20 research outputs found
Developing mRNA-based biomarkers from formalin-fixed paraffin-embedded tissue
No full textCancer is a complex and heterogeneous disease which is one of the leading causes of death in Western civilisations. Thus, oncology is viewed as a primary focus for personalized medicine. It is recognised that cancer treatment needs to be better tailored in order to improve patient outcome. Patient tumor samples will be required to characterize cancer at a molecular level and identify where there may be disease subgroups that should be treated differently. The use of formalin-fixed paraffin-embedded tissue is important for enabling such studies. In this report, we focus on the challenges that have been faced to date along with the technological developments that have now made this possible. We also highlight the impact this may have on drug and diagnostic development.</p
The Colour Flows Back: Intention and Interpretation in Literature and in Everyday Action
No full textThe notion of the author’s intention is logically tied to the interpretation we give to her work as the notion of the agent’s intention is logically tied to the interpretation we give to her action. When we find a discrepancy between what the author or agent says and the meaning we find in her work or the sense we make of what she does, this does not show that the intention is irrelevant in determining this meaning or sense. As Frank Cioffi has argued, we are rather favouring one criterion of intention over another. Taking a close look at the early criticism surrounding The Turn of the Screw I draw attention to this phenomenon—much discussed by Wittgenstein—of favouring one criterion of intention over another. Because Wittgenstein’s views, though mentioned frequently, are still ill-understood, I go on to tease out the philosophical assumptions that lurk in the background of disputes about the relevance of intention for interpretation
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Investigating Material Degradation Through the Recycling of PLA in Additively Manufactured Parts
No full textThe field of additive manufacturing (AM) has been expanding rapidly with the decreasing cost
of desktop-scale material extrusion AM systems. As the cost of AM systems decreases, more users
are investing in the technology, including universities, which have turned to AM as an option for
providing wide-scale access to prototyping technology. However, this type of wide-access printing
generates significant waste due to cast-off support material as well as failed prints from
inexperienced users. This paper investigates the feasibility of recycling this cast-off material
through the relationship between the mechanical properties of recycled PLA and the number of
lifecycles it has experienced on a desktop material extrusion machine. A three-stage pelletizing,
extrusion, and printing process is used to investigate recycling of PLA material from cast-off build
material. Additionally, the research investigates how adding virgin pellets to pellets of the recycled
material in various ratios can affect tensile properties.Mechanical Engineerin
Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues
No full textBackground: More than 20% of human transcripts have naturally occurring antisense products (or natural antisense transcripts – NATs), some of which may play a key role in a range of human diseases. To date, several databases of in silico defined human sense-antisense (SAS) pairs have appeared, however no study has focused on differential expression of SAS pairs in breast tissue. We therefore investigated the expression levels of sense and antisense transcripts in normal and malignant human breast epithelia using the Affymetrix HG-U133 Plus 2.0 and Almac Diagnostics Breast Cancer DSA microarray technologies as well as massively parallel signature sequencing (MPSS) data.
Results: The expression of more than 2500 antisense transcripts were detected in normal breast duct luminal cells and in primary breast tumors substantially enriched for their epithelial cell content by DSA microarray. Expression of 431 NATs were confirmed by either of the other two technologies. A corresponding sense transcript could be identified on DSA for 257 antisense transcripts. Of these SAS pairs, 163 have not been previously reported. A positive correlation of differential expression between normal and malignant breast samples was observed for most SAS pairs. Orientation specific RT-QPCR of selected SAS pairs validated their expression in several breast cancer cell lines and solid breast tumours.
