398 research outputs found
The Place of the Sacred in Cassirerâs Philosophy of Mythology
In this essay I defend Cassirerâs account of mythical culture against a series of critiques raised against his philosophy of mythology. Cassirer has been charged with neglecting the profane dimension of mythical culture and with presenting an inconsistent account of sacred being. In order to make headway on these critiques, I first demonstrate that Cassirer does in fact acknowledge the profane and its place in mythical culture. Through close conceptual and textual analysis, I reconstruct Cassirerâs account of the sacred and the profane in âMyth as Form of Intuitionâ in the second volume of the Philosophy of Symbolic Forms. After demonstrating the presence of this distinction in Cassirerâs texts, I reconstruct Cassirerâs account of the emotive origin of the sacred in mythical culture. Finally, I show how Cassirerâs the law of mythical culture is not inconsistent with the sacred, but is a further articulation of the form of sacred being
The âFacebook\u27 Effect: College Students\u27 Perceptions of Online Discussions in the Age of Social Networking
Despite the growing prominence of Facebook in the lives of college students, few studies have investigated the potential of these innovative web-based communication tools for engaging students in academic discussions. This study used a pre-test, post-test design in two introductory-level courses at a large public university to compare studentsâ (n = 107) perceptions of, attitudes toward, and perceived learning associated with two different online discussion tools: the Facebook group forum and a university-sponsored online tool. Although pre-course surveys indicated that few students enjoyed online discussions, postcourse analysis revealed significant changes in studentsâ opinions regarding the value and functionality of web-based discussion forums, with Facebook as their clear preference. Students who participated in Facebook discussions enjoyed the siteâs familiarity, navigability, and aesthetically appealing interface. Facebook users also reported that they were able to become better acquainted with classmates, felt like valued participants in the course, and learned more course material. This study suggests that, if used appropriately, Facebook may help to increase college student engagement in certain learning contexts by cultivating classroom community and stimulating intellectual discourse
Characterising white matter in Huntington's disease
Background:
Investigating early white matter (WM) change in Huntingtonâs Disease (HD) can improve our understanding of the way in which disease spreads from the striatum.
Objectives:
Here, we provide a detailed characterisation of pathology-related WM change in HD. We first examined WM microstructure using diffusion-weighted imaging, then investigated both underlying biological properties of WM and products of WM damage including iron, myelin plus neurofilament light (NfL), a biofluid marker of axonal degeneration â in parallel with the mutant huntingtin protein (mHTT).
Methods:
We examined WM change in HD gene-carriers from the HD-CSF cohort, baseline visit. We used standard diffusion MRI to measure metrics including fractional anisotropy (FA), a marker of WM integrity, and diffusivity; a novel diffusion model (NODDI) to measure axonal density and organisation; T1 and T2 weighted structural MRI images to derive proxy iron content and myelin-contrast measures; and biofluid concentrations of NfL (in CSF and plasma) and mHTT (in CSF).
Results:
HD gene-carriers displayed reduced FA and increased diffusivity compared to controls, both of which were also associated with disease progression, CSF and mHTT levels. HD gene-carriers also displayed proxy measures of reduced myelin-contrast and iron in the striatum.
Conclusion:
Collectively, these findings present a more complete characterisation of HD-related microstructural brain changes. Correlation between reduced FA, increased axonal orientation and biofluid markers suggest that axonal breakdown is associated with increased WM degeneration, while higher quantitative T2 signal and lower myelin-contrast may indicate a process of demyelination limited to the striatum
Evaluation of NV556, a Novel Cyclophilin Inhibitor, as a Potential Antifibrotic Compound for Liver Fibrosis
Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are peptidyl-prolyl cis-trans isomerases that facilitate protein folding and conformational changes affecting the function of the targeted proteins. Due to their activity, cyclophilins have been presented as key factors in several stages of the fibrotic process. In this study, we investigated the antifibrotic effects of NV556, a novel potent sanglifehrin-based cyclophilin inhibitor, in vitro and in vivo. NV556 potential antifibrotic effect was evaluated in two well-established animal models of NASH, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. We demonstrate that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFÎČ1-activated hepatic stellate cells in vitro. Taken together, these results present NV556 as a potential candidate for the treatment of liver fibrosis
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Semantic memory redux: an experimental test of hierarchical category representation
Four experiments investigated the classic issue in semantic memory of whether people organize categorical information in hierarchies and use inference to retrieve information from them, as proposed by Collins & Quillian (1969). Past evidence has focused on RT to confirm sentences such as âAll birds are animalsâ or âCanaries breathe.â However, confounding variables such as familiarity and associations between the terms have led to contradictory results. Our experiments avoided such problems by teaching subjects novel materials. Experiment 1 tested an implicit hierarchical structure in the features of a set of studied objects (e.g., all brown objects were large). Experiment 2 taught subjects nested categories of artificial bugs. In Experiment 3, subjects learned a tree structure of novel category hierarchies. In all three, the results differed from the predictions of the hierarchical inference model. In Experiment 4, subjects learned a hierarchy by means of paired associates of novel category names. Here we finally found the RT signature of hierarchical inference. We conclude that it is possible to store information in a hierarchy and retrieve it via inference, but it is difficult and avoided whenever possible. The results are more consistent with feature comparison models than hierarchical models of semantic memory
Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice
This article is available open access through the publisherâs website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero âinjected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftrâ/â mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the
Cystic Fibrosis Trust, and the Katharine Dormandy Trust
Quantum self-consistency of brane models
Continuing on our previous work, we consider a class of higher dimensional
brane models with the topology of , where
is a one-parameter compact manifold and two branes of codimension 1 are located
at the orbifold fixed points. We consider a set-up where such a solution arises
from Einstein-Yang-Mills theory and evaluate the one-loop effective potential
induced by gauge fields and by a generic bulk scalar field. We show that this
type of brane models resolves the gauge hierarchy between the Planck and
electroweak scales through redshift effects due to the warp factor . The value of is then fixed by minimizing the effective potential. We
find that, as in the Randall Sundrum case, the gauge field contribution to the
effective potential stabilises the hierarchy without fine-tuning as long as the
laplacian on has a zero eigenvalue. Scalar fields can
stabilise the hierarchy depending on the mass and the non-minimal coupling. We
also address the quantum self-consistency of the solution, showing that the
classical brane solution is not spoiled by quantum effects.Comment: 10 page
The âSolubleâ Adenylyl Cyclase in Sperm Mediates Multiple Signaling Events Required for Fertilization
SummaryMammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they âcapacitate,â i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these ârescuedâ null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC
The Dynamical Status of the Cluster of Galaxies 1E0657-56
We present the results of a new spectroscopic and photometric survey of the
hot X-ray cluster 1E0657-56, at z=0.296. We determine the presence of a low
velocity dispersion subcluster, which is offset from the main cluster position
by 0.7 Mpc and about 600 km/s. We determine the virial masses and total
luminosities of the cluster and its subcluster, and solve for the two-body
dynamical model. With additional constraints from the results of the analysis
of the cluster X-ray emission by Markevitch et al. (2001), we find that the
subcluster passed through the cluster centre about 0.15 Gyr ago. Taken at face
value the mass of the subcluster is typical of a loose group. It is however
difficult to establish the pre-merger mass of the colliding system. We provide
tentative evidence that the subcluster is in fact the remnant core of a
moderately massive cluster, stripped by the collision with 1E0657-56. The main
cluster dynamics does not seem to have suffered from this collision. On the
contrary, the cluster X-ray properties seem to have been significantly
affected. We also discuss the effect of the subcluster collision in relation to
starburst events and the cluster radio halo.Comment: Accepted for publication on A&
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