206 research outputs found
Building Quality Assurance into Metadata Creation: an Analysis based on the Learning Objects and e-Prints Communities of Practice
No full textThis paper challenges some of the assumptions underlying the metadata creation process in the context of two communities of practice, based around learning object repositories and open e-Print archives. The importance of quality assurance for metadata creation is discussed and evidence from the literature, from the practical experiences of repositories and archives, and from related research and practices within other communities is presented. Issues for debate and further investigation are identified, formulated as a series of key research questions. Although there is much work to be done in the area of quality assurance for metadata creation, this paper represents an important first step towards a fuller understanding of the subject.
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Investigating orthographic and semantic aspects of word learning in poor comprehenders
No full textThis study compared orthographic and semantic aspects of word learning in children who differed in reading comprehension skill. Poor comprehenders and controls matched for age (9–10 years), nonverbal ability and decoding skill were trained to pronounce 20 visually presented nonwords, 10 in a consistent way and 10 in an inconsistent way. They then had an opportunity to infer the meanings of the new words from story context. Orthographic learning was measured in three ways: the number of trials taken to learn to pronounce nonwords correctly, orthographic choice and spelling. Across all measures, consistent items were easier than inconsistent items and poor comprehenders did not differ from control children. Semantic learning was assessed on three occasions, using a nonword–picture matching task. While poor comprehenders showed equivalent semantic learning to controls immediately after exposure to nonword meaning, this knowledge was not well retained over time. Results are discussed in terms of the language and reading skills of poor comprehenders and in relation to current models of reading development
Characterising the Genetic Heterogeneity of Motor Neuron Disease in New Zealand
No full textMotor neuron disease (MND) is a group of neurodegenerative diseases which are characterized by adult-onset progressive degeneration of motor neurons, of which amyotrophic lateral sclerosis (ALS) is the most common form. MND has a complex aetiology with more than 40 genes discovered that are either directly causative of, or are associated with it, yet despite these identified causal genetic associations, only 5-10% of people with ALS have a Mendelian family history of disease (familial). Rather, the majority of cases appear in families where seemingly only a single individual is affected (sporadic) with disease. New Zealand has among the highest mortality and incidence rates in the world, yet to date no genetic studies have been undertaken in New Zealand to determine whether there is a genetic basis for this high rate of MND.
This thesis highlights the findings of the first large-scale genetic screening of MND genes in New Zealand. A total of 184 MND participants were genetically screened to identify causative variants. Autosomal dominant pathogenic variants were identified in 33/184 (17.9%) participants (24 C9orf72, 9 SOD1), with 12 of these being unaffected members of families with familial MND. One of the participants with C9orf72 repeat expansion was identified as unusual, having tested negative for the expansion by testing of blood DNA during life but whose brain DNA tested positive for pathogenic expansion. Repeat-primed PCR for the expansion revealed an atypical out-of-phase stutter, likely caused by a 2-5 bp insertion or deletion within the expanded allele. Subsequent neuropathological examination of the participant’s brain confirmed a genetic diagnosis of C9orf72. Cumulatively this case highlighted the importance of genetic variability and how this can affect common diagnostic techniques.
The genetic screen also uncovered fourteen variants of uncertain significance within the cohort in which the DCTN1:c.279+1G>C, p.? variant was further investigated. RNA sequencing of dermal fibroblasts from a participant with this variant confirmed the emergence of a novel -108 bp cryptic splice site within the mature mRNA of the proband. This altered splicing coupled with gene conservation and protein domain analysis is suggestive of re-classification of the variant to pathogenic, however, more investigation into whether DCTN1 haploinsufficiency is sufficient to cause MND.
Cumulatively, the results in this thesis are the first to help to explain some of the genetic heterogeneity present within a New Zealand MND cohort and could provide valuable insight into future directions and considerations for the genetic testing of MND in New Zealand
Art and the artist in the literary works of Elsa Triolet
No full textThis thesis takes a representative selection of Triolet's works to study the themes of writing and creativity as they are presented in the novels. These are all portraits of artists and the accounts of the search for a synthesis of aesthetic freedom and ethical responsibility. It considers Triolet's importance as a foreign writer, adopting a new creative language to be adopted by a different cultural
environment, to be essential in understanding her importance to the French literary tradition. By emphasising her formative years in the avant-garde circles of prerevolutionary Russia, my study demonstrates her considerable contribution to the meeting of Russian and French aesthetic theories. I extend this with close textual
readings of certain works to demonstrate her techniques in novelistic construction which reveal many Formalist practices before Formalist works in translation made
their official influence on creative methods.
