766 research outputs found
Three dimensional tracking with misalignment between display and control axes
Human operators confronted with misaligned display and control frames of reference performed three dimensional, pursuit tracking in virtual environment and virtual space simulations. Analysis of the components of the tracking errors in the perspective displays presenting virtual space showed that components of the error due to visual motor misalignment may be linearly separated from those associated with the mismatch between display and control coordinate systems. Tracking performance improved with several hours practice despite previous reports that such improvement did not take place
Early detection of melanoma metastases using microRNAs as novel biomarkers
Early detection of melanoma skin cancer, prior to metastatic spread, is critical to improve survival outcomes in patients. This study identified a melanoma-related panel of blood markers that can detect the presence of melanoma with high sensitivity and accuracy which is superior to currently used markers for melanoma progression, recurrence, and survival. Overall, the findings discussed in this thesis may lead to more precise measurement of disease progression allowing for better treatments and an increase in overall survival
SiDCoN: A Tool to Aid Scoring of DNA Copy Number Changes in SNP Chip Data
The recent application of genome-wide, single nucleotide polymorphism (SNP) microarrays to investigate DNA copy number aberrations in cancer has provided unparalleled sensitivity for identifying genomic changes. In some instances the complexity of these changes makes them difficult to interpret, particularly when tumour samples are contaminated with normal (stromal) tissue. Current automated scoring algorithms require considerable manual data checking and correction, especially when assessing uncultured tumour specimens. To address these limitations we have developed a visual tool to aid in the analysis of DNA copy number data. Simulated DNA Copy Number (SiDCoN) is a spreadsheet-based application designed to simulate the appearance of B-allele and logR plots for all known types of tumour DNA copy number changes, in the presence or absence of stromal contamination. The system allows the user to determine the level of stromal contamination, as well as specify up to 3 different DNA copy number aberrations for up to 5000 data points (representing individual SNPs). This allows users great flexibility to assess simple or complex DNA copy number combinations. We demonstrate how this utility can be used to estimate the level of stromal contamination within tumour samples and its application in deciphering the complex heterogeneous copy number changes we have observed in a series of tumours. We believe this tool will prove useful to others working in the area, both as a training tool, and to aid in the interpretation of complex copy number changes
The 'Melanoma-enriched' microRNA miR-4731-5p acts as a tumour suppressor
We previously identified miR-4731-5p (miR-4731) as a melanoma-enriched microRNA following comparison of melanoma with other cell lines from solid malignancies. Additionally, miR-4731 has been found in serum from melanoma patients and expressed less abundantly in metastatic melanoma tissues from stage IV patients relative to stage III patients. As miR-4731 has no known function, we used biotin-labelled miRNA duplex pull-down to identify binding targets of miR-4731 in three melanoma cell lines (HT144, MM96L and MM253). Using the miRanda miRNA binding algorithm, all pulled-down transcripts common to the three cell lines (n=1092) had potential to be targets of miR-4731 and gene-set enrichment analysis of these (via STRING v9.1) highlighted significantly associated genes related to the ‘cell cycle’ pathway and the ‘melanosome’. Following miR-4731 overexpression, a selection (n=81) of pull-down transcripts underwent validation using a custom qRT-PCR array. These data revealed that miR-4731 regulates multiple genes associated with the cell cycle (e.g. CCNA2, ORC5L, and PCNA) and the melanosome (e.g. RAB7A, CTSD, and GNA13). Furthermore, members of the synovial sarcoma X breakpoint family (SSX) (melanoma growth promoters) were also down-regulated (e.g. SSX2, SSX4, and SSX4B) as a result of miR-4731 overexpression. Moreover, this down-regulation of mRNA expression resulted in ablation or reduction of SSX4 protein, which, in keeping with previous studies, resulted in loss of 2D colony formation. We therefore speculate that loss of miR-4731 expression in stage IV patient tumours supports melanoma growth by, in part; reducing its regulatory control of SSX expression levels
Challenging cisgenderism through trans people's narratives of domestic violence and abuse
By drawing on empirical research that explored trans people’s experiences of domestic violence and abuse (DVA), this paper problematises the ‘gender asymmetry debate' in DVA discourse. It does so by highlighting cisgenderism and a heteronormative bias which have led to the invisibility of a trans perspective. Qualitative data was collected via narrative interviews and this was examined using a voice-centred relational technique. A total of twenty four interviews were undertaken with trans people (n = 15) and domestic abuse practitioners (n = 9). In relation to the presentation and impact of DVA, and in the context of trans and cisgender people's abuse experiences, the research findings report both similarities and differences. Four narratives are presented here to illuminate both. This paper adds new insight and challenges normative and dominant discourses by promoting the need for further theorising about the gendered nature of domestic violence and abuse
Use of Rollover Protective Structures -- Iowa, Kentucky, New York, and Ohio, 1992-1997
Agriculture has one of the highest occupational fatality rates of all industries in the United States (1). Tractors and other types of agricultural equipment account for a large proportion of these fatalities, and farm-tractor rollovers account for approximately 130 work-related deaths each year in the United States (2). Although rollover protective structures (ROPS) are effective in protecting tractor operators from fatal injuries during rollovers (3-5), most tractors in the United States are not equipped with ROPS (4-7). Beginning in 1985, tractor manufacturers in the United Sates agreed to sell only tractors with ROPS; however, many older tractors without ROPS remain in use. To determine the prevalence of the use of ROPS, beginning in 1992, the Farm Family Health and Hazard Surveillance (FFHHS) program * collected state-based data on tractor age and use of ROPS from selected states. As of August 1997, four states had completed collection and analysis of data on farm tractors. This report summarizes the results of that survey, which indicates that 80%-90% of tractors in use in the four states were manufactured before 1985 and that less than 40% are equipped with ROPS
Herschel/PACS observations of young sources in Taurus: the far-infrared counterpart of optical jets
Observations of the atomic and molecular line emission associated with jets
and outflows emitted by young stellar objects can be used to trace the various
evolutionary stages they pass through as they evolve to become main sequence
stars.