Conclusion: Disease-focused and antisense enriched microarray platforms (such as Breast Cancer DSA) confirm the assumption that antisense transcription in the human breast is more prevalent than previously anticipated. Expression of a proportion of these NATs has already been confirmed by other technologies while the true existence of the remaining ones has to be validated. Nevertheless, future studies will reveal whether the relative abundances of antisense and sense transcripts have regulatory influences on the translation of these mRNAs
Phacidiaceae endophytes of Picea rubens in Eastern Canada
No full textMore than 100 fungal endophyte strains belonging to the family Phacidiaceae were isolated from surface-sterilized Picea rubens needles collected from the Acadian Forest Region in New Brunswick, Canada. Strains were characterized morphologically by their asexual states and phylogenetic analyses were conducted using the nuclear internal transcribed spacer rDNA (ITS) marker and the second largest subunit of ribosomal polymerase II (RPB2). Morphological and phylogenetic data revealed seven species: Darkera cf. parca, Strasseria geniculata, two novel Phacidium species, P. dicosmoanum and P. faciforme, and three novel monotypic genera described to accommodate distinct species: Calvophomopsis rubenticola, Cornibusella ungulata, and Gloeopycnis protuberans. Further analyses of Darkera spp. were performed with ITS and partial translation elongation factor 1-Îą (TEF1Îą), suggesting D. parca is a species complex. Phacidiaceae includes hundreds of known species that are unrepresented by sequence data; therefore, ITS markers were generated from herbarium material including type specimens of Darkera parca, Phacidium lunatum, and specimens of Allantophomopsiella, Allantophomopsis, Bulgaria, Phacidium, and Pseudophacidium species. The description of novel species combined with morphological observations and reference sequences will facilitate the identification of conifer endophytes, both from specimens or cultures and in environmental sequence data, and improve our understanding of this large and mostly neglected family.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Lophodermium resinosum sp. nov. from red pine (Pinus resinosa) in Eastern Canada
No full textA morphologically distinct Lophodermium species was collected from fallen secondary needles of Pinus resinosa over two consecutive years in Eastern Ontario; subsequent herbarium studies confirmed its presence in Nova Scotia, Quebec, and Maine. Symptomatic needles frequently exhibited red bands and completely subepidermal ascomata and conidiomata. Ascospore isolates from specimens were used to reconstruct phylogenies inferred from internal transcribed spacer rDNA and partial actin gene sequences. Both phylogenetic analyses delineated the specimens from other sequenced Lophodermium species. Phylogenetic evidence combined with morphological characters of ascomata and conidiomata supported the distinctiveness of this species, described here as Lophodermium resinosum sp. nov.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
on Vancouver Island, British Columbia, Canada
No full textGarry oak (Quercus garryana) is the only oak native to British Columbia (BC), where it occupies the northernmost extent of its range. The ecosystem it occupies in BC has been greatly reduced in size and fragmented by European settlement. Garry oak forms ectomycorrhizas that are essential to its existence and will likely play an important role in the response of this tree to climate change. Yet, relatively little is known about the ectomycorrhizal fungi associated with Garry oak in BC. In this study we have documented the occurrence of fungi forming ectomycorrhizas with Garry oak at six locations on Vancouver Island by sequencing the ITS region of ectomycorrhizal root tips collected from Garry oak stands. Of the 47 species we detected, only about 20% can be confidently assigned to known species because not all species have been sequenced and many sequences in public databases are incorrectly or incompletely identified, but the majority of them belong to a community of fungi associated primarily with oaks or other members of Fagaceae. The uniqueness of this community of ectomycorrhizal fungi indicates that the possible expansion of the range of Garry oak in BC in response to climate change may be limited by the co-migration of its ectomycorrhizal fungi.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
The Self and Social Relations
No full textThe central subject of this thesis is the nature of the self. I argue against an atomistic conception which takes the human self to exist self-sufficiently and prior to social relations, and in favour of a holistic conception which takes the self to be constitutively dependent on social relations. I defend this view against criticisms that a holistic account undermines the need for what I call 'critical distance' between subjects and their communities. This involves answering the charges that such constitutive dependence: 1) removes the possibility for individuals to determine themselves freely apart from the communities in which they engage; and 2) deprives us of an external standard with which to engage critically with those constitutive communities.
I argue that the above criticisms are encouraged by reliance on a certain epistemological picture. This picture involves a foundationalist construal of knowledge that ultimately depends on a notion of an immediately given epistemic content that can serve to give us an absolute conception of an objective reality with which we can do away with partial or relative conceptions of ourselves and the world we inhabit. It is this that leads the critic to demand a standard external to communities, which in turn encourages a notion of the self and freedom that can ultimately be grounded apart from the "distortions" of social practice.
I directly attack the notion of an immediately given epistemic content through a series of transcendental arguments, showing that the condition of possibility for our forming any conception of ourselves or the world is participation in social forms of life. I further argue that properly human identities are essentially shaped by the self-conceptions these forms of life make available to us. Since freedom can no longer depend on radical detachment, I offer a new account of freedom as a social achievement, based on a notion of rational progress which allows us to develop ourselves and our social world critically, drawing only on those standards available within our practices.
With the notion of an immediately given epistemic content undermined, I have shown not only that freedom and rational progress are consistent with a holistic account, but that in fact they depend on such a holistic account
Insights into Antidepressant Prescribing Using Open Health Data
No full textThe growth of big data is transforming many economic sectors, including the medical and healthcare sector. Despite this, research into the practical application of data analytics to the development of health policy is still limited. In this study we examine how data science and machine learning methods can be applied to a variety of open health datasets, including GP prescribing data, disease prevalence data and economic deprivation data. This paper discusses the context of mental health and antidepressant prescribing in Northern Ireland and highlights its importance as a public policy issue. A hypothesis is proposed, suggesting that the link between antidepressant usage and economic deprivation is mediated by depression prevalence. An analysis of various heterogeneous open datasets is used to test this hypothesis. A description of the methodology is provided, including the open health datasets under investigation and an explanation of the data processing pipeline. Correlations between key variables and several different clustering analyses are presented. Evidence is provided which suggests that the depression prevalence hypothesis is flawed. Clusters of GP practices based on prescribing behaviour and disease prevalence are described and key characteristics are identified and discussed. Possible policy implications are explored and opportunities for future research are identified.<br/
Towards the Integration of Prescription Analytics into Health Policy and General Practice
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