3,061 research outputs found
Teaching and learning in virtual worlds: Is it worth the effort?
Educators have been quick to spot the enormous potential afforded by virtual worlds for situated and authentic learning, practising tasks with potentially serious consequences in the real world and for bringing geographically dispersed faculty and students together in the same space (Gee, 2007; Johnson and Levine, 2008). Though this potential has largely been realised, it generally isn't without cost in terms of lack of institutional buy-in, steep learning curves for all participants, and lack of a sound theoretical framework to support learning activities (Campbell, 2009; Cheal, 2007; Kluge & Riley, 2008). This symposium will explore the affordances and issues associated with teaching and learning in virtual worlds, all the time considering the question: is it worth the effort?. Ā© 2010 Helen Farley, Sue Gregory, Allan Ellis, Geoffrey Crisp, Jenny Grenfell, Angela Thomas & Mathew Campbell
Lattice worldline representation of correlators in a background field
We use a discrete worldline representation in order to study the continuum
limit of the one-loop expectation value of dimension two and four local
operators in a background field. We illustrate this technique in the case of a
scalar field coupled to a non-Abelian background gauge field. The first two
coefficients of the expansion in powers of the lattice spacing can be expressed
as sums over random walks on a d-dimensional cubic lattice. Using combinatorial
identities for the distribution of the areas of closed random walks on a
lattice, these coefficients can be turned into simple integrals. Our results
are valid for an anisotropic lattice, with arbitrary lattice spacings in each
direction.Comment: 54 pages, 14 figure
Supernova 2007bi as a pair-instability explosion
Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse
progressively heavier elements in their centres, up to inert iron. The core
then gravitationally collapses to a neutron star or a black hole, leading to an
explosion -- an iron-core-collapse supernova (SN). In contrast, extremely
massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores
which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at
relatively low densities. Conversion of energetic, pressure-supporting photons
into electron-positron pairs occurs prior to oxygen ignition, and leads to a
violent contraction that triggers a catastrophic nuclear explosion. Tremendous
energies (>~ 10^{52} erg) are released, completely unbinding the star in a
pair-instability SN (PISN), with no compact remnant. Transitional objects with
100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse
supernovae following violent mass ejections, perhaps due to short instances of
the pair instability, may have been identified. However, genuine PISNe, perhaps
common in the early Universe, have not been observed to date. Here, we present
our discovery of SN 2007bi, a luminous, slowly evolving supernova located
within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding
core mass to be likely ~100 M_{solar}, in which case theory unambiguously
predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were
synthesized, and that our observations are well fit by PISN models. A PISN
explosion in the local Universe indicates that nearby dwarf galaxies probably
host extremely massive stars, above the apparent Galactic limit, perhaps
resulting from star formation processes similar to those that created the first
stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009),
including all supplementary informatio
Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae
Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity
BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors
<p>Abstract</p> <p>Background</p> <p>The prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare.</p> <p>Methods</p> <p>We performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m<sup>2 </sup>BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model.</p> <p>Results</p> <p>The median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off).</p> <p>Conclusion</p> <p>In summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.</p
Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders
Increasing evidence suggests that epigenetic factors have critical roles in gene
regulation in neuropsychiatric disorders and in aging, both of which are
typically associated with a wide range of gene expression abnormalities. Here,
we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated
histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated
with transcriptionally active chromatin, at the promoter regions of eight
schizophrenia-related genes in n=82 postmortem prefrontal
cortical samples from normal subjects and those with schizophrenia and bipolar
disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with
gene expression levels, as measured by real-time qPCR for several genes,
including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine
receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70
homolog A (TOMM70A) and protein phosphatase 1E (PPM1E).
Ac-H3K9K14 levels of several of the genes tested were significantly negatively
associated with age in normal subjects and those with bipolar disorder, but not
in subjects with schizophrenia, whereby low levels of histone acetylation were
observed in early age and throughout aging. Consistent with this observation,
significant hypoacetylation of H3K9K14 was detected in young subjects with
schizophrenia when compared with age-matched controls. Our results demonstrate
that gene expression changes associated with psychiatric disease and aging
result from epigenetic mechanisms involving histone acetylation. We further find
that treatment with a histone deacetylase (HDAC) inhibitor alters the expression
of several candidate genes for schizophrenia in mouse brain. These findings may
have therapeutic implications for the clinical use of HDAC inhibitors in
psychiatric disorders
Genetics of callous-unemotional behavior in children
Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase āmissing heritabilityā was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU
Coverage, Continuity and Visual Cortical Architecture
The primary visual cortex of many mammals contains a continuous
representation of visual space, with a roughly repetitive aperiodic map of
orientation preferences superimposed. It was recently found that orientation
preference maps (OPMs) obey statistical laws which are apparently invariant
among species widely separated in eutherian evolution. Here, we examine whether
one of the most prominent models for the optimization of cortical maps, the
elastic net (EN) model, can reproduce this common design. The EN model
generates representations which optimally trade of stimulus space coverage and
map continuity. While this model has been used in numerous studies, no
analytical results about the precise layout of the predicted OPMs have been
obtained so far. We present a mathematical approach to analytically calculate
the cortical representations predicted by the EN model for the joint mapping of
stimulus position and orientation. We find that in all previously studied
regimes, predicted OPM layouts are perfectly periodic. An unbiased search
through the EN parameter space identifies a novel regime of aperiodic OPMs with
pinwheel densities lower than found in experiments. In an extreme limit,
aperiodic OPMs quantitatively resembling experimental observations emerge.
Stabilization of these layouts results from strong nonlocal interactions rather
than from a coverage-continuity-compromise. Our results demonstrate that
optimization models for stimulus representations dominated by nonlocal
suppressive interactions are in principle capable of correctly predicting the
common OPM design. They question that visual cortical feature representations
can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure
Reduced prefrontal gyrification in obsessiveācompulsive disorder
Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessiveācompulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (pĀ =Ā 0.021) and a trend for a decreased A-GI in the right hemisphere (pĀ =Ā 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease
Heritability of non-speech auditory processing skills
Recent insight into the genetic bases for autism spectrum disorder, dyslexia, stuttering, and language disorders suggest that neurogenetic approaches may also reveal at least one etiology of auditory processing disorder (APD). A person with an APD typically has difficulty understanding speech in background noise despite having normal pure-tone hearing sensitivity. The estimated prevalence of APD may be as high as 10% in the pediatric population, yet the causes are unknown and have not been explored by molecular or genetic approaches. The aim of our study was to determine the heritability of frequency and temporal resolution for auditory signals and speech recognition in noise in 96 identical or fraternal twin pairs, aged 6ā11 years. Measures of auditory processing (AP) of non-speech sounds included backward masking (temporal resolution), notched noise masking (spectral resolution), pure-tone frequency discrimination (temporal fine structure sensitivity), and nonsense syllable recognition in noise. We provide evidence of significant heritability, ranging from 0.32 to 0.74, for individual measures of these non-speech-based AP skills that are crucial for understanding spoken language. Identification of specific heritable AP traits such as these serve as a basis to pursue the genetic underpinnings of APD by identifying genetic variants associated with common AP disorders in children and adults
- ā¦