To understand the relevance of atomic and molecular cooling in shocks, and
how accretion and ejection efficiency evolves with the source evolutionary
state, we will study the far-infrared counterparts of bright optical jets
associated with Class I and II sources in Taurus (T Tau, DG Tau A, DG Tau B, FS
Tau A+B, and RW Aur).
We have analysed Herschel/PACS observations of a number of atomic ([OI]63um,
145um, [CII]158um) and molecular (high-J CO, H2O, OH) lines, collected within
the OTKP GASPS. To constrain the origin of the detected lines we have compared
the FIR emission maps with the emission from optical-jets and
millimetre-outflows, and the line fluxes and ratios with predictions from shock
and disk models.
All of the targets are associated with extended emission in the atomic lines
correlated with the direction of the optical jet/mm-outflow. The atomic lines
can be excited in fast dissociative J-shocks. The molecular emission, on the
contrary, originates from a compact region, that is spatially and spectrally
unresolved. Slow C- or J- shocks with high pre-shock densities reproduce the
observed H2O and high-J CO lines; however, the disk and/or UV-heated outflow
cavities may contribute to the emission.
While the cooling is dominated by CO and H2O lines in Class 0 sources, [OI]
becomes an important coolant as the source evolves and the environment is
cleared. The cooling and mass loss rates estimated for Class II and I sources
are one to four orders of magnitude lower than for Class 0 sources. This
provides strong evidence to indicate that the outflow activity decreases as the
source evolves.Comment: 18 pages, 9 figures, accepted by A&
Whole-exome sequencing of acquired nevi identifies mechanisms for development and maintenance of benign neoplasms
The melanoma transformation rate of each nevus is rare despite the detection of oncogenic BRAF or NRAS mutations in 100% of nevi. Acquired melanocytic nevi (AMN) do however mimic melanoma and ∼30% of all melanomas arise within pre-existing nevi. Using whole-exome sequencing of 30 matched nevi, adjacent normal skin, and saliva we sought to identify the underlying genetic mechanisms for nevus development. All nevi were clinically, dermoscopically, and histopathologically documented. In addition to identifying somatic mutations, we found mutational signatures relating to ultra-violet radiation (UVR) mirroring those found in cutaneous melanoma. In nevi we frequently observed the presence of the UVR mutation signature compared to adjacent normal skin (97% vs 10% respectively). In copy number aberration (CNA) analysis, in nevi with copy number loss of tumor suppressor genes (TSG), these were balanced by loss of potent oncogenes. Moreover, reticular and non-specific patterned nevi revealed an increased (
The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory
© 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss
Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions
The internally electrodynamic (IED) particle model was derived based on
overall experimental observations, with the IED process itself being built
directly on three experimental facts, a) electric charges present with all
material particles, b) an accelerated charge generates electromagnetic waves
according to Maxwell's equations and Planck energy equation and c) source
motion produces Doppler effect. A set of well-known basic particle equations
and properties become predictable based on first principles solutions for the
IED process; several key solutions achieved are outlined, including the de
Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass,
Einstein mass-energy relation, Newton's law of gravity, single particle self
interference, and electromagnetic radiation and absorption; these equations and
properties have long been broadly experimentally validated or demonstrated. A
specific solution also predicts the Doebner-Goldin equation which emerges to
represent a form of long-sought quantum wave equation including gravity. A
critical review of the key experiments is given which suggests that the IED
process underlies the basic particle equations and properties not just
sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200
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