease (VHL). After surgery, genetic analysis of the tumor tissue showed loss of heterozygosity at the VHL gene locus. Immunohistochemical analysis confirmed loss of expression of the VHL protein in the tumor cells. In addition, abundant Cyclin D1 expression in the tumor was observed. Chondrosarcoma has been described before in a VHL patient and VHL protein expression has been correlated to tumor grade in a series of sporadic chondrosarcomas. In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of the VHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL

    A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

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    Background: Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. Methods: We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. Results: From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. Conclusions: It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting

    Von Hippel-Lindau Disease: Genetics and Role of Genetic Counseling in a Multiple Neoplasia Syndrome

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    Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndromes and is characterized by highly vascular tumors of the eyes, brain, and spine, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medullae and sympathetic paraganglia, endolymphatic sac, epididymis, and broad ligament. Since the discovery of the VHL gene in 1993, more than 900 families with VHL have been identified and examined. Genetic testing for VHL is widely available and will detect a disease-causing mutation in rate 95% to 100% of individuals who have a clinical diagnosis of VHL, making it the standard of care for diagnosis of VHL. Furthermore, genetic testing for VHL is indicated in some individuals with seemingly sporadic VHL-related tumor types, as ≤ 10% of pheochromocytoma or early-onset renal cell carcinoma and ≤ 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional features of VHL disease. The majority of VHL mutations are private, but there are also well-characterized founder mutations. VHL is a complex, multiorgan disease that spans the breadth of oncology subspecialties, and, as such, providers in these subspecialties should be aware of when to consider a diagnosis of VHL, when to refer a patient to a genetics specialist for consideration of gene testing, and, perhaps most importantly, how to communicate this sensitive information in an age-appropriate manner to at-risk families. This review will provide state-of-the-art information regarding the genetics of VHL and will serve as a key reference for nongenetics professionals who encounter patients with VHL.C.E. is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic, and an American Cancer Society Clinical Research Professor. RHG acknowledges the Dutch Kidney Foundation “KOUNCIL” consortium (CP11.13)
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