The introduction considers the reasons for Triolet's neglect as a writer. It then considers various contemporary and recent critical appraisals which indicate
the interest she has received until present and which allow me to define my own critical approach. Part One traces Triolet's literary evolution from her formative
years in Russia, through exile to her first publications in Russian. It then considers her insertion into French literary activity, and her association with the schools of
socialist realism and the "nouveau roman".
Part Two examines two traditional novels which portray the creative and metaphorical roles of the artist and his work, showing the constant conflict between private and public lives. In Part Three, I show how aspects of novelistic
traditionalism are gradually foregrounded so that the work develops a dual-sided character where it both narrates and examines the processes of its own narration. In Part Four, this move to highly self-conscious aesthetics demonstrates an idiosyncratic exploration of new paths for the novel that bring visual, auditive and cinematographic media into the traditional domain of written art. Accompanying
the very post-modernist experimentation, I show how this research within the novel into the novel's own future has an ethical and redemptive purpose whose final conclusion is that creativity and human freedom are inexorably interwoven
The differentiated science achievement through 'group' and 'traditional' methods for ninth grades in the Sol C. Johnson Laboratory School, Savannah, Georgia, 1958 1959, 1959
No full textThe Translation of Inclusion/Acceptance, Accessibility, and Empathy with Online Community Engagement
No full textService-learning at Virginia Commonwealth University traditionally involves students performing community service to address community needs, coupled with guided reflection for holistic growth. In the spring of 2020 in-person courses were suspended due to the Covid-19 pandemic, necessitating a transition to online classes. This study aimed to determine if online service-learning provided the same benefits as in-person experiences, focusing on students\u27 perceptions of inclusion/acceptance, empathy, and accessibility. Online surveys were administered to students enrolled in service-learning courses during the semester. Results showed reduced levels of support compared to Fall 2019, but increased social activism and awareness. The study noted that remote learning may have affected accessibility and awareness of inequities. The author recommends that the university continues this line of research to better understand how the changes in higher education influence the practice of service-learning and related students and community members.
Author\u27s note
My name is Jessie Feng, a graduate of Virginia Commonwealth University in 2021, with a B.S. in Biology and minors in Chemistry and Psychology. Currently, I am working in the medical field, with aspirations of matriculating into medical school. My experiences as a Service-Learning Teacher’s Assistant inspired this project, as I first-hand witnessed the empowering impact of service-learning. With the onset of the pandemic and the subsequent transition to online courses, I found it imperative to explore whether these benefits could translate to online community engagement to ultimately assist in the strengthening of service-learning programs.
This piece has undergone substantial revisions for various purposes, this product was initially developed for the VCU Undergraduate Research and Creative Scholarship Summer Fellowship followed by the VCU Poster Symposium. From there, this project was revised for the 2021 Gulf South Summit, and now the VA Engage Journal. The final product is almost unrecognizable from my original submissions and I could not be more proud of this work. I am excited to share the results of this rewarding experience with a broader audience.
I could not have achieved this level of success without the support of my service-learning mentors at VCU: Dr. Amanda Hall, Prof Katie Elliott, and Prof Jill Reid. I am forever grateful for the opportunities and support they provided during my undergraduate career. Additionally, I would also like to thank my wonderful boyfriend, who constantly reminded me of why I took up these projects and never let me quit. Lastly, I would like to thank Dr. Steve Grande for his thorough feedback, meaningful discussions, and unwavering support throughout this publishing process.
All opinions expressed in this paper are my own and I have no conflicts of interest to disclose.
