750 research outputs found
Is Hypermedia an Effective Tool for Education
Whilst there has been much mention in the literature recently concerning the development of hypermedia systems, there is very little reported work on projects to assess their effectiveness, or otherwise, in education. This paper reports on a project currently underway at the University of Southampton in the UK to develop a hypertext interface for an interactive videodisc application in biology education, and to undertake a thorough evaluation of the resulting system as used by undergraduate students at the University. The system is currently based on Apple's Hypercard and uses existing videodisc material. INTRODUCTION 1. 1 Introduction Until very recently, the costs of both hardware and software made the use of interactive videodisc (IV) systems virtually non-existent in education. Most examples of interactive video material were in the industrial training sector, where it can be very cost effective as well as educationally effective to produce videodiscs and related software designe..
Implementing an Open Link Service for the World Wide Web
Links are the key element for changing a text into a hypertext, and yet the WWW provides limited linking facilities. Modelled on Open Hypermedi
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Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity.
Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, n = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, n = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aβ42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aβ40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells in vitro. These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI
Alpha6beta4 integrin crosslinking induces EGFR clustering and promotes EGF-mediated Rho activation in breast cancer
<p>Abstract</p> <p>Background</p> <p>The α6β4 integrin is overexpressed in the basal subtype of breast cancer and plays an important role in tumor cell motility and invasion. EGFR is also overexpressed in the basal subtype of breast cancer, and crosstalk between α6β4 integrin and EGFR appears to be important in tumor progression.</p> <p>Methods</p> <p>We evaluated the effects of α6β4 crosslinking on the distribution and function of EGFR in breast carcinoma cell line MDA-MB-231. Receptor distribution was evaluated by fluorescence microscopy and multispectral imaging flow cytometry, and ligand-mediated EGFR signaling was evaluated using Western blots and a Rho pull-down assay.</p> <p>Results</p> <p>Antibody-mediated crosslinking of α6β4 integrin was sufficient to induce cell-surface clustering of not only α6β4 but also EGFR in nonadherent cells. The induced clustering of EGFR was observed minimally after 5 min of integrin crosslinking but was more prominent after 15 min. EGFR clustering had minimal effect on the phosphorylation of Akt or Erk1,2 in response to EGF in suspended cells or in response to HB-EGF in adherent cells. However, EGFR clustering induced by crosslinking α6β4 had a marked effect on Rho activation in response to EGF.</p> <p>Conclusion</p> <p>Crosslinking α6β4 integrin in breast carcinoma cells induces EGFR clustering and preferentially promotes Rho activation in response to EGF. We hypothesize that this integrin-EGFR crosstalk may facilitate tumor cell cytoskeletal rearrangements important for tumor progression.</p
Getting clean drinking water into remote Indigenous communities means overcoming city thinking
The First Detections of the Extragalactic Background Light at 3000, 5500, and 8000A (III): Cosmological Implications
(Abridged) We have used HST WFPC2 and ground-based spectroscopy to measure
the integrated extragalactic background light (EBL) at optical wavelengths. We
have also computed the integrated light from individual galaxy counts in the
images used to measure the EBL and in the Hubble Deep Field. We find that the
flux in galaxies as measured by standard galaxy photometry methods has
generally been underestimated by about 50%. Further, we find that the total
flux in individually detected galaxies is a factor of 2 to 3 less than the EBL
at 3000--8000A. We show that a significant fraction of the EBL may come from
normal galaxies at z<4, which are simply undetectable as a result of
K-corrections and cosmological surface brightness dimming. This is consistent
with recent redshift surveys at z<4. In the context of some simple models, we
discuss the constraints placed by the EBL on the evolution of the luminosity
density at z>1. Based on our optical EBL and published UV and IR EBL
measurements, we estimate that the total EBL from 0.1--1000 microns is 100+/-20
nW/m^2/sr. If the total EBL were produced entirely by stellar nucleosynthesis,
then we estimate that the total baryonic mass processed through stars is
Omega_* = 0.0062 (+/- 0.0022) h^{-2}, which corresponds to 0.33+/-0.12 Omega_B
for currently favored values of the baryon density. This estimate is smaller by
roughly 7% if 7 h_{0.7} nW/m^2/sr of the total EBL comes from accretion onto
central black holes. This estimate of Omega_* suggests that the universe has
been enriched to a total metal mass of 0.21(+/-0.13) Z_sun Omega_B. Our
estimate is consistent with other measurements of the cumulative metal mass
fraction of stars, stellar remnants, and the intracluster medium of galaxy
clusters in the local universe.Comment: Accepted for publication in ApJ, 20 pages using emulateapj.sty,
version with higher resolution figures available at
http://www.astro.lsa.umich.edu/~rab/publications.html or at
http://nedwww.ipac.caltech.edu/level5/Sept01/Bernstein3/frames.htm
Shaping electron wave functions in a carbon nanotube with a parallel magnetic field
A magnetic field, through its vector potential, usually causes measurable
changes in the electron wave function only in the direction transverse to the
field. Here we demonstrate experimentally and theoretically that in carbon
nanotube quantum dots, combining cylindrical topology and bipartite hexagonal
lattice, a magnetic field along the nanotube axis impacts also the longitudinal
profile of the electronic states. With the high (up to 17T) magnetic fields in
our experiment the wave functions can be tuned all the way from "half-wave
resonator" shape, with nodes at both ends, to "quarter-wave resonator" shape,
with an antinode at one end. This in turn causes a distinct dependence of the
conductance on the magnetic field. Our results demonstrate a new strategy for
the control of wave functions using magnetic fields in quantum systems with
nontrivial lattice and topology.Comment: 5 figure
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Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.
BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes
A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation
BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users
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