396 research outputs found

    A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

    No full text
    The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

    Functional identification and mapping of a gene that represses telomerase hTERT transcription in prostate cancer cells

    No full text
    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Telomerase is present in over 90% of tumour tissues and immortalized cells and is tightly regulated in most normal somatic cells. This suggests the existence of regulatory mechanisms repressing telomerase in normal cells that somehow have become inactive during cancer development. In this project, I used genetic complementation in the form of microcell-mediated monochromosome transfer (MMCT) to search for chromosomes that repress telomerase activity in a prostate cancer cell line, PC-3. Microcell hybrids generated by introducing normal human chromosome 11 strongly inhibited telomerase. Telomerase is regulated primarily at the level of hTERT transcription, its catalytic subunit. Consequently, endogenous hTERT mRNA levels were measured by quantitative RT-PCR in microcell hybrids generated by transferring normal human chromosomes into a PC-3 sub-clone (PC- 3/hTERT) ectopically expressing hTERT cDNA to prevent senescence. Only hybrids constructed with transferred chromosome 11 showed strong transcriptional repression of hTERT. Next, hybrids were constructed by the MMCT transfer of chromosome 11 fragments (X-ray-induced). FISH analysis of clones with completely silenced endogenous hTERT transcription revealed in all cases a discrete chromosome 11 fragment with both the p-arm and q-arm material. A randomly selected hTERT-repressed clone was treated with ganciclovir to select against the HyTK marker and reverse the phenotype. hTERT expression in majority of GCV-resistant clones returned to levels comparable to the parent PC-3/hTERT cells. Collectively, these results provide strong functional evidence for the presence of a powerful telomerase repressor sequence on the fragment. Transfer of one repressive fragment back into mouse A9 cells was then carried out to facilitate fine-structure mapping of its sequence content. High density STS mapping of the fragment in each of the clones revealed a considerable DNA content heterogeneity across the panel. These content maps, together with a further round of MMCT to confirm hTERTrepressive activity, enabled me to identify three candidate regions on the q-arm of chromosome 11 where the repressor sequence may be located: the first region lies between map positions 64.70Mb to 65.42Mb and the other two regions each flank a single positive STS marker at 69.71Mb and 127.32Mb. KAT5, a histone modifying gene has been identified as a potential candidate for repressing hTERT.Professor Robert F Newbol

    Editorial Board

    No full text
    Editors-in Chief Travis B. Dye A. Diana Holcombe Production Editors Carolynn Fagan Cory O’Neill Cathleen O. Sohlberg Managing Editor Robert E. Henderson Staff Michael Begley Alanah Griffith Taud Hume Michael M. Lawlor Shane P. McGovern Peter W. Mickelson Chris L. Newbold Reid Perkins Bryan L. Quick Mathew Stevenson Faculty Advisor J. Martin Burk

    A comprehensive approach to health literacy: validating the All Aspects of Health Literacy Scale in a respresentative sample of Arabic-speaking adult Syrian refugees

    No full text
    MASTER OF SCIENCE (2017), McMaster University, Hamilton ON (Department of Global Health) TITLE: A comprehensive approach to health literacy: validating the all aspects of health literacy scale (AAHLS) in a representative sample of Arabic-speaking adult Syrian refugees AUTHOR: Raafia Siddiqui, BSc Hons. (York University, 2014) SUPERVISOR: Dr. K. Bruce Newbold NUMBER OF PAGES: vii, 92The purpose of this study is to quantify current health literacy levels amongst a segment of the Syrian refugee population in Canada by translating and validating an existing comprehensive health literacy assessment tool, the All Aspects of Health Literacy Scale (AAHLS) into Arabic. This study (1) determined functional, communicative and critical health literacy levels amongst Syrian refugees. Functional and critical health literacy was comparatively low but respondents seemed able to effectively communicate with their providers and access supports to read and fill in health documents. Significant correlates of low health literacy were presence of long-term health conditions and place of origin (country versus refugee camp). This study also validated the AAHLS in Arabic-speaking Syrian refugees, with a Cronbach’s alpha of 0.67 for the overall scale and 0.63 for health literacy items. The overall scale had high content validity. The feasibility of this instrument as a self-administered screening tool in clinical or community settings was demonstrated with a high response rate of 0.86.ThesisMaster of Science (MSc)Health literacy looks at an individual's ability to read, understand and interpret health information and ultimately use it to exert greater control over their health. The purpose of this study is to understand the factors that influence health literacy levels amongst a segment of the Syrian refugee population in Canada by translating and validating an existing comprehensive health literacy assessment tool, the All Aspects of Health Literacy Scale (AAHLS) into Arabic. This study (1) determined functional (reading and filling in health documents), communicative (speaking to health providers) and critical health (assessing the relevance and appropriateness of health information) literacy levels amongst Syrian refugees. Functional and critical health literacy was comparatively low but respondents seemed able to effectively communicate with their providers and access supports to read and fill in health documents. Low health literacy was associated with having a long-term health conditions and staying in a refugee camp. This study found the translated AAHLS to be reliable, with a Cronbach’s alpha of 0.67 for the overall scale and 0.63 for health literacy items. The overall scale had high content validity. The feasibility of this instrument as a self-administered screening tool in clinical or community settings was demonstrated with a high response rate of 0.86

    Perpetual Access Machines: Archiving Web-Published Scholarship at Scale

    No full text
    In 2018, the Internet Archive undertook a large-scale project to build as complete a collection as possible of scholarly outputs published on the web, as well as to improve the discoverability and accessibility of scholarly works archived as part of these global web harvests. This project involved a number of areas of work: targeted archiving of known OA publications (especially at-risk “long tail” publications); extraction and augmentation of bibliographic metadata and full text; integration and preservation of related identifier, registry, and aggregation services and datastores; partnerships with affiliated initiatives and joint service developments; and creation of new tools and machine learning approaches for identifying archived scholarly work in existing born-digital and web collections. The project also identified and archived associated research outputs such as blogs, datasets, code repositories and other secondary research objects. The beta API and public interface - code-named "fatcat" - can be found at https://fatcat.wiki/. Project leads will talk about the project’s current status and upcoming work, focusing on content acquisition, indexing, discoverability, the role of machine learning, service provisioning, and their collaborative work with libraries, publishers, and non-profits. Conceptually, the project demonstrates that the scalability and technologies of "archiving the web" can facilitate automated ingest, enrichment, and dissemination strategies for a variety of web-published primary and secondary scholarly record types that have traditionally been collected via more custom and manual workflows. The project strategic goal is to provide open infrastructure for the perpetual discoverability of and access to archived scholarship.</p

    Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

    No full text
    This ESMO Clinical Practice Guidelines provide updated state-of-the-art recommendations on management of thyroid cancer (diagnosis, treatment and follow-up), compiled by a multidisciplinary author panel and accompanied by level of evidence and grade of recommendation, depending on the strength of supporting data and magnitude of benefit from particular intervention

    The role of Plasmodium falciparum var genes in malaria in pregnancy

    No full text
    Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is responsible for many of the harmful effects of malaria during pregnancy. Sequestration occurs as a result of parasite adhesion molecules expressed on the surface of infected erythrocytes binding to host receptors in the placenta such as chondroitin sulphate A (CSA). Identification of the parasite ligand(s) responsible for placental adhesion could lead to the development of a vaccine to induce antibodies to prevent placental sequestration. Such a vaccine would reduce the maternal anaemia and infant deaths that are associated with malaria in pregnancy. Current research indicates that the parasite ligands mediating placental adhesion may be members of the P. falciparum variant surface antigen family PfEMP1, encoded by var genes. Two relatively well-conserved subfamilies of var genes have been implicated in placental adhesion, however, their role remains controversial. This review examines the evidence for and against the involvement of var genes in placental adhesion, and considers whether the most appropriate vaccine candidates have yet been identified

    Structural change and unit roots

    No full text
    This thesis contains a discussion of three problems related to structural changes and unit-roots in time-series analysis. First, it is shown under which conditions it is possible to consistently estimate the break date in a model with one structural break. It is also shown that when the errors have a unit-root, it is possible to spuriously estimate a break when there is none. Second, the same issues are discussed with respect to estimating the number of breaks. Finally, it is considered the problem of testing for unit-roots in the presence of structural breaks. New evidence is presented for the Nelson-Plosser macroeconomic data that strongly weaken recent results that reject the unit-root hypothesis for these series.Made available in DSpace on 2011-05-07T14:25:05Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9512500.pdf: 2461526 bytes, checksum: fe5fe2dabb524957c960f52ab4b49e77 (MD5) Previous issue date: 1994Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding ([email protected]) on 2011-05-07T15:06:29Z Item is restricted indefinitely.Restriction data tranferred 2014-07-01T11:31:55-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permissionETDs are only available to UIUC Users without author permissionU of I Onl

    CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

    No full text
    The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-valu

    State-dependent model, multi-step-ahead, multiple forecasts: Experience with the United States unemployment rate series

    No full text
    This study develops a framework for the fitting, analysis, and forecasting of linear and nonlinear time series models. Through Priestley's State Dependent Model and the Kalman filter algorithm, linear, nonlinear and nonstationary models have been fitted to the US unemployment rate series. The algorithm has been extended to account for both nonlinearity and nonstationarity. Also, some of the existing tests for linearity in the time domain have been applied and indicate the existence of bilinear type nonlinearity in the series. Models fitted in the state dependent framework and the bilinear models have been used for one to twelve step ahead forecasting. The models fitted in the state dependent framework outperform other models, and the bilinear models outperform the linear model. The performance of the existing forecast accuracy comparison tests has been analyzed empirically and through simulation. An alternative to the Diebold and Mariano test has been suggested, which appears to have better size than the Diebold and Mariano test.Made available in DSpace on 2011-05-07T12:51:49Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9503289.pdf: 3339843 bytes, checksum: 0ac8c6e43f34b9975013a2de81ca0ca8 (MD5) Previous issue date: 1994Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding ([email protected]) on 2011-05-07T14:46:53Z Item is restricted indefinitely.Restriction data tranferred 2014-07-01T11:21:06-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permissionETDs are only available to UIUC Users without author permissionU of I Onl
    corecore