Correspondence concerning this article should be addressed to email: [email protected]
Atlantic Guardian, vol. 05, no. 03 (June 1948)
No full textThe challenge of education / Fred R. Emerson -- Something new has been added / Jessie B. Mifflin -- Newspapers of Newfoundland : The Twillingate Sun / John C. Loveridge -- Newfoundland Teachers' Association / S. J. Hefferton -- "A savings account for every child" / James Murdock -- He helped build a fleet / Richard A. White -- Document found in a bottle / Joel Nichols -- The Gosling Memorial Library -- Calling all motorists! -- Guardian angles -- Regional libraries -- Nfld. clubs abroad -- Stamps of Nfld.A popular magazine covering Newfoundland news and human interest stories with features such as Newfoundlanders Abroad, the Baby of the Month and community profiles, as well as poetry and short stories. Heavily illustrated with photographs. -- "Atlantic Guardian's platform: to make Newfoundland better known at home and abroad; to promote trade and travel in the Island; to encourage development of the Island's natural resources; to foster good relations between Newfoundland and her neighbors" (on all title pages after vol. 1, no. 4).Published monthly 1945-57, thereafter absorbed by the Atlantic Advocate (1952-92); suspended publication: October 1952-May 1953. Missing issues: vol. 14, nos. 7-8. -- An index to vols. 1-10 by author and/or article type is in vol. 11, no. 1 (January-February 1954), p. 33-48
Procaspase-3 activation as a strategy to overcome resistance to targeted anticancer therapies
No full textApoptotic signals are tightly regulated in cells to prevent accidental or unwanted cell death. In cancer cells, however, multiple defects exist in the apoptotic machinery to evade programmed cell death. Commonly reported defects include the overexpression of anti-apoptotic proteins (e.g. Bcl-2, FLIP, survivin, or inhibitor of apoptotic proteins (IAPs)) or the downregulation of pro-apoptotic proteins (e.g. death receptor or Apaf-1) to resist execution of apoptotic cell death by the executioner caspase (caspase-3). Paradoxically, the zymogen of the executioner caspase, procaspase-3, rather than being downregulated in cancer, has been found to be overexpressed in many cancers. In Chapter 1, I will describe the list of cancers that overexpress procaspase-3, before rationalizing this paradoxical observation. Finally, I will discuss emerging data from our laboratory in exploiting procaspase-3 overexpression as an anticancer strategy. In particular, I will outline the preclinical and clinical development of a selective procaspase-3 activating small molecule (PAC-1) as an anticancer therapy.
Activation of an executioner caspase such as caspase-3 leads to cleavage of hundreds of proteins in the cell, leading eventually to apoptotic cell death. In Chapter 2, I will first discuss the proteomic identification of caspase-3 substrates in whole cells treated with pro-apoptotic agents. Interestingly, two of the identified substrates of caspase-3, MEK1 and MEK2, are critical gatekeeper kinases in the mitogen-activated protein kinase (MAPK) pathway. Next, I will discuss the prevalence of oncogenic drivers in the MAPK pathway and the development of inhibitors as targeted anticancer therapeutics. Finally, I will explore the prospects of caspase-mediated degradation of MEK1/2 kinases as a strategy to overcome resistance to targeted therapies that inhibit kinases along the MAPK pathway.
One of the oncogenic driver mutations in the MAPK pathway is the V600E mutation on the BRAF protein. More than 50% of melanomas harbor this mutation that can be drugged with a BRAFV600E inhibitor vemurafenib. Chapter 3 reports the synergistic activity of PAC-1 + vemurafenib and PAC-1 + vemurafenib + trametinib in enhancing caspase-3 activity and apoptotic cell death in BRAFV600E melanoma cell lines. As a result of increased caspase-3 activity and resultant MEK1/2 degradation, the PAC-1 + vemurafenib combination induces significant reduction in tumor volume in a murine xenograft model of BRAFV600E melanoma, beyond the antitumor effects of the individual agents. In addition, the combination is also effective in significantly delaying the regrowth of cells after exposure to vemurafenib. Finally, PAC-1 remains effective in vemurafenib-resistant A375VR cells in culture and synergizes with vemurafenib to retard tumor growth of these cells in vivo.
In the MAPK pathway, kinases/GTPases upstream of the canonical effector kinase ERK1/2 are frequently mutated or altered. The BRAFV600E mutation discussed in Chapter 3, is a well-studied kinase that is mutated in the MAPK pathway. Besides BRAFV600E, EGFR, ALK, ABL, and RAS are oncogenes that are frequently altered in this pathway. While many mutant oncogenes have been identified, only mutations or alterations to EGFR, ALK, and ABL kinases can be targeted clinically by specific kinase inhibitions to elicit a therapeutic benefit. Chapter 4 describes my efforts to combine PAC-1 with kinase inhibitors targeting mutant EGFR, EML4-ALK, and BCR-ABL, to enhance apoptotic cell death and ultimately delay acquired resistance.
Given that PAC-1 is currently in a Phase I clinical trial (NCT02355535), and the kinase inhibitors used in Chapters 3 and 4 are already approved by the FDA, the preclinical data results presented herein can inform the design of future trials to investigate novel PAC-1 combination therapies in cancer patients.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-12-01The student, Jessie Peh, accepted the attached license on 2017-08-07 at 11:54.The student, Jessie Peh, submitted this Dissertation for approval on 2017-08-07 at 11:58.This Dissertation was approved for publication on 2017-08-09 at 13:16.DSpace SAF Submission Ingestion Package generated from Vireo submission #11594 on 2018-03-13 at 09:54:27Made available in DSpace on 2018-03-13T15:20:53Z (GMT). No. of bitstreams: 